WUSTL School of Medicine News

X Prize to provide incentive for Alzheimer’s cure

Michael C. Purdy — 2013-05-23 00:00:00

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Washington University neurosurgeon Eric Leuthardt, left, and preventive medicine expert Dean Ornish make their pitch for Alzheimer’s to be the focus of a new X Prize. Their winning efforts will lead to a $50 million incentive for researchers worldwide to find a cure for the devastating disease.

The X Prize Foundation, which in 2004 awarded $10 million for the first privately built, manned spacecraft launched into space twice in two weeks, has now set its sights on effective treatment for Alzheimer’s disease.

The foundation is creating a new Alzheimer’s X Prize to inspire the ingenuity of researchers and increase their interest in taking on the daunting task of stopping the disease.

The new prize was proposed by a team of experts co-directed by Eric C. Leuthardt, MD, associate professor of neurological surgery and biomedical engineering at Washington University School of Medicine in St. Louis. The team’s proposal to tackle Alzheimer's won a competition that drew proposals on topics of importance to society. As a result, the foundation is now raising $50 million to establish the Alzheimer’s X Prize.

Leuthardt

“Basically, X Prizes are about making the impossible possible,” said Leuthardt, who treats patients at Barnes-Jewish Hospital and St. Louis Children's Hospital. “They’re about giving innovators the incentive to achieve new breakthroughs that benefit society.”

A similar contest, known as the Orteig Prize, inspired Charles Lindbergh’s solo flight across the Atlantic Ocean in 1927, Leuthardt noted, and that led to the start of commercial air travel a short time later.

The X Prize Foundation hosts an annual “visioneering” conference, where more than 100 pioneering scientists, inventors, engineers, artists and business leaders meet to propose new X Prizes as part of a competition.

The attendees are divided into teams and assigned an area of research within which they create an X Prize proposal. The team led by Leuthardt and Dean Ornish, MD, founder and president of the non-profit Preventive Medicine Research Institute and clinical professor of medicine at the University of California, San Francisco, was given the topic of aging.

Noting that an epidemic of Alzheimer’s disease is on its way, the team compared the potential crisis to a meteor in space lined up to strike the Earth.

“Populations are growing older around the world, and Alzheimer’s risk increases significantly with age,” Leuthardt said. “This will affect not only the elderly but also their families and loved ones, and it will have devastating emotional and economic consequences.”

The details of what qualifies as a cure for Alzheimer’s will be established as the foundation raises the $50 million prize. As in other X Prizes, the winners of the new award will retain the intellectual property rights for their breakthrough.

“I think everyone is touched or will soon be touched by Alzheimer’s,” Leuthardt said. “I think that’s part of the reason why our proposal won — everybody in the audience had a family member affected by Alzheimer’s or knew someone with a family member affected by this disorder.”

Other X Prizes include or have included a prize for the first “tricorder” (a handheld device that can non-invasively diagnose 20 diseases like the tricorders featured on Star Trek); a prize for the first group to sequence the DNA of 100 100-year-olds for identification of genetic factors linked to extended lifespans; and a prize for the first privately funded team to send a lander to the moon.

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

African-American health and well-being subject of new study in St. Louis area

Leslie Gibson McCarthy — 2013-05-22 00:00:00

A new comprehensive, multi-disciplinary study on the health and well-being of African Americans in St. Louis could have significant local impact.

The research findings and a series of related policy briefs will culminate in a community conference in 2014, coinciding with the 60th anniversary of Brown v. Board of Education and the 50th anniversary of the Civil Rights Act of 1964.

The project is funded by the Missouri Foundation for Health and includes faculty from Washington University in St. Louis and from Saint Louis University. WUSTL's Institute for Public Health, the Brown School’s Policy Forum, and the St. Louis American are partners as well.

Purnell

“This is unprecedented in that it will focus not only on the health issues of African Americans, but also education and economics,” says Jason Q. Purnell, PhD, assistant professor at the Brown School and lead researcher on the project.

“African Americans bear a considerable burden of disease, disability and death in the St. Louis region,” Purnell says. “The goal with this project is to produce a series of policy briefs and a report that will identify the issues and offer real solutions.”

The research will focus on African Americans in the City of St. Louis and in St. Louis County. Policy briefs will be prepared in five areas:

A Multi-Sector Approach to Health Disparities in St. Louis
African American Educational Attainment and Health in St. Louis
Mental Health’s Impact on Education, Employment, and Physical Health among African Americans in St. Louis
Racial Composition of the St. Louis Region and the Association with Health
Addressing Risk Factors for Chronic Disease in African Americans in St. Louis

“Several important recent reports on health have included a focus on African Americans in St. Louis, but much of the emphasis has been on access to health care,” Purnell says. “We’re looking to broaden our focus to include the reasons there is such need for expanded health care access in the community.”

To do the research, Purnell assembled a team of African-American scholars that cuts across disciplines and institutions.

“We’re going to need all hands on deck to get things done,” Purnell says. “That’s another key to what we’re doing: Change is going to require a multi-sector approach – business, education, government, and non-profit organizations.

“Everyone’s going to have to be part of the process.”

The participating scholars from Washington University, in addition to Purnell, are:

Bettina F. Drake, PhD, assistant professor of surgery in Public Health Sciences at the School of Medicine;

Melody S. Goodman, PhD, assistant professor of surgery in Public Health Sciences at the School of Medicine;

Darrell L. Hudson, PhD, assistant professor at the Brown School; and

William F. Tate, PhD, the Edward Mallinckrodt Distinguished University Professor in Arts & Sciences and chair of the Department of Education.

Saint Louis University faculty partners are:

Keith Elder, PhD, associate professor and chair, Department of Health Management & Policy for the College for Public Health & Social Justice; and

Keon Gilbert, DPhil, assistant professor at the College for Public Health & Social Justice.

A Community Partner Group with representatives from key sectors in the region is being formed to advise the scholars on the policy briefs and the final report.

Better detection for elephantiasis worm infection

Caroline Arbanas — 2013-05-20 00:00:00

Washington University School of Medicine

Washington University's Kurt Curtis, in Liberia, readies a new diagnostic test for lymphatic filariasis, a mosquito-born infection that can lead to enormously swollen limbs and genitals. The new test detected the infection in many people that the standard test had missed.

A new diagnostic test for a worm infection that can lead to severe enlargement and deformities of the legs and genitals is far more sensitive than the currently used test, according to results of a field study in Liberia, in West Africa, where the infection is endemic.

The new test found evidence of the infection – lymphatic filariasis – in many more people that the standard test had missed.

The study, the first to independently evaluate the new test, was led by researchers at Washington University School of Medicine in St. Louis and funded by the Bill & Melinda Gates Foundation.

The infection affects 120 million people living in 73 countries, leaving some 40 million profoundly disfigured and incapacitated. Both tests detect the presence of worms that cause lymphatic filariasis, a devastating mosquito-borne illness also known as elephantiasis.

But the new test has significant advantages over the test that has been used for more than a decade not only to diagnose the disease, but to map, monitor and evaluate the success of a massive global public health program aimed at completely eliminating the disease by 2020.

Results of the study are published May 20 in The American Journal of Tropical Medicine and Hygiene.

“The older test has had a major impact, but the new one is even better,” says lead author Gary J. Weil, MD, an infectious diseases specialist at Washington University School of Medine. “Annually, medication to treat and prevent the infection is distributed to more than 500 million people worldwide. The improved sensitivity of the new test will help determine whether the mass treatment program has been effective and also identify regions that need additional attention.”

An accompanying editorial by Maria Rebollo, MD, and Moses Bockarie, PhD, at the Centre for Neglected Tropical Diseases in the United Kingdom says the new diagnostic test “represents a major breakthrough for rapid diagnosis of lymphatic filariasis in the blood.”

The new test also has a longer shelf life, estimated at two years without refrigeration, compared with three months for the older version, and is expected to cost less.

Weil’s research team worked with colleagues at the Liberian Institute for Medical Research to conduct a side-by-side comparison of the new test strip and the currently used test. They evaluated the tests in 503 people ranging in age from 6 to 89.

Both versions of the test are manufactured by Alere Scarborough Inc. of Maine and detect the presence in the blood of a protein produced by the worm parasite Wuchereria bancrofti that causes lymphatic filariasis. The new test is performed by pricking the finger and placing a person’s blood onto the test strip, which looks similar to an over-the-counter pregnancy test. Like many pregnancy tests, the lymphatic filariasis test is positive if two lines appear in the test window and negative if only one line shows.

The study's results show that the new test is highly sensitive, detecting nearly 26 percent more infections of lymphatic filariasis than the standard test (124/503 infections vs. 98/503 infections). The new test also was easier to perform and results were easier to read.

“This gives us some indication of the numbers of infections we were missing with the older test,” Weil says. “On a global scale, it’s a huge number of cases. We need to have an accurate test to be sure we are reaching all the people who have the disease or are at risk of developing it.”

Worldwide, some 1.4 billion people are at risk of lymphatic filariasis, which is endemic in many countries in Africa, Southeast Asia and other tropical regions. Worm larvae deposited by the bite of an infected mosquito enter the body and migrate to the lymphatic system, where they mature into adult worms.

The thread-like parasitic worms can live and reproduce in the body for years. Ultimately, this damages the lymphatic vessels that drain fluid from the tissues and causes the enormous swelling and disabling deformity of the legs and in males, the scrotum.

Weil has been active for years in efforts to eliminate lymphatic filariasis via mass drug administration, an approach that involves giving antifilarial drugs to everyone in areas with high infection rates. Organizers of the Global Programme to Eliminate Lymphatic Filariasis, launched in 2000, coordinate periodic, repeated mass drug administration of antifilarial medications to more than 500 million people annually, making it the world’s largest public health intervention program based on mass drug administration.

The research is funded by the Bill & Melinda Gates Foundation.

Weil GJ, Curtis KC, Fischer K, Majewski AC, Fischer PU, Fakoli L, Gankpala L, Bolay FK, Lammie P, Pelletreau S and Won KY. Laboratory and field evaluation of a new rapid test for detecting Wuchereria bancrofti antigen in human blood. American Journal of Tropical Medicine and Hygiene. May 20, 2013.

Bear Cub grants foster entrepreneurship

Caroline Arbanas — 2013-05-16 00:00:00

Joe Angeles

Jung-Tsung Shen, PhD, is one of five WUSTL scientists recently awarded a Bear Cub grant. Shen is developing a photonic switch, pictured on his computer screen, that is much faster, smaller and more energy efficient than other switches now used to support broadband communications.

Scientists are natural problem solvers, full of innovative ideas. But moving those ideas from the laboratory to the marketplace can be difficult, even for those with an entrepreneurial bent.

In part, that’s because federal research dollars typically don’t support the proof-of-concept studies needed to demonstrate the feasibility of a promising new technology or diagnostic test. And while most scientists feel right at home in the laboratory, they often struggle to develop a successful pitch or execute a business plan.

To fill the gap, Washington University’s Bear Cub program provides university scientists with funding to help commercialize their discoveries. Beginning this year, scientists who are funded through the program also have access to business mentors and other hands-on assistance to develop their technologies.

“We want our faculty and students to have every opportunity to commercialize their technologies,” says Bradley Castanho, PhD, director of the university’s Office of Technology Management. “Part of that means creating an atmosphere where scientists are supported and encouraged in their efforts to become entrepreneurs, while also helping to make funding available so they can move their discoveries beyond the lab.”

The university recently announced a new round of Bear Cub funding, with $204,000 going to five scientists:

David Beebe, PhD, the Janet and Bernard Becker Professor of Ophthalmology and Visual Sciences, is developing a way to prevent the formation of cataracts in patients undergoing retinal surgery. To repair the retina, surgeons must remove a portion of the vitreous gel that fills the eye, a process that exposes the lens to oxygen and increases the likelihood of cataracts.

Working with colleagues at Purdue University who developed a novel biological polymer, Beebe will evaluate whether the polymer can preserve the remaining vitreous gel and restore its properties to prevent cataracts from forming. He is now proposing to test the polymer in animal models, with the goal of developing a sterile synthetic polymer powder that could be mixed with sterile saline and infused into the eye at the end of retina surgery. Annually, some 300,000 patients in the U.S. alone could benefit from the technology, the researchers have estimated.

Joseph Gaut, MD, PhD, assistant professor of pathology and immunology, has developed a test for the early detection of acute kidney injury, a complication that can occur in critically ill patients and in those undergoing heart bypass surgery. Some 700,000 U.S. patients undergo heart bypass surgery every year, and one-fourth of them develop kidney damage, which leads to longer hospital stays and deaths, in some cases.

The test developed by Gaut and his colleagues is based on a kidney-specific protein that is elevated in the blood soon after acute kidney damage occurs, typically several days before currently available tests. The researchers will evaluate whether the protein can accurately diagnose early kidney damage in animal models and in heart bypass patients, which would enable earlier treatment.

Michael S. Hughes, PhD, research associate professor of medicine, is working with John E. McCarthy, PhD, the Spencer T. Olin Professor of Mathematics, and Samuel A. Wickline, MD, professor of medicine, to develop an imaging technology that captures certain aspects of electromagnetic and acoustic waves and converts that information into an image.

Rather than being based on wave energy, however, the image measures the entropy, or disorder, in an object and can detect features that are not picked up by ultrasound, CT scans and other conventional imaging. Entropy imaging could potentially have wide applications in medicine and be used to identify defects in materials used by the aerospace and other transportation industries or in heavy manufacturing. Another possible application is in security scanning to detect potential threats and in remote surveillance.

Eric Leuthardt, MD, associate professor of neurological surgery, has designed a monitor to noninvasively detect obstructions in vascular grafts and shunts. The monitor uses a nanoscale flow sensor that can be integrated into an implantable shunt or graft. Both can narrow over time and become obstructed, leading to life-threatening complications.

For example, about one in 500 babies is born with hydrocephalus, a buildup of fluid on the brain. It is most often treated surgically by inserting a shunt that diverts the fluid to another area of the body. But symptoms of pain in the head, even something like a headache, can lead doctors to order CT scans, nuclear medicine studies and sometimes exploratory surgery to determine whether the pain is related to an obstruction.

The sensor Leuthardt has developed can be activated by light to measure the flow rate of fluids through grafts and shunts, and he plans to test the device in animal models.

Jung-Tsung Shen, PhD, assistant professor of electrical and systems engineering, has developed a photonic switch that is orders of magnitude faster, smaller and more energy efficient than other switches typically used to support the information superhighway. In the future, demands for broadband signal transmission and processing will require ultra-fast and extremely low-energy optical switching and modulation rates that aren’t possible with current approaches.

The switch designed by Shen and his colleagues uses artificially engineered materials, called metamaterials, that exhibit exceptional optical properties not easily observed in nature. In addition to telecommunications, the switch also could be used in high-resolution medical imaging and in semiconductor manufacturing. Bear Cub funding will allow Shen to further develop and test the switch.

Washington People: Catherine Appleton

Jim Goodwin — 2013-05-15 00:00:00

Robert Boston

Catherine “Kate” Appleton, MD, reads film from a mammogram. She says one of the toughest parts of being a radiologist is having to diagnose breast cancer in young women. “But what might surprise people is that, more often than not, we actually give good news here,” she said. “Most people who walk through the door leave with good news.”

Taka Yanagimoto

Appleton and her children, Lily, 8, and Mack, 6, tend to their two new chickens.

Catherine “Kate” Appleton, MD, is assistant professor of radiology and chief of breast imaging at the Mallinckrodt Institute of Radiology. Last year, she and her colleagues evaluated and cared for more than 30,000 women who came to the Joanne Knight Breast Health Center for screening, diagnostic evaluation and image-guided breast procedures.

You received your medical degree with research honors from the University of Florida in 2000. What motivated you to study medicine?

My mom is a nurse, and growing up I was always impressed with her ability to care for us. She always knew what to do to make me feel better. Early on, I had a strong interest in science, and I blended that with what I saw my mom doing – caring for people. She very much encouraged me to pursue my interest in science, and that led to a career in medicine.

Last year, you were appointed chief of breast imaging and director of the breast radiology service at age 36. What advice would you offer others pursuing an accelerated career path in medicine?

I started medical school when I was 20, as part of a seven-year combined undergraduate/medical school program at the University of Florida, so I was accelerated on the front end. I think whether you’re on a traditional track, a fast track or your own track, it’s important to talk with and spend time with physicians. As early as high school, I shadowed physicians and volunteered at our local hospital. I asked questions. Those things helped me solidify my interests early on, so that I could make a decision to enter an accelerated program. Exposure to the various fields within medicine is important so you can appreciate the diverse opportunities medicine affords. My career as a breast-imaging radiologist is very different than many other medical specialties, in terms of my day-to-day work. I think doing your homework and putting in the time is really important.

Were you interested in other types of medicine, or did you always know you would be doing what you are now?

Entering medical school, I was actually really interested in forensic pathology. However, during my clinical rotations, I quickly decided I wanted to interact with patients and their families. I was a medical student who loved almost every rotation; the great thing about radiology was that you interfaced with physicians across the board. That aspect sparked my initial interest in radiology. Then, in my radiology residency here at Barnes-Jewish Hospital and Washington University School of Medicine, I rotated through breast imaging. Unlike some parts of radiology in which you can be a step or two removed from patient care, there is patient interaction on a daily basis in breast imaging. I had missed that and felt this was a good fit for me. And, of course, meeting Dr. Barbara Monsees, who is my mentor and the former chief of breast imaging, really helped solidify that this is what I was meant to do.

What sort of mentoring are you a part of?

I mentor our residents and fellows formally and informally. I’ve had medical school and undergraduate students approach me, and I do my best to mentor them on an individual basis, as well. And I still consider myself a mentee, so I continue to be mentored by some very generous people in the medical center and across the country.

What other details can you share about being a mentee?

Certainly, this transition into chief of breast imaging was monumental for me. I sought out the advice and counsel of other leaders in the department and medical school, as well as contacts I have across the country. I thought it would be valuable to learn from their experiences — where they think they took a positive step or where they wish they would have done something differently.

Have you found that being a mentee helps you be a better mentor?

Absolutely. I think once you have been mentored by multiple people, you can distill what advice was more salient. I think as a mentor you need to look at individual mentees, and their big picture, because your personal anecdotes are one thing, but working within a system will have different implications for different people. One size doesn’t fit all.

What do you find most challenging about your job?

The most challenging thing is to tell a very young patient that she has breast cancer. Young patients in their 20s and early 30s are more often blindsided by the diagnosis, and it’s very difficult. But what might surprise people is that more often than not, we actually give good news here. Most people who walk through the door leave with good news.

What research projects are you working on?

One of the awesome things about being at Washington University is the tremendous potential for collaboration, and I’ve taken advantage of that potential. I’m working with professors Lihong Wang and Mark Anastasio in the School of Engineering & Applied Science on some very exciting projects. I bring the clinical perspective, and they bring the technical development and expertise, so it’s fantastic translational research. The project with Professor Wang involves photoacoustic imaging of sentinel lymph nodes in breast cancer patients. In addition, in the breast center, I collaborate with multiple colleagues, including Dr. Julie Margenthaler and my fellow breast imagers. Our section is completing some novel projects involving breast tomosynthesis, the so-called “3-D mammogram.”

Regarding my personal projects, I am currently working on an analysis of decision fatigue in mammography interpretation. After an article was published about judicial decision fatigue some time ago, I started wondering, “Do I do a better job of reading a mammogram early in the day, before lunch, after lunch or late in the day?” So I’m looking at our decisiveness in mammography interpretation, based on the time of day. I want to see if there’s a tipping point where you reach decision fatigue.

What should everyone know about breast cancer?

Women should get a mammogram once per year starting at age 40 if they are at average risk for breast cancer. But guidelines change, so it’s important to stay current and speak to your health-care provider, or call us, and we can advise patients on what they need to do. High-risk patients, including those with a family history, should be assertive about getting the care they need. Treatments continue to improve, outcomes continue to improve, but early diagnosis is key. Get your mammogram.

Almost everyone has been affected by cancer. Outside of your medical practice, how have you been affected?

Like many people, I’ve had family members affected by cancer including, most recently, someone diagnosed with breast cancer. There are so many chronic illnesses that people face, and I think whether it’s cancer or another disease, a physician’s personal and family experiences foster empathy for patients that translate across multiple ailments. For me, those experiences have definitely made me a more sympathetic and more empathetic physician.

How so?

It’s tough to be a patient. It’s tough not to know what happens next – it’s frightening. So I always have in mind, as I’m telling a patient bad news on, potentially, the worst day of her life, she will probably remember exactly what I say for the rest of her life. I want to get it right, say the right thing in the right way. Being a patient and being the family member of a patient, myself, has made me a better listener. Being a parent has also made me a better listener.

Talk about your children and how they’ve affected how you practice medicine.

Lily is 8, and Mack is 6. I think any parent knows that it’s the most difficult job in the world, but it’s also the very best and most rewarding. My children, more than anything, have taught me patience, and that translates to being a better listener, slowing down and taking greater care and time with patients.

How difficult is it balancing your professional and personal responsibilities?

It’s always a juggle. My children know that I take my job very seriously, and I think it’s important that I model that for them. They know that when I go to work, I take care of people, and they are proud of that, I think. However, I believe at the end of the day Lily and Mack know they are my very first priority. And we also have very interesting dinner conversation! My children know a lot about what I do; it’s just part of the fabric of our home life. I spend as much of my free time with my children as I can, and they know they’re No. 1.

What are some favorite family activities that help you recharge?

We love to be outside in our yard, play ball with the kids or go on the swing set. We have two big dogs to play with. And, we actually just got two chickens. I love animals, so that’s been a fun turn of events.

Tell us more about the chickens. Did your children ask for them?

Oh no, that was my crazy idea. My husband is a great sport. After almost a year, I finally wore him down, and right after Easter we got two chickens. It’s been an interesting education in poultry.

I have an organic garden, and I just thought that they dovetailed very nicely with my garden. The kids are learning a lot about where their food comes from, and it’s just an interesting and fun family activity.

Any other hobbies?

I have accumulated them throughout my life. The piano is a holdover from my childhood, and I wanted music to be a part of my kids’ lives. And I like to be active, so having pets and a garden and doing sports are all things to keep my children and me active and engaged. We ice skate together. I play tennis, terribly, but I have fun. I’m not sure I would exactly ascribe to the “work-hard, play-hard” philosophy, but I do think life is made to be enjoyed, and so I’m trying out different things. I took a knitting class last fall because I thought, “I’ll try that,” but it wasn’t for me.

Tell us more about your chicken-averse husband.

His name is Taka Yanagimoto, and he is the photography coordinator for the Cardinals, and he’s awesome. He’s fun, and he makes me laugh all the time. And like I said, he’s a good sport. Anybody who lets me get two chickens is a good sport.

Morris receives top Alzheimer’s Association honor

Michael C. Purdy — 2013-05-15 00:00:00

Washington University neurologist John C. Morris, MD, received the Alzheimer’s Association’s Medical and Scientific Award for 2013.

Morris

Morris, the Harvey A. and Dorismae Hacker Friedman Distinguished Professor of Neurology and director of the Charles F. and Joanne Knight Alzheimer’s Disease Research Center (Knight ADRC), was recognized for his many contributions to Alzheimer’s research and treatment at the association’s annual Rita Hayworth Gala in Chicago May 11.

The gala is named in honor of actress Rita Hayworth, who died of Alzheimer’s disease. The actress’s daughter, Princess Yasmin Aga Khan, started the tradition of the galas in 1984, and they have raised more than $59 million for Alzheimer’s research.

“We’ve had a long and highly valued relationship with the Alzheimer’s Association,” Morris said. “Receiving this award was a moving and very meaningful honor for me and all of my colleagues at the Knight ADRC.”

Among other accomplishments, Morris’ research team refined the Clinical Dementia Rating (CDR) system, which was first developed by the founding director of the Alzheimer’s center, Leonard Berg, MD. The CDR now is the standard clinical measure for staging of dementia. Morris’ studies have helped clinicians better distinguish between the normal effects of aging on memory and the earliest clinical symptoms of Alzheimer’s disease.

Over the course of his career, Morris has helped guide the formation of a new consensus that Alzheimer’s disease actively damages patients’ brains for a decade or more before mental functions become noticeably impaired. Morris, Joseph L. Price, PhD, DPhil, professor of anatomy and neurobiology, and others at the ADRC contributed significantly to this consensus through a series of studies that revealed widespread brain damage in patients only recently diagnosed with Alzheimer’s.

This insight led scientists to conclude that treating Alzheimer’s disease prior to cognitive impairment might significantly improve the chances of slowing or stopping the breakdown of normal brain function. Morris and his colleagues at the Knight ADRC have been frontrunners in the development of biomarkers, or factors that can be tested to identify the presence of presymptomatic Alzheimer’s disease.

“I accept this award on behalf of the investigators, staff, and participants and their families of the Knight ADRC, who together are responsible for the accomplishments this award recognizes,” Morris said.

In 2008, the National Institute on Aging named Morris as principal investigator of the Dominantly Inherited Alzheimer’s Network (DIAN), an international collaboration of Alzheimer’s research centers. DIAN allowed researchers to validate Alzheimer’s biomarkers in patients with rare inherited forms of the disease.

Based on the groundwork laid by Morris, researchers now are testing preclinical treatment of inherited forms of Alzheimer’s disease in a second international research collaborative, the Dominantly Inherited Alzheimer’s Network Trials Unit, which is led by Randall Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor in Neurology at Washington University.

National Bike to Work Day is May 17

2013-05-16 00:00:00

Elizabethe Holland Durando

Laura Bierut, MD, professor of psychiatry, and Brad Evanoff, MD, the Richard and Elizabeth Henby Sutter Professor of Occupational and Environmental Medicine, have been cycling to work at the School of Medicine for almost 20 years. The commute from the couple's University City home is a little less than five miles. They encourage other employees to join them on National Bike to Work Day, which is Friday, May 17. For information about Bike to Work Day and commuting tips, click here.

I-CARES announces 2013 funded research projects

2013-05-14 00:00:00

The International Center for Advanced Renewable Energy and Sustainability (I-CARES) has announced the award winners for its 2013 Call for Proposals.

As part of its mission, I-CARES awards seed funding to WUSTL faculty undertaking innovative and collaborative research in the broad areas of renewable energy and sustainability through an annual call for proposals.

This year, special emphasis was placed on projects related to climate change.

I-CARES has awarded 12 projects with 25 Washington University faculty from five schools: Arts & Sciences, the George Warren Brown School of Social Work, the School of Engineering & Applied Science, the Sam Fox School of Design & Visual Arts and the School of Medicine.

For a full list of winning projects and the faculty members involved, visit icares.wustl.edu/research/Pages/default.aspx.

I-CARES supports a network of national and international researchers all with a focus on renewable energy, the environment and sustainability, extending beyond Washington University’s seven schools. With the addition of the 2013 research awardees, I-CARES now supports 99 individual researchers across 71 projects.

Three doctoral candidates named Bouchet Fellows

2013-05-15 00:00:00

Three doctoral candidates at Washington University in St. Louis were inducted into the Edward A. Bouchet Graduate Honor Society at the annual Bouchet Conference on Diversity in Graduate Education April 19-20 at Yale University.

Inducted as the seventh class of WUSTL Bouchet Fellows are Stephanie N. Rodriguez, a doctoral candidate in the immunology program in the Division of Biology and Biomedical Sciences; Beverly A. Tsacoyianis, a doctoral candidate in the Department of History in Arts & Sciences; and Sha-Lai L. Williams, who will be conferred a PhD from the Brown School during the university’s May 17 Commencement.

The Bouchet Society, named for the first African American to earn a doctorate in the United States, recognizes outstanding scholarly achievement and promotes diversity and excellence in doctoral education and the professoriate.

The society seeks to develop a network of preeminent scholars who exemplify academic and personal excellence, and serve as examples of scholarship, leadership, character, service and advocacy for students who have been traditionally underrepresented in the academy.

Rafia Zafar, PhD, associate dean for diversity and inclusiveness in the Graduate School of Arts & Sciences, coordinates the WUSTL chapter of the Bouchet Society.

“Washington University’s graduate students are known to be among the best in America; our Bouchet honorees take their place among the ranks of the highest achieving doctoral candidates in the nation,” Zafar said.

Rodriguez

Rodriguez, who works in the laboratory of Paul M. Allen, PhD, the Robert L. Kroc Professor of Pathology and Immunology, studies the intricate mechanisms of T cell development and how these important immune cells mediate protection to pathogens.

Using a novel CD4 T cell system unique to Allen’s laboratory, her dissertation work investigates the dependence of CD4 T cells on self-molecules for their development into functionally mature and self-tolerant mediators of immune protection, and for continued survival in this mature state.

Her research will address longstanding questions in the field of CD4 T cell development, including the timing, number and duration of immature T cell interactions with cells presenting self-molecules, as well as directly assessing the controversial role of self-molecules in the maintenance of mature CD4 T cells.

The recipient of a National Science Foundation Graduate Research Fellowship, Rodriguez has co-authored an article in the Journal of Immunology.

She is director of WUSTL’s Young Scientist Program, which was created in 1991 by medical and graduate students to attract high school students from disadvantaged backgrounds into scientific careers through activities emphasizing hands-on research and interaction between young people and scientists.

She has been involved with the organization since 2009 when she joined as a mentor and tutor.

Rodriguez earned a bachelor’s degree in biology with honors in microbes and immunity from Stanford University in 2009.

Tsacoyianis

Tsacoyianis, a Chancellor’s Graduate Fellow, is completing her dissertation, “Making Healthy Minds and Bodies in Syria, 1903-1961.”

She studies the social and medical history of mental illness in 20th-century Syria, arguing that psychiatrists in Syria presented mental health treatment to Syrians as more than a way to control or cure mental illness, but as a modernizing worldview to suppress and delegitimize spirit-based vernacular treatment.

Her work contributes to scholarly debates in the history of medicine, particularly in the role of religion and science in healing, and debates about the role of the state and various non-state actors in preserving health and shaping the bodies and minds of citizens.

Tsacoyianis has received numerous honors, including a Fulbright-Hays Doctoral Dissertation Research Abroad fellowship and a P.E.O. Scholar award.

She is the book review editor for the Syrian Studies Association, an interdisciplinary, international organization, and speaks and reads multiple languages, including Spanish, French, Hebrew and Arabic.

Through the IIE Scholar Rescue Fund, she also has actively worked to secure safe academic positions for international scholars at risk for discrimination and/or political unrest in their home countries.

Tsacoyianis earned a bachelor’s degree in Near Eastern and Judaic studies with a minor in Islamic and Middle Eastern studies from Brandeis University in 2004. She will start a tenure-track position in Middle Eastern history at the University of Memphis this fall after earning a doctorate in August.

Williams

Williams earned a bachelor’s of social work in 1995 from North Carolina State University and a master’s of social work in 1996 from the University of North Carolina at Chapel Hill.

She was a licensed clinical social worker for more than 10 years and a supervisor to provisionally licensed clinical social workers in North Carolina for three years.

Her dissertation, “Mental Health Service Utilization Rates Among African-American Emerging Adults,” draws on her research in cultural competence among social work and helping professionals and racial/ethnic disparities in access to and use of quality mental health services.

A Chancellor’s Graduate Fellow, Williams also has received a pre-doctoral fellowship from the National Institute of Mental Health under the auspices of its training grant program.

She has co-authored articles in Perspectives on Social Work, Health Promotion Practice and Patient Education and Counseling.

Williams, an ordained evangelist, has volunteered as a youth and young adult counselor with the New Destiny Apostolic Church in Maplewood, Mo., since 2009.

She will join the School of Social Work at the University of Missouri-St Louis as a tenure-track assistant professor in the fall.

About the Bouchet Society

Yale and Howard universities established the Bouchet Society in 2005 to recognize the life and academic contributions of Edward Alexander Bouchet, the first African American to earn a doctorate from an American university.

Bouchet was the sixth person in the Western Hemisphere to be awarded the PhD in physics, which he earned from Yale in 1876. He also earned an undergraduate degree from Yale in 1874 and was elected to Phi Beta Kappa.

WUSTL was invited to become a Bouchet chapter member in 2007, joining Georgetown and Cornell universities and the universities of Michigan and Washington, among other peer institutions.

A WUSTL committee selected the university’s latest class of Bouchet Fellows. Members of the committee are: Zafar; Adrienne D. Davis, JD, vice provost and the William M. Van Cleve Professor of Law; and Elaine P. Berland, PhD, associate dean of the Graduate School of Arts & Sciences and director of the Liberman Graduate Center.

Alzheimer’s markers predict start of mental decline

Michael C. Purdy — 2013-05-13 00:00:00

Scientists at Washington University School of Medicine in St. Louis have helped identify many of the biomarkers for Alzheimer’s disease that could potentially predict which patients will develop the disorder later in life. Now, studying spinal fluid samples and health data from 201 research participants at the Charles F. and Joanne Knight Alzheimer’s Disease Research Center, the researchers have shown the markers are accurate predictors of Alzheimer’s years before symptoms develop.

Roe

“We wanted to see if one marker was better than the other in predicting which of our participants would get cognitive impairment and when they would get it,” said Catherine Roe, PhD, research assistant professor of neurology. “We found no differences in the accuracy of the biomarkers."

The study, supported in part by the National Institute on Aging, appears in Neurology.

The researchers evaluated markers such as the buildup of amyloid plaques in the brain, newly visible thanks to an imaging agent developed in the last decade; levels of various proteins in the cerebrospinal fluid, such as the amyloid fragments that are the principal ingredient of brain plaques; and the ratios of one protein to another in the cerebrospinal fluid, such as different forms of the brain cell structural protein tau.

The markers were studied in volunteers whose ages ranged from 45 to 88. On average, the data available on study participants spanned four years, with the longest recorded over 7.5 years.

The researchers found that all of the markers were equally good at identifying subjects who were likely to develop cognitive problems and at predicting how soon they would become noticeably impaired.

Next, the scientists paired the biomarkers data with demographic information, testing to see if sex, age, race, education and other factors could improve their predictions.

“Sex, age and race all helped to predict who would develop cognitive impairment,” Roe said. “Older participants, men and African Americans were more likely to become cognitively impaired than those who were younger, female and Caucasian.”

Roe described the findings as providing more evidence that scientists can detect Alzheimer’s disease years before memory loss and cognitive decline become apparent.

“We can better predict future cognitive impairment when we combine biomarkers with patient characteristics,” she said. “Knowing how accurate biomarkers are is important if we are going to some day be able to treat Alzheimer’s before symptoms and slow or prevent the disease.”

Clinical trials are already under way at Washington University and elsewhere to determine if treatments prior to symptoms can prevent or delay inherited forms of Alzheimer’s disease. Reliable biomarkers for Alzheimer’s should one day make it possible to test the most successful treatments in the much more common sporadic forms of Alzheimer’s.

Funding for this study was provided by the Longer Life Foundation; the National Institute of Neurological Disorders and Stroke (P30 NS057105); the National Institute on Aging (P50 AG005681, P01 AG003991, and P01 AG026276); Fred Simmons and Olga Mohan, and the Charles and Joanne Knight Alzheimer’s Research Initiative of the Washington University Knight Alzheimer’s Disease Research Center.

Roe CM, Fagan AM, Grant EA, et. al. Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later. Neurology, DOI 10.1212/WNL.0b013e3182918ca6

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Siteman's Komen St. Louis Race for the Cure team makes great strides against breast cancer

Jim Goodwin — 2013-05-14 00:00:00

The 15th Annual Komen St. Louis Race for the Cure in downtown St. Louis will be June 15. Since 1998, when the event first took place in St. Louis, Komen has awarded about $28 million for outreach, education, screening and research programs at Washington University Medical Center.

As someone affected by breast cancer, Yulanda Tomlin-Watson is part of a team no one chooses to join. In 1998, the disease took her mother, the nucleus of her extended family.

In her honor, Tomlin-Watson started a team the next year that friends and relatives happily joined. “JoAnn’s Jewels,” named after the woman they lost, has participated in the Komen St. Louis Race for the Cure every year since.

“My mom was the heart of our family,” Tomlin-Watson said. “She drew everyone together. That was just her spirit.”

Tomlin-Watson, an asthma coach at St. Louis Children’s Hospital, will continue the tradition June 15, when she joins the Siteman Cancer Center for the 15th Annual Komen St. Louis Race for the Cure in downtown St. Louis.

“Breast cancer is going to affect you some way – you, someone you know,” said Tomlin-Watson, whose group is a Siteman subteam. “We need to do what we can and to be more aware.”

Since 1998, when the Komen St. Louis Race for the Cure began, Susan G. Komen has awarded about $28 million for outreach, education, screening and research programs at Washington University Medical Center, said Susan Kraenzle, RN. She is manager of the Joanne Knight Breast Health Center at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

"It moves me to see our city turns out the way it does,” Kraenzle said. “I lost a sister to breast cancer, and I wish she were here to see this and know people are fighting for her and her kids.”

Courtesy of Yulanda Tomlin-Watson

The JoAnn's Jewels team, shown above, takes part in the Komen St. Louis Race for the Cure each year. Yulanda Tomlin-Watson, back row center, an asthma coach at St. Louis Children's Hospital, lost her mother to breast cancer.

Of the net proceeds raised locally, up to 75 percent stays in St. Louis to help Siteman Cancer Center and other organizations provide breast cancer education, screening and treatment programs. For example, Komen funds allow Siteman to provide free mammograms to more than 3,200 underserved, low-income women in the area.

“Komen’s help is essential in Siteman’s outreach efforts, and without them we simply would not be able to provide screening to the uninsured to the levels they have established,” Kraenzle said.

Research grants are another important part of Race for the Cure. Money raised nationally at the events made possible the more than $12 million in Promise Grants that Komen has awarded Washington University researchers at Siteman Cancer Center since 2011.

Race for the Cure also provides an excellent opportunity to teach high school students about possible careers in health care and about health in general, said Jennifer Irvin, a school-community health educator at BJC School Outreach & Youth Development.

She too organizes a Siteman subteam that has walked for the past 11 years. Members, including Irvin’s husband and children and students she teaches, also volunteer to hand out race T-shirts and to work at Siteman’s education booth. Participating gave one student the knowledge to perform a breast self-exam that detected a lump. It turned out to be benign, but the 18-year-old needed surgery.

“Today it could be someone else, but tomorrow it could be you,” said Irvin, whose oldest daughter will return from college in Atlanta for the St. Louis race. “I think it’s important to make a difference and to strive for a cure.”

As for Tomlin-Watson, she now hosts the holiday dinners her mother once did. The Komen St. Louis Race for the Cure has become a family tradition, too. Members of JoAnn’s Jewels carry fans bearing an image of the smiling matriarch. During the walk, they reminisce about the times they shared with her.

So many families have been affected by breast cancer, a point Tomlin-Watson recognizes every Race for the Cure when she stops at a particular vantage point along the route. From there, she sees the tens of thousands of other people walking, running and remembering alongside her.

“It’s just a humbling sight to see,” she said. “You see all these people coming together for this one cause.”

Those who join the Siteman team for the 5K run or walk will receive two T-shirts – a Komen St. Louis Race for the Cure shirt and a specially designed Siteman team shirt. Registrants who sign up online also are entered into a drawing for one of two Kindle Fire tablets and will receive a one-year subscription to SELF magazine or GQ magazine. The deadline for registering online is midnight May 28. For more information, visit this link.

OT student receives leadership award

2013-05-13 00:00:00

Sanborn

Erin Sanborn, a doctoral student in the Washington University School of Medicine's Program in Occupational Therapy, is the recipient of the 2013 Women in Science Rosalind Kornfeld Leadership Award given by the Academic Women's Network (AWN) at the university.

The leadership award is given each year to women in the graduating class of the school’s MD and/or PhD programs who have demonstrated outstanding leadership in service to, or advancement of, women within the community. The award was named to memorialize Rosalind Kornfeld, PhD, the founding president of AWN and a valued colleague and mentor to many female scientists at the university. She died in 2007.

Sanborn, who this month will receive her doctorate in occupational therapy, is the first occupational therapy student to be given the Rosalind Kornfeld Leadership Award. She also recently was chosen to participate in Clinton Global Initiative University for a proposal related to her occupational therapy doctorate apprenticeship, which involves helping start the first occupational therapy school in Malawi, in sub-Saharan Africa.

To read more about the leadership award and its recipients, visit this link.

Scientists show how nerve wiring self-destructs

Julia Evangelou Strait — 2013-05-09 00:00:00

Elisabetta Babetto, PhD

Mouse nerve axons (green) connect to muscle synapses (red) to coordinate movement. Three days after injury, these axons are protected from degeneration because they are missing Phr1, a gene involved in removing damaged axons from the body. In mice that have the gene, injured green axons fragment and disappear by the third day, leaving the red muscle synapses without nerve connections.

Many medical issues affect nerves, from injuries in car accidents and side effects of chemotherapy to glaucoma and multiple sclerosis. The common theme in these scenarios is destruction of nerve axons, the long wires that transmit signals to other parts of the body, allowing movement, sight and sense of touch, among other vital functions.

Now, researchers at Washington University School of Medicine in St. Louis have found a way the body can remove injured axons, identifying a potential target for new drugs that could prevent the inappropriate loss of axons and maintain nerve function.

“Treating axonal degeneration could potentially help a lot of patients because there are so many diseases and conditions where axons are inappropriately lost,” said Aaron DiAntonio, MD, PhD, professor of developmental biology. “While this would not be a cure for any of them, the hope is that we could slow the progression of a whole range of diseases by keeping axons healthy.”

DiAntonio is senior author of the study that appears online May 9 in the journal Cell Reports.

While axonal degeneration appears to be a major culprit in diseases like multiple sclerosis, it also paradoxically plays an important role in properly wiring the nervous systems of developing embryos.

“When an embryo is building its nervous system, there can be inappropriate or excessive axonal sprouts, or axons that are only needed at one time in development and not later,” DiAntonio said. “These axons degenerate, and that’s very important for wiring the nervous system. And in adult organisms, it might be useful to have a clean and quick way to remove a damaged axon from a healthy nerve, instead of letting it decay and potentially damage its neighboring axons.”

DiAntonio compares the process to programmed cell death, or apoptosis, which is also important in embryonic development. Apoptosis culls unnecessary or damaged cells from the body. If cell death programs become overactive, they can kill healthy cells that should remain. And if apoptosis fails to destroy damaged cells in adults, it can lead to cancer.

The new discovery also underscores the relatively recent understanding that loss of axons is not a passive decay process resulting from injury. Just as apoptosis actively destroys cells, axonal degeneration results from a cellular program that actively removes the damaged axon. In certain diseases, the program may be inappropriately triggered.

“We want to understand axonal degeneration at the same level that we understand programmed cell death, in the hopes of developing drugs to block the process when it becomes overactive,” DiAntonio said.

DiAntonio’s major collaborators in this project include Jeffrey D. Milbrandt, MD, PhD, the James S. McDonnell Professor and head of the Department of Genetics, and first author Elisabetta Babetto, PhD, postdoctoral research scholar.

Studying mice, the researchers found that a gene called Phr1 plays a major role in governing the self-destruction of injured axons. When they removed Phr1 from adult mice, the severed portion of the axons remained intact for much longer than in genetically normal mice.

In the normal mice, a severed axon degenerated entirely after two days. In mice without Phr1, they found that about 75 percent of the severed axons remained at five days, with a quarter persisting at least 10 days after being cut. The mice showed no side effects and suffered no obvious problems due to the missing Phr1.

The findings raise the possibility that blocking the Phr1 protein with a drug could keep damaged axons alive and functional when the body would normally cause the axons to self-destruct.

DiAntonio emphasizes that he is not trying to save axons that have no connection to the rest of the nerve. The paradigm is simply a good way to model nerve injury. In many instances, such as a crush injury or disease processes in which the axon is not severed, blocking the Phr1 protein could potentially preserve an attached axon that would otherwise self-destruct.

Importantly, the research team also looked at optic nerves of the central nervous system, which are damaged in glaucoma, and found similar protective effects from the loss of Phr1.

“This is not the first gene identified whose loss protects mammalian axons from degeneration,” DiAntonio said. “But it is the first one that shows evidence of working in the central nervous system. So it could be important in conditions like glaucoma, multiple sclerosis and other neurodegenerative diseases where the central nervous system is the primary problem.”

DiAntonio also points out possible ways to help cancer patients. Many chemotherapy drugs cause damage to peripheral axons, which may limit the doses a patient can tolerate.

As part of the new study, the researchers showed that intact axons without Phr1 were protected from the damage caused by vincristine, a chemotherapy drug used to treat leukemia, neuroblastoma, Hodgkin’s disease and non-Hodgkin’s lymphoma, among other cancers.

“In this case, the loss of axons is not caused by disease,” DiAntonio said. “It’s caused by the drug doctors are giving. You know the date it will start. You know the date it will stop. This is probably where I am most optimistic that we could make an impact.”

This work was supported by the American-Italian Cancer Foundation, the European Molecular Biology Organization, the Muscular Dystrophy Association and the National Institutes of Health (NIH) grant numbers DA020812, NS065053 and NS078007.

Babetto E, Beirowski B, Russler EV, Milbrandt J, DiAntonio A. The Phr1 ubiquitin ligase promotes injury-induced axon self-destruction. Cell Reports. May 9, 2013.

Obituary: Burton E. Sobel, MD, former director of Cardiovascular Division, 75

Julia Evangelou Strait — 2013-05-10 00:00:00

University of Vermont

Sobel

Burton E. Sobel, MD, internationally known leader in cardiovascular medicine, prolific scientist and former longtime director of the Cardiovascular Division at Washington University School of Medicine in St. Louis, died Friday, May 3, 2013, at his home in Vermont, after a long illness. He was 75.

Sobel served as chief of cardiology at Washington University and at Barnes Hospital from 1974 until 1994. He then moved to the University of Vermont, where he was a University Distinguished Professor of Medicine and a professor of biochemistry as well as founder and first director of the Cardiovascular Research Institute at the University of Vermont.

Sobel’s research was far-reaching and included major contributions to the treatment of heart attacks, including best methods for dissolving blood clots, and the understanding of cardiovascular disease in the context of Type 2 diabetes and insulin resistance.

He pioneered the development of tissue plasminogen activators (tPA), among the most commonly used clot-busting drugs. Sobel’s early work in this area laid the foundation for his leadership roles in multicenter clinical trials that showed the effectiveness of drugs, including tPA, heparin and aspirin, in dissolving clots and reducing deaths due to heart attacks and coronary artery disease.

More recently, Sobel was a leader in the evolving understanding of the relationship between diabetes and heart disease.

“Dr. Sobel was the consummate physician scientist who translated basic science concepts regarding clot-dissolving agents into clinical trials that have saved the lives of countless patients,” said Douglas L. Mann, MD, the Tobias and Hortense Lewin Professor of Medicine and current chief of the Cardiovascular Division. “He also was responsible for putting Washington University’s Cardiovascular Division on the map. His academic legacy lives on here through the innumerable residents, fellows and faculty that he trained and supported.”

Sobel earned his medical degree from Harvard Medical School in 1962. After an internship and residency at Peter Bent Brigham Hospital in Boston, he continued his cardiology training at the National Institutes of Health in Bethesda, Md. During this period, he also served in the U.S. Public Health Service. In 1968, he joined the faculty of University of California, San Diego.

He came to Washington University in 1973 as an associate professor of medicine and director of the Cardiovascular Division at the School of Medicine and at Barnes and Wohl Hospitals. He was named the Tobias and Hortense Lewin Distinguished Professor in Cardiovascular Disease in 1985. After his tenure in St. Louis, Sobel joined the faculty of the University of Vermont as chair of the Department of Medicine in 1994.

A prolific academic, Sobel published more than 900 peer-reviewed articles, invited reviews, editorials and book chapters. He also held positions on the editorial boards of many high-profile medical journals focused on cardiology, including editor of Circulation, associate editor of The Journal of Clinical Investigation, and board member of Annals of Internal Medicine and The American Journal of Cardiology. As editor of Circulation, he is credited with innovations that raised the journal’s profile and shaped the field of cardiology and its current directions.

He received numerous honors and awards over his long career, including the Eugene H. Drake Memorial Award from the American Heart Association and a Distinguished Scientist Award from the American College of Cardiology. In 2010, he received the Distinguished Scientist Award from the Society of Experimental Biology and Medicine. The same organization also continues to honor him with the named Burton E. Sobel Annual Young Investigator Award.

Sobel was a fellow of the American Association for the Advancement of Science, the American College of Cardiology, the American College of Physicians, and The Royal Society of Medicine, UK, among others.

Sobel is survived by his wife of 55 years, Susan; his children, Jonathan and Elizabeth; and a granddaughter.

A funeral service was held May 8 in South Burlington, Vt.

Siteman director appointed vice chair of national cancer network

Jim Goodwin — 2013-05-08 00:00:00

Eberlein

Timothy Eberlein, MD, director of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, has been named vice chair of the National Comprehensive Cancer Network (NCCN) board of directors.

The network, which comprises 23 of the world’s leading cancer centers, develops and updates guidelines for treating breast, lung, prostate and other types of cancer.

“It is a tremendous honor to be named to the board of such an outstanding medical association,” Eberlein said. “I look forward to working with my fellow board members to promote exceptional care for patients and sound public policy.”

Siteman is Missouri’s only member of the NCCN, formed in 1995 to improve the quality, effectiveness and efficiency of cancer care.

“We are very pleased that Dr. Eberlein has been elected as vice chair of the NCCN board of directors,” said Robert W. Carlson, MD, chief executive officer of the association. “His perspectives as a cancer center director, scientist, physician and administrator will be invaluable to NCCN.”

Eberlein has been director of Siteman since its inception in 1998. He also serves as the Bixby Professor and Spencer T. and Ann W. Olin Distinguished Professor and chairman of the Department of Surgery at the School of Medicine, as well as surgeon-in-chief at Barnes-Jewish.

For more information about the NCCN, visit www.nccn.org.

The Siteman Cancer Center, the only NCI-designated Comprehensive Cancer Center in Missouri, is ranked a top 10 cancer facility by U.S. News & World Report. Comprising the cancer research, prevention and treatment programs of Barnes-Jewish Hospital and Washington University School of Medicine, Siteman is also Missouri’s only member of the National Comprehensive Cancer Network.

Moley elected president of gynecologic society

Diane Duke Williams — 2013-05-08 00:00:00

Kelle Moley, MD, the James P. Crane Professor of Obstetrics and Gynecology at Washington University School of Medicine in St. Louis, has been elected president of the Society of Gynecologic Investigation (SGI).

Moley

The SGI is an international society that aims to inspire investigation of global problems in women’s reproductive health through achievements in discovery, transferring new knowledge and training future scholars.

Moley, also a professor of cell biology and physiology, additionally is vice chair and director of basic science research in the Department of Obstetrics and Gynecology and a physician at Barnes-Jewish Hospital.

She is one of a handful of people in the world studying how maternal obesity as well as type 1 and type 2 diabetes affect the implantation and development of mouse embryos, which could provide insight into the pregnancy outcomes of these diseases in humans.

Her work has established that short-term exposure to high concentrations of glucose or insulin during the first 72 hours after fertilization can alter development and result in an increase of congenital malformations, miscarriages and long- term effects on the offspring.

Moley also is co-director of the Institute of Clinical and Translational Science, director of the fellowship program in reproductive endocrinology and program director of the Women’s Reproductive Health Research Career Development Program.

Obituary: William H. Daughaday, former director of metabolism, 95

Jim Dryden — 2013-05-10 00:00:00

Daughaday

William H. Daughaday, MD, a leading diabetes researcher, world authority on growth hormone and the former director of the metabolism division at Washington University School of Medicine in St. Louis, died Friday, May 3, 2013, after a long illness, in Milwaukee. He was 95.

In an article about the early years of the metabolism division, he wrote that the division was characterized by “brown-bag lunches with free exchange of scientific information and lively discussion of the world and cultural affairs” where “yelling to one another from the various laboratories” was standard practice.

His interest in endocrinology dated back to his high school days in Chicago. The father of one of his closest friends was the head of endocrinology at Northwestern University Medical School. Daughaday visited the laboratory regularly and worked there after his first year at Harvard Medical School.

Daughaday was at Washington University from 1947 until 1994.

“Bill Daughaday was a brilliant physician scientist and a gifted clinician and teacher who became fascinated with endocrinology very early in his career and rapidly became one of the preeminent academic endocrinologists of his time,” said Victoria J. Fraser, MD, the Adolphus Busch Professor and head of the Department of Medicine. “His scientific contributions transformed the field, and he made a huge impact here at Washington University through his research, patient care and the educational programs he developed. Bill will always be remembered for his scientific curiosity, intellect and leadership.”

A highly respected clinician and teacher, Daughaday trained several generations of respected endocrinologists. In 1972, with the help of the late Louis V. Avioli, MD, Daughaday authored the first board certification examination for endocrinology and metabolism.

He was the founding director of Washington University’s Diabetes and Endocrinology Research Center in 1975 and that center’s successor, the Diabetes Research and Training Center, in 1978. The latter has been continuously funded for 36 years. In 1983, Daughaday was named the first Irene E. and Michael M. Karl Professor of Endocrinology and Metabolism.

Among his scientific contributions was his discovery of insulin-like growth factors, which are proteins that help neurons survive, interact with skeletal muscle tissue and protect cartilage.

Daughaday also did pioneering work developing and applying tests to detect the presence of growth hormone, proposing that growth hormone acted on the liver to stimulate the release of insulin-like growth factor 1. He also discovered how tumors that secrete abnormally high levels of insulin-like growth factor 2 can cause profoundly low blood sugar.

He came to the School of Medicine as an assistant resident in medicine at Barnes Hospital. Shortly after that, he did a research fellowship with Gerty and Carl Cori, a laboratory that helped produce eight Nobel Laureates. He joined the faculty and became the first director of the metabolism division (now the Division of Endocrinology, Metabolism and Lipid Research) in 1951, rising to the rank of professor of medicine in 1963.

Daughaday was a Phi Beta Kappa graduate of Harvard College in 1940 and an Alpha Omega Alpha graduate of Harvard Medical School in 1943. After earning his medical degree, he completed an internship and research fellowship at Boston City Hospital. Then he spent 20 months in the U.S. Army, serving as a medical officer near the end of World War II in Italy.

He published more than 300 scientific articles, and his work earned him many honors, including the Fred Conrad Koch Award of the Endocrine Society (a group for which he served as president), election to the American Society for Clinical Investigation and to the Association of American Physicians and the National Academy of Sciences. He also received Washington University School of Medicine’s Second Century Award in 1993.

Daughaday sat on the NIH advisory council to the National Institute of Diabetes and Digestive and Kidney Diseases. He chaired the American Board of Internal Medicine’s subspecialty panel on endocrinology and metabolism, and he served as editor of the Journal of Laboratory and Clinical Medicine and the Journal of Clinical Endocrinology and Metabolism, as well as associate editor of the Journal of Clinical Investigation and as a member of several other editorial boards.

Following his retirement from Washington University in 1994, Daughaday joined the faculty at the University of California, Irvine, as a clinical professor of medicine and moved to Balboa Island, Calif.

He is survived by two children, Elizabeth Daughaday Axelrod and John Daughaday; four grandchildren and three great grandchildren. His first wife, Hazel Judkins Daughaday, died in 1991. His second wife, Nancy Wolcott Ebsen, died in 2008.

A private graveside service is planned for May 25 in St. Louis.

Memorial contributions may be made to the Division of Endocrinology, Metabolism and Lipid Research in the Department of Medicine at Washington University School of Medicine. They may be sent to the attention of Helen Z. Liu, 7425 Forsyth Blvd. Ste. 2100, St. Louis, Mo. 63105. Memorial gifts also may be given online via this link.

Nerve stimulation for severe depression changes brain function

Jim Dryden — 2013-05-07 00:00:00

PET scans of patients successfully treated with vagus nerve stimulation show marked increases in cerebral glucose metabolism after 12 months of treatment (bottom image, red/orange area in yellow circle) in parts of the brainstem thought to be critical in depression. In nonresponders, glucose metabolism decreased in the same brain region (top image, blue/green area in yellow circle).

For nearly a decade, doctors have used implanted electronic stimulators to treat severe depression in people who don’t respond to standard antidepressant therapy.

Now, preliminary brain scan studies conducted by researchers at Washington University School of Medicine in St. Louis are beginning to reveal the processes occurring in the brain during stimulation and may provide some clues about how the device improves depression. They found that vagus nerve stimulation brings about changes in brain metabolism weeks or even months before patients begin to feel better.

The findings will appear in an upcoming issue of the journal Brain Stimulation and are now available online.

“Previous studies involving large numbers of people have demonstrated that many with treatment-resistant depression improve with vagus nerve stimulation,” said first author Charles R. Conway, MD, associate professor of psychiatry. “But little is known about how this stimulation works to relieve depression. We focused on specific brain regions known to be connected to depression.”

Conway’s team followed 13 people with treatment-resistant depression. Their symptoms had not improved after many months of treatment with as many as five different antidepressant medications. Most had been depressed for at least two years, but some patients had been clinically depressed for more than 20 years.

All of the participants had surgery to insert a device to electronically stimulate the left vagus nerve, which runs down the side of the body from the brainstem to the abdomen. Once activated, the device delivers a 30-second electronic stimulus to the vagus nerve every five minutes.

To establish the nature of the treatment’s effects on brain activity, the researchers performed positron emission tomography (PET) brain imaging before the initiation of stimulation, and again three and 12 months after stimulation had begun.

Eventually, nine of the 13 subjects experienced improvements in depression with the treatment. However, in most cases it took several months for improvement to occur.

Remarkably, in those who responded, the scans showed significant changes in brain metabolism following three months of stimulation, which typically preceded improvements in symptoms of depression by several months.

“We saw very large changes in brain metabolism occurring far in advance of any improvement in mood,” Conway said. “It’s almost as if there’s an adaptive process that occurs. First, the brain begins to function differently. Then, the patient’s mood begins to improve.”

Conway

Although the patients remained on antidepressants for several months after their stimulators were implanted, Conway says many of those who responded to the device eventually were able to stop taking medication.

“Sometimes the antidepressant drugs work in concert with the stimulator, but it appears to us that when people get better, it is the vagus nerve stimulator that is doing the heavy lifting,” Conway explained. “Stimulation seems to be responsible for most of the improvement we see."

Additionally, the PET scans demonstrated that structures deeper in the brain also begin to change several months after nerve stimulation begins. Many of those structures have high concentrations of brain cells that release dopamine, a neurotransmitter that helps control the brain’s reward and pleasure centers and also helps regulate emotional responses.

There is a consensus forming among depression researchers that problems in dopamine pathways may be particularly important in treatment-resistant depression, according to Conway. And he said the finding that vagus nerve stimulators influence those pathways may explain why the therapy can help and why, when it works, its effects are not transient. Patients who respond to vagus nerve stimulation tend to get better and stay better.

“We hypothesized that something significant had to be occurring in the brain, and our research seems to back that up,” he said.

Funding for this research comes from the National Institute of Mental Health (NIMH) and the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH). Other funding was provided by a Young Investigator Award to Charles Conway from the National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) and the Sidney R. Baer Jr. Foundation. Cyberonics, the maker of the vagus nerve stimulation device, donated three cost-free devices to subjects in this trial.
NIH grant numbers are 1K08MH078156-01A1, 9K24MH07951006 and P30NS048056.

Conway CR, Chibnall JT, Gebara MA, Price JL, Snyder AZ, Mintun MA, Craig, AD, Cornell ME, Perantie DC, Giuffra LA, Bucholz RD, Sheline YI. Association of cerebral metabolic activity changes with vagus nerve stimulation antidepressant response in treatment-resistant depression. Brain Stimulation, published online Feb. 2013: doi: 10.1016/j.brs.2012.11.006

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Three faculty elected to National Academy of Sciences

2013-05-06 00:00:00

Three Washington University in St. Louis scientists are among the 84 members and 21 foreign associates elected to the National Academy of Sciences this year. Election to the academy is considered one of the highest honors that can be accorded a U.S. scientist or engineer.

The university's new academy members are:

Stephen M. Beverley, PhD, the Marvin A. Brennecke Professor of Molecular Microbiology and chair of the Department of Molecular Microbiology in the School of Medicine;
Robert D. Schreiber, PhD, Alumni Endowed Professor of Pathology and Immunology and professor of molecular microbiology in the School of Medicine and co-leader of the Tumor Immunology Program at Siteman Cancer Center;
Joan E. Strassmann, PhD, professor of biology in Arts & Sciences.

“I’m still in shock,” said Beverley. “I got the news a few minutes before boarding a flight from London back to St. Louis, and I didn’t really need the plane.”

Beverley
Beverley studies the biology of the protozoan parasite Leishmania, including virulence factors, host response and basic metabolic functions of the parasite.

Leishmania infection, known as leishmaniasis, affects an estimated 12 million people worldwide. It is mainly spread by sand fly bites and is a major public health problem in the Mediterranean basin, Asia, Africa, the Middle East, and Central and South America. Symptoms include large skin lesions, fever, swelling of the spleen and liver, and, in more serious forms of the disease, disfigurement and death.

Beverley and his colleagues have probed many aspects of Leishmania biology through the development and application of advanced genetic tools.

Accomplishments in recent years have included the discovery that one group of Leishmania parasites uses a genetic regulatory system called RNA interference. This system normally is used to control mobile genetic elements that can disrupt the parasite's chromosomes. But scientists can now use the same system to turn genes on and off in the parasite, helping to identify which genes are most important for the infectious process.

Beverley is also active in the hunt for new drug treatments and vaccines for Leishmania.

Beverley earned a PhD in biochemistry from the University of California, Berkeley, and did postdoctoral research at Stanford University. In 1983, he moved to Harvard Medical School, where he eventually became the Hsien and Daisy Yen Wu Professor and interim chair of the Department of Biological Chemistry & Molecular Pharmacology. In 1997, he joined the faculty at Washington University School of Medicine as head of the Department of Molecular Microbiology.

Schreiber

Schreiber studies the intricate relationship between cancer and the immune system. With his colleagues, he has revived a century-old model of how the immune system interacts with tumors.

When Schreiber began his research, the accepted model of this relationship, called cancer immunosurveillance, suggested that if the immune system recognized a tumor, it would attack the tumor with the same weapons it uses to eliminate invading microorganisms, not stopping until the tumor was destroyed or the immune system’s resources were exhausted.

The model revived by Schreiber and his colleagues, known as cancer immunoediting, also asserts that the immune system can attack tumors. But they propose that three very different outcomes can result. The immune system can eliminate cancer, destroying it; the immune system can establish equilibrium with cancer, checking its growth but not eradicating it; or the cancer can escape from the immune system, likely becoming more malignant in the process.

The research has had far-reaching effects on clinical efforts to enlist the immune system’s help in the battle against cancer. Schreiber’s insight that the immune system can drive cancers into dormancy, for example, has suggested that immune therapy may one day allow cancer to become a chronic but controllable condition.

Schreiber and his colleagues recently demonstrated that some mutated genes in tumors can give rise to tumor-specific protein antigens. They showed that these antigens can be identified using next generation genomic sequencing and bioinformatic techniques, and their efforts now are focused on refining this approach to develop safe and effective personalized cancer immunotherapies.

Schreiber earned a doctorate from the State University of New York at Buffalo in 1973. After a stretch as a postdoctoral fellow and faculty member at the Research Institute of the Scripps Clinic in La Jolla, Calif., he was recruited to Washington University in 1985. He received a Washington University Faculty Achievement Award in 2008.

Strassmann’s work focuses on cooperative alliances that have occurred at several important steps in the evolution of life that have proven evolutionarily and ecologically successful.

Strassmann

In collaboration with her husband and colleague, David C. Queller, PhD, the Spencer T. Olin Professor of Biology in Arts & Sciences, she has measured genetic relatedness within colonies of many wasp species, including Polistes exclamans, and showed that kin selection theory predicts the existence and outcome of within-family conflicts of interest. They also have pioneered the use of DNA microsatellites for relatedness estimation.

In 1998, they began working with the social amoebae Dictyostelium discoideum, a model organism for exploring the evolution of social interactions at the physiological, genetic and genomic levels. In a series of papers, they have demonstrated the power of social evolution theory in explaining multicellular organization, from developmental pathways to cell adhesion.

She earned a PhD in 1979 from the University of Texas at Austin. From 1980 to 2011, Strassmann was on the faculty of Rice University in Houston, Texas, where she was the Harry C. and Olga K. Wiess Professor in the Department of Ecology and Evolutionary Biology. In 2011, she became a professor of biology at Washington University. That same year, she was elected president of the Animal Behavior Society.

New perspective needed for role of major Alzheimer's gene

Michael C. Purdy — 2013-05-06 00:00:00

Scientists’ picture of how a gene strongly linked to Alzheimer’s disease harms the brain may have to be revised, researchers at Washington University School of Medicine in St. Louis have found.

Holtzman

People with harmful forms of the APOE gene have up to 12 times the risk of developing Alzheimer’s disease compared with those who have other variations of the gene.

Many researchers believe that the memory loss and cognitive problems of Alzheimer’s result from the buildup over many years of brain amyloid plaques. The plaques are made mostly of a sticky substance called amyloid beta.

For years, researchers have thought that the APOE gene increases Alzheimer’s risk by producing a protein that binds to amyloid beta. Scientists thought that this bond could make it easier for plaques to form.

But in a new study now available online in the Proceedings of the National Academy of Sciences, Washington University researchers show that APOE and amyloid beta don’t bind together in cerebrospinal fluid and in fluids present outside cells grown in dishes. This means they are unlikely to bind together in the fluids circulating in the brain. The cerebrospinal fluid was taken from people who were cognitively normal but have forms of APOE that increase the risk of Alzheimer’s.

“This is the first time we’ve looked at naturally produced APOE and amyloid beta to see if and how much they bind together, and we found that they have very little interaction in the fluids bathing the brain,” said David M. Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of neurology. “This suggests that we may need to rethink any therapeutic strategies that target APOE to slow amyloid plaque accumulation and Alzheimer’s.”

According to Holtzman, leading Alzheimer’s researchers recently agreed that targeting APOE is a promising approach both to gain a better understanding of and to improve treatments for Alzheimer’s. But to do that, scientists first must fully understand how the harmful forms of APOE increase risk of the disease.

Verghese

“APOE is a major player in Alzheimer’s, there’s no question about that,” said Philip Verghese, PhD, a postdoctoral research associate. “We did some additional studies in mice and cell cultures that suggested the APOE protein may be blocking a pathway that normally helps degrade amyloid beta.”

APOE is involved in the metabolism of fats, cholesterol and vitamins throughout the body. Scientists have identified three different forms of the gene that each make a slightly different version of the protein.

One version, APOE 2, produces a protein that significantly reduces Alzheimer’s risk. Another, APOE 4, increases risk. Each person has two copies of the gene, and if both copies are APOE 4, the chance of developing Alzheimer’s rises dramatically.

“About 60 percent of the patients we see in the Alzheimer’s clinics have at least one copy of APOE 4,” Holtzman said. “In contrast, only about 25 percent of cognitively normal 70-year-olds have a copy of APOE 4.”

Verghese tested cerebrospinal fluid samples from people who had either two copies of APOE 4 or two copies of APOE 3, another form of the gene that is not associated with increased Alzheimer’s risk.

“We also found that APOE 2, the protective form of the protein, doesn’t bind to amyloid beta in body fluids,” Verghese said.

In follow-up studies, Verghese showed that APOE and amyloid beta “compete” to bind to a receptor on support cells in the brain known as astrocytes.

“Studies by other researchers have shown that astrocytes can degrade amyloid beta,” Verghese said. “The receptor we identified may be important for getting amyloid beta into the astrocyte so it can be broken down. It’s possible that when the harmful forms of APOE bind to the receptor, this reduces the opportunities for amyloid to be degraded.”

The researchers are planning follow-up studies of the effects of APOE-blocking treatments in mice.

This work was supported by the American Health Assistance Foundation and the National Institutes of Health (Grants AG034004 , AG13956, NS074969, and AG027924).

Verghese PB, Castellano JM, Garai K, Wang Y, Jiang H, Shah A, Bu G, Frieden C, Holtzman DM. ApoE influences amyloid beta clearance despite minimal apoE/amyloid-beta association in physiological conditions. Proceedings of the National Academy of Sciences, published online.

Discovery helps show how breast cancer spreads

Julia Evangelou Strait — 2013-05-05 00:00:00

Nature Cell Biology

Collagen fiber alignment at the tumor boundary (dashed lines) is predictive of prognosis. Fibers that tend to be perpendicular to the tumor surface (top right, for example) encourage metastasis and indicate a poor prognosis. Fibers that run parallel to the tumor surface (bottom right) protect against cancer spreading. Tumors without DDR2 or SNAIL1 tend to show the protective parallel fiber alignment.

Researchers at Washington University School of Medicine in St. Louis have discovered why breast cancer patients with dense breasts are more likely than others to develop aggressive tumors that spread. The finding opens the door to drug treatments that prevent metastasis.

It has long been known that women with denser breasts are at higher risk for breast cancer. This greater density is caused by an excess of a structural protein called collagen.

“We have shown how increased collagen in the breasts could increase the chances of breast tumors spreading and becoming more invasive,” said Gregory D. Longmore, MD, professor of medicine. “It doesn’t explain why women with dense breasts get cancer in the first place. But once they do, the pathway that we describe is relevant in causing their cancers to be more aggressive and more likely to spread.”

The results appeared online May 5 in Nature Cell Biology.

Working in mouse models of breast cancer and breast tumor samples from patients, Longmore and his colleagues showed that a protein that sits on the surface of tumor cells, called DDR2, binds to collagen and activates a multistep pathway that encourages tumor cells to spread.

“We had no idea DDR2 would do this,” said Longmore, also a professor of cell biology and physiology. “The functions of DDR2 are not well understood, and it has not been implicated in cancer — and certainly not in breast cancer — until now.

At the opposite end of the chain of events initiated by DDR2 is a protein called SNAIL1, which has long been associated with breast cancer metastasis. Longmore and his colleagues found that DDR2 is one factor helping to maintain high levels of SNAIL1 inside a tumor cell’s nucleus, a necessary state for a tumor cell to spread. Although they found it is not the only protein keeping SNAIL1 levels high, Longmore said DDR2 is perhaps the one with the most potential to be inhibited with drugs.

“It’s expressed only at the edge of the tumor,” said Longmore, a physician at Siteman Cancer Center at Washington University and Barnes-Jewish Hospital and co-director of the Section of Molecular Oncology. “And it’s on the surface of the cells, which makes it very nice for developing drugs because it’s so much easier to target the outside of cells.”

Longmore emphasized that DDR2 does not initiate the high levels of SNAIL1. But it is required to keep them elevated. This mechanism that keeps tumor cells in a state that encourages metastasis requires constant signaling – meaning constant binding of DDR2 to collagen.

If that continuous signal is blocked, the cell remains cancerous, but it is no longer invasive. So a drug that blocks DDR2 from binding with collagen won’t destroy the tumor, but it could inhibit the invasion of these tumors into surrounding tissue and reduce metastasis.

One possible way DDR2 may govern metastasis is its influence on the alignment of collagen fibers. If fibers are aligned parallel to the tumor’s surface, the tumor is less likely to spread. But fibers aligned perpendicular to the surface of the tumor provide a path for the tumor cells to follow and encourage spreading. Tumors without DDR2 or SNAIL1 tend to show the parallel fiber alignment that is protective against spreading.

“This whole notion of fiber alignment and the tumor interface is a hot topic right now,” Longmore said. “Our co-authors at the University of Wisconsin have developed a scoring method for collagen alignment that correlates with prognosis. And the bad prognosis disappears when you take away DDR2.”

With the current emphasis on genetic mutations in cancer, Longmore is careful to point out that 70 percent of invasive ductal breast cancers show DDR2. But in 95 percent of these tumors, the genes in this pathway – from DDR2 to SNAIL1 – are entirely normal, without mutations.

“If you did genomic sequencing, all of these particular genes would be normal,” Longmore said. “You have to be careful not to just focus on mutations in cancer. This is an example of normal genes put together in an aberrant situation. The change in the environment — the tumor and its surroundings — causes the abnormal expression of these proteins. It is abnormal, but it’s not caused by a gene mutation.”

In early drug development efforts, Longmore and his colleagues have done some preliminary work looking for small molecules that may inhibit DDR2 binding to collagen.

“Currently there are no DDR2-specific inhibitors,” Longmore said. “But there is great interest and work being done here and elsewhere to develop them.”

This work was funded by the National Institutes of Health (NIH) grants P50CA94056 to the Imaging Core of the Siteman Cancer Center at Washington University and Barnes-Jewish Hospital, GM080673, CA143868 and F31CA165729, and by Susan G. Komen for the Cure.

Zhang K, Corsa CA, Ponik SM, Prior JL, Piwnica-Worms D, Eliceiri KW, Keely PJ, Longmore GD. The collagen receptor discoidin domain receptor 2 stabilizes SNAIL1 to facilitate breast cancer metastasis. Nature Cell Biology. Online May 5, 2013.

Elson elected fellow of arts and sciences academy

Julia Evangelou Strait — 2013-05-03 00:00:00

Washington University School of Medicine in St. Louis faculty member Elliot L. Elson, PhD, has been elected a fellow of the American Academy of Arts and Sciences.

Elson, the Alumni Endowed Professor of Biochemistry and Molecular Biophysics, is one of 186 Americans elected as fellows this year by the academy, an organization formed in 1780 to cultivate the arts and sciences and to recognize leadership in scholarship, business, the arts and public affairs.

The academy has more than 4,500 members, including some 250 Nobel laureates and 60 Pulitzer Prize winners. Fellows are selected through a competitive process that recognizes individuals who have made prominent contributions to their disciplines and society.

“I am delighted that a member of our outstanding faculty has received this tremendous honor,” said Chancellor Mark S. Wrighton. “Dr. Elson is a dedicated scientist, and this recognition is well-deserved. This achievement demonstrates the good fortune we have had at Washington University in attracting premier faculty.”

This year’s new fellows and foreign honorary members will be welcomed during an induction ceremony Oct. 12 at the academy’s headquarters in Cambridge, Mass.

Elson

Elson joined the faculty of Washington University as a professor in 1979. In addition to his appointment in the Department of Biochemistry and Molecular Biophysics, he is also a professor of biomedical engineering in the School of Engineering & Applied Science and an adjunct professor of physics in Arts & Sciences.

His research focuses on cellular motion, the movement and distribution of cell surface proteins and the forces that determine the shapes of cells. He and members of his lab also have studied artificial cardiovascular tissues, including their mechanical and electrical properties.

Elson and his lab members also are well-known for designing and building their own unique instruments to answer specialized questions. One such instrument evolved from a novel technique to measure molecular motion. Elson began developing the technique in the late 1960s, while a faculty member at Cornell University. Called fluorescence correlation spectroscopy (FCS), it has evolved into a sophisticated technology that has been widely adopted in labs around the world.

Elson, a St. Louis native, earned a doctoral degree in biochemistry from Stanford University in 1964 and went on to postdoctoral training at the University of California, San Diego. He joined the faculty of Cornell University in 1968.

In 2007, Elson received the Gregorio Weber Award for Excellence in Fluorescence Theory and Applications. The international award recognizes distinguished individuals who have made original and significant contributions to the field of fluorescence. Elson was honored with the Weber Award for his extensive research in fluorescence, including the development of FCS and his continuing work to refine and advance the technique.

Elson has authored more than 160 articles in peer-reviewed scientific journals. He has served on the editorial boards of several of these journals, including The Journal of Cell Biology, Biopolymers and Biophysical Journal. He is a member of the Biophysical Society and the American Association for the Advancement of Science.

School of Medicine, SLCH and BJH nurses honored with 2013 Excellence in Nursing awards

2013-05-03 00:00:00

Shown are Washington University School of Medicine nurses who were winners or finalists in the 2013 Excellence in Nursing awards from St. Louis Magazine. In the top row from the left are: Jamie Menendez, Vicky Peck, Linda Black, Stacy Pokorny, Barb Miller, and Reida McDowell. Seated, from the left, are: Cassandra Ward, Bernadette Hinrichs, Robyn Myers and Mandy Drozda.

Several Washington University School of Medicine, Barnes-Jewish Hospital (BJH) and St. Louis Children’s Hospital (SLCH) nurses received the 2013 Excellence in Nursing Award from St. Louis Magazine. The award honors nurses who have made a difference in the lives of their patients and colleagues.

The fourth annual awards were announced April 25. The winners included:

• Mary Megehan, a cardiac-intensive care staff nurse at SLCH, award recipient in the intensive care category;

• Karen Balakas, a nurse researcher at SLCH, recipient in the research category;

• Linda Black, a staff nurse in the School of Medicine Department of Surgery’s urologic surgery division, recipient in the acute care/general medicine category;

• Benita Austin, a nurse practitioner in palliative-care service at BJH, recipient in hospice/home health/palliative care;

• Meranda Scherer, a resource nurse in transplant and hepatobiliary surgery at BJH, recipient in the medical-surgical nursing category;

• Diana Kraus, a nurse who helps coordinate trauma care at SLCH, recipient in the management/nurse executive/nurse leader category;

• Cassandra Ward, a nurse in the Memory Diagnostic Center in the School of Medicine’s Department of Neurology, recipient in the neurology/psychology/behavioral health category;

• Barbara Logue, a staff nurse in the cardiothoracic intensive care unit at BJH, recipient in the cardiovascular category.

Several School of Medicine, BJH and SLCH nurses were finalists in the program. They are:

• Julie Spencer, Goldfarb School of Nursing at Barnes-Jewish College;

• Margaret Emmert Capriglione, BJH;

• Rinnah MacVittie, BJH;

• Lisa Murphy, BJH;

• Stacy Pokorny, School of Medicine, SLCH;

• Bernadette Henrichs, School of Medicine, Goldfarb School of Nursing at Barnes-Jewish College;

• Barbara Miller, School of Medicine, SLCH;

• Colleen Becker, BJH;

• Marianne Fournie, Barnes-Jewish West County Hospital;

• Victoria Peck, School of Medicine;

• Robyn Myers, School of Medicine;

• Reida McDowell, School of Medicine, Siteman Cancer Center;

• Jamie Menendez, School of Medicine;

• Donna Kaempfe, SLCH;

• Mandy Drozda, School of Medicine, SLCH;

• Tammy Heffner, SLCH;

• Margaret Ann Shaner, SLCH;

• Julie Stumpf, SLCH.

School of Medicine commencement speakers

2013-05-03 00:00:00

Washington University commencement exercises for all schools will be at 8:30 a.m. May 17 in the Quadrangle of the Danforth Campus.

Additionally, the School of Medicine’s Recognition Ceremony will be at 3 p.m. in the Ferrara Theater of America’s Center, 701 Convention Plaza. The School of Medicine's commencement speaker will be Sandeep Jauhar, MD, PhD, cardiologist and director of the Heart Failure Program at Long Island Jewish Medical Center and author of “Intern: A Doctor’s Initiation.”

The school's student speaker will be Ignacio Becerra-Licha, class president, candidate for a doctor of medicine.

The speaker for the Program in Audiology and Communication Sciences will be Richard A. Chole, MD, PhD, Lindburg Professor and head of the Department of Otolaryngology, at 1 p.m. in the Farrell Learning and Teaching Center, Connor Auditorium.

The speaker for the Program in Physical Therapy will be Edelle Field-Fote, PhD, vice chair and graduate program director for the Department of Physical Therapy, University of Miami Miller School of Medicine, at 1:30 p.m. in the Khorassan Ballroom, The Chase Park Plaza, 212 N. Kingshighway. The event's faculty speaker will be Shirley Sahrmann, PhD, professor of physical therapy, of cell biology and physiology, and of neurology. The student speaker will be Daniel Braughton, candidate for a doctorate in physical therapy.

The speaker for the Program in Occupational Therapy will be David Newburger of Newburger & Vossmeyer in St. Louis, co-director of the Starkloff Disability Institute and commissioner of the City of St. Louis Office on the Disabled, at 1 p.m. in Graham Chapel. The event's faculty speaker will be Kerri Morgan, instructor of occupational therapy and neurology. Student speakers will be Elizabeth Williams, candidate for a master’s in occupational therapy, and Erin Sanborn, candidate for a doctorate in occupational therapy.

Speakers for the Program in Clinical Investigation and the Program in Population Health Sciences will be Larry Shapiro, MD, executive vice chancellor for medical affairs and dean of the School of Medicine; Victoria J. Fraser, MD, the Adolphus Busch Professor and head of the Department of Medicine; and Graham Colditz, MD, DrPh, deputy director of the Institute for Public Health, the Niess-Gain Professor of Surgery and professor of medicine. The ceremony will begin at 4 p.m. Thursday, May 16, in the King Center in the Bernard Becker Medical Library.

For more information on School of Medicine commencement activities, follow this link.

Author of book about the famed Cori Laboratory to open Cori Lecture May 8

2013-05-03 00:00:00

John Exton, MD, PhD, the author of Crucible of Science — a book detailing the history of a unique laboratory at Washington University and of Carl and Gerty Cori, the tremendous biochemists who established it — will make opening remarks at the Carl and Gerty Cori Lecture May 8.

Exton is a professor of molecular physiology and biophysics at the Vanderbilt University School of Medicine and an investigator of the Howard Hughes Medical Institute.

His book tells the history of the Coris, winners of the Nobel Prize in 1947, and of the laboratory, which has produced some of the top scientists in the U.S., including six other Nobel Prize winners: Severo Ochoa and Arthur Kornberg in 1959; Luis Leloir in 1970; Earl Sutherland in 1971; Christian de Duve in 1974; and Edwin Krebs in 1992.

Exton will speak at 3:30 p.m. in the Eric P. Newman Education Center first-floor auditorium on the Medical Campus.

The Cori Lecture will follow at 4 p.m. with speaker James A. Spudich, the Douglass M. and Nola Leishman Professor of Biochemistry and of Cardiovascular Disease at Stanford University. Spudich’s talk is titled “The Underlying Molecular Basis of Human Hypertrophic and Dilated Cardiomyopathies.”

The event is free and open to the public.

Unusual comparison nets new sleep loss marker

Michael C. Purdy — 2013-05-02 00:00:00

For years, Paul Shaw, PhD, a researcher at Washington University School of Medicine in St. Louis, has used what he learns in fruit flies to look for markers of sleep loss in humans.

Shaw

Shaw reverses the process in a new paper, taking what he finds in humans back to the flies and gaining new insight into humans as a result: identification of a human gene that is more active after sleep deprivation.

“I’m calling the approach cross-translational research,” said Shaw, associate professor of neurobiology. “Normally we go from model to human, but there’s no reason why we can’t take our studies from human to model and back again.”

Shaw and his colleagues plan to use the information they are gaining to create a panel of tests for sleep loss. The tests may one day help assess a person’s risk of falling asleep at the wheel of a car or in other dangerous contexts.

PLOS One published the results April 24.

Scientists have known for years that sleep disorders and disruption raise blood serum levels of interleukin 6, an inflammatory immune compound. Shaw showed that this change is also detectable in saliva samples from sleep-deprived rats and humans.

Based on this link, Shaw tested the activity of other immune proteins in humans to see if any changed after sleep loss. The scientists took saliva samples from research participants after they had a normal night’s sleep and after they stayed awake for 30 hours. They found two immune genes whose activity levels rose during sleep deprivation.

“Normally we would do additional human experiments to verify these links,” Shaw said. “But those studies can be quite expensive, so we thought we’d test the connections in flies first.”

The researchers identified genes in the fruit fly that were equivalent to the human genes, but their activity didn’t increase when flies lost sleep. When they screened other, similar fruit fly genes, though, the scientists found one that did.

“We’ve seen this kind of switch happen before as we compared families of fly genes and families of human genes,” Shaw says. “Sometimes the gene performing a particular role will change, but the task will still be handled by a gene in the same family.”

When the scientists looked for the human version of the newly identified fly marker for sleep deprivation, they found ITGA5 and realized it hadn’t been among the human immune genes they screened at the start of the study. Testing ITGA5 activity in the saliva samples revealed that its activity levels increased during sleep deprivation.

“We will need more time to figure out how useful this particular marker will be for detecting sleep deprivation in humans,” Shaw said. “In the meantime, we’re going to continue jumping between our flies and humans to maximize our insights.”

Funding from the National Institutes of Health, Heart, Lung, and Blood Institute (HL092731) and Neurological Disease and Stroke (NS051305), and the W.M. Keck Foundation supported this research.

Thimgan MS, Gottschalk L, Toedebusch C, McLeland J, Rechtschaffen A, Gilliland-Roberts M, Duntley SP, Shaw PJ. Cross-translational studies in humans and Drosophila identify markers of sleep loss.PLoS ONE 8(4): e61016. doi:10.1371/journal.pone.0061016.

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Gelberman, Wertsch to receive 2013 faculty achievement awards

2013-05-02 00:00:00

Richard H. Gelberman, MD, a world-renowned expert in hand and wrist microsurgery, and James V. Wertsch, PhD, founding director of one of the most successful and innovative global scholarship programs in the world, will receive the university’s 2013 faculty achievement awards, Chancellor Mark S. Wrighton announced.

Wertsch

Gelberman

Gelberman, the Fred C. Reynolds Professor and head of the Department of Orthopaedic Surgery, will receive the Carl and Gerty Cori Faculty Achievement Award. Wertsch, vice chancellor for international affairs, director of the McDonnell International Scholars Academy and the Marshall S. Snow Professor in Arts & Sciences, will receive the Arthur Holly Compton Faculty Achievement Award.

They will receive their awards and give presentations of their scholarly work during a Dec. 7 program.

“I am pleased that we are recognizing two of Washington University’s most distinguished scholars with the 2013 faculty achievement awards,” Wrighton said. “Both recipients have enjoyed rewarding, productive careers and both have contributed significantly to the university. I join with the faculty of Washington University in congratulating Dr. Gelberman and Dr. Wertsch on this impressive honor.”

Richard Gelberman

When Gelberman joined the School of Medicine faculty in 1995 as the first head of orthopaedic surgery, the department included 14 full-time faculty, had no NIH-funded research and was ranked 48 of 50 orthopaedic surgery departments included in U.S. News & World Report rankings.

Following years of a concerted effort to add top-tier clinicians and researchers, the department, under Gelberman’s leadership, now has 48 faculty members, is ranked in the U.S. News top 10 and, with more than $5 million in annual grant support, has more NIH funding than any other orthopaedic surgery department in the United States.

Gelberman, who is also orthopaedic surgeon-in-chief at Barnes-Jewish and St. Louis Children’s hospitals, is a past president of the American Academy of Orthopaedic Surgeons and the American Society for Surgery of the Hand.

He studies connective tissue — the ligaments, tendons and muscles that allow us to move — and much of his NIH-funded research focuses on tendon healing. He also investigates fractures in the wrist, carpal tunnel syndrome and nerve injuries.

Born in New York, Gelberman grew up in Asheville, N.C. He is a graduate of the University of North Carolina at Chapel Hill and earned his medical degree from the University of Tennessee College of Medicine in Memphis.

He did his residency in orthopaedic surgery at the University of Wisconsin and fellowships in hand and microvascular surgery at Duke University Medical Center and in pediatric orthopaedic surgery at Boston Children’s Hospital.

He is a graduate of the Executive Program at Stanford University’s Graduate School of Business and has an honorary master’s degree from Harvard Medical School.

Among his honors, he was elected to the Institute of Medicine of the National Academies in 2003 and he received the Distinguished Clinician Educator Award from the American Orthopaedic Association in 2008.

The author of more than 250 scientific papers and editor of three books and 25 book chapters, he also serves on the editorial boards of eight medical publications.

James Wertsch

Wertsch has led the McDonnell International Scholars Academy since its inception in 2005. The academy’s mission is to develop future global leaders by recruiting outstanding graduates of leading research partner institutions from around the world for PhD or professional degree programs at WUSTL.

Under Wertsch’s leadership, the McDonnell Academy has grown from having 15 leading Asian universities as partners to having 28 leading universities from around the world as partners.

In addition to his work with the McDonnell Academy, he holds faculty appointments in anthropology, education, international and area studies, and psychology, all in Arts & Sciences.

Since joining WUSTL’s faculty in 1995 as professor and chair of the Department of Education, he has played a major role in developing several areas of research and teaching in Arts & Sciences, including the International and Area Studies Program.

A fellow in the American Academy of Arts and Sciences, Wertsch is an expert on collective memory and identity. He has particular interest in how these issues play out in Russia, Estonia and the Republic of Georgia.

He is working on several projects in the Republic of Georgia, including collaboration with colleagues on efforts to understand the emergence of civil society and democracy in Russia and other countries of the former Soviet Union, as well as in the United States.

After earning a PhD from the University of Chicago in 1975, Wertsch spent a year as a postdoctoral fellow in Moscow, where he studied linguistics and neuropsychology. He then went on to hold faculty positions at Northwestern University, the University of California, San Diego, and Clark University.

Wertsch holds honorary degrees from Linköping University in Sweden and the University of Oslo, and he is an honorary member of the Russian Academy of Education.

He is a guest professor at the University of Oslo, Tsinghua University in Beijing and Fudan University in Shanghai.

Scientists assemble genetic playbook for acute leukemia

Caroline Arbanas — 2013-05-01 00:00:00

Benjamin Raphael, Brown University

Lines in the circos plot connect major genes involved in acute myeloid leukemia with patients whose leukemia cells have mutations in those genes. For an interactive version of the graphic, click here.

A team of researchers led by Washington University School of Medicine in St. Louis has identified virtually all of the major mutations that drive acute myeloid leukemia (AML), a fast-growing blood cancer in adults that often is difficult to treat.

The findings, published online May 1 in The New England Journal of Medicine, pave the way for developing better treatments for AML based on the genetic profile of a patient’s cancer. They also could lead to ways to more accurately predict the severity of disease in individual patients.

“We now have a genetic playbook for this type of leukemia,” says study co-leader Timothy Ley, MD, the Lewis T. and Rosalind B. Apple Professor of Oncology in the Department of Medicine. “We don’t know all the rules yet, but we know all the major players. This information can help us begin to understand which patients need more aggressive treatment right up front and which can be treated effectively with standard chemotherapy.”

Some 200 patients newly diagnosed with AML were involved in the study, funded by the National Institutes of Health (NIH) as part of The Cancer Genome Atlas project. Nearly 150 researchers were involved in the effort.

A second Cancer Genome Atlas paper will be published May 2 in Nature. That research, also led by Washington University and focusing on endometrial cancer, shows that adding genomics-based testing to the standard diagnostic workup could change the recommended course of treatment for some women.

For the leukemia study, the scientists sequenced the DNA of each patient’s leukemia cells and compared the data to DNA from each patient’s healthy cells. In this way, they found the mutations that only occurred in the cancer cells and contributed to the development and progression of AML in each patient. They also looked for defects in RNA (a close chemical cousin of DNA) and other changes that alter the expression of genes without actually changing the DNA.

“These results provide important new insights into the genomics of a deadly and difficult-to-treat cancer, and underscore the power and scope of The Cancer Genome Atlas project,” says NIH Director Francis S. Collins, MD, PhD.

Compared to other adult cancers, AML is caused by relatively few mutations, the new study shows. Cancer cells in the AML patients had an average of 13 mutated genes, far fewer than the several hundred typically found in breast, lung and other solid tumors.

By studying a large number of AML cases, the scientists predict they have found nearly all of the major mutations that occur in patients with the disease.

“If only 5 percent of AML cases have a particular gene that is mutated, there is a greater than 99 percent chance that we encountered that mutation at least once in this study,” says co-leader Richard K. Wilson, PhD, director of Washington University’s Genome Institute and research member of the Siteman Cancer Center. “There are still rare mutations that remain to be discovered, but we expect they will fall into the same genetic pathways or gene sets that we identified as being very strongly associated with AML.”

An accompanying editorial by David Steensma, MD, at Dana-Farber Cancer Institute and Harvard Medical School in Boston, compares the new survey of leukemia genomes to Meriwether Lewis' and William Clark's expedition of the American frontier, an exploration with long-lasting influences. Both endeavors began in St. Louis and while the survey of AML cancer genomes is largely completed and similar projects for other cancers will soon conclude, Steensma writes, “the use of genomics in the [everyday] practice [of medicine] is just beginning.”

The researchers found more than 1,800 genes that were mutated at least once in the 200 samples, a discovery that hints at the many different routes that lead to AML. But only 23 of the genes were significantly mutated, and another 237 were mutated in two or more of the samples.

“We didn’t realize how few recurrent mutations there were, and no one was thinking even a few years ago that AML was associated with a high frequency of mutations in genes that encode epigenetic modifiers,” says Ley, who also is director of the embryonic stem cell core at the Siteman Cancer Center and professor of genetics. “This new information helps narrow the search for likely drug targets and markers that can help predict the severity of AML.”

To make sense of their findings, the researchers organized the genes into nine categories based on their function or the known pathways involved. These include tumor suppressor genes, signaling genes and epigenetic modifiers, the latter of which is the most frequently mutated class of genes in the study. Epigenetic changes influence when genes are turned on and off but don’t alter the DNA sequence.

To their surprise, the scientists identified patterns of cooperation and mutual exclusivity between certain genes or sets of genes. For example, a combination of mutations in three genes – FLT3, NPM1 and DNMT3A – were fairly common in patients and may represent a unique subtype of AML.

An estimated 14,600 Americans will be diagnosed with AML this year and some 10, 400 will die. Unfortunately, few good markers exist to help guide treatment decisions for many patients.

Benjamin Raphael, Brown University

The dark lines in the image show all the major mutations for acute myeloid leukemia that occurred in one patient with the disease.

Doctors routinely assess the severity of AML by looking at patients’ leukemia cells for broken or rearranged chromosomes, an indicator of very aggressive cancer. But more than half of all AML patients fall into a diagnostic category called “intermediate risk.” Their cancer cells have chromosomes that look normal or have very minor changes. And while some do well on standard chemotherapy, many others do poorly, underscoring the critical need for better ways to determine prognosis.

“Anything we can do to improve risk classification in this disease is really important because there is a cure for some patients – a stem cell transplant from a matched donor – but it is risky and costly and should only be used in patients who need it,” Ley says. “For these patients, it’s crucial to get the transplant early in the course of the disease.”

Ley, Wilson and their colleagues at The Genome Institute pioneered cancer genome sequencing. Since the Washington University team published the first cancer genome in 2008, the team has found many genetic mutations linked to AML and other tumors that never would have been suspected to be associated with cancer.

Now that scientists have a more complete list of genes altered in AML, the researchers expect other researchers will begin examining AML patient samples banked at their own institutions to understand the relationship between the mutated genes and treatment outcomes.

“We’ve never had such a complete picture of AML,” says Wilson. “Now, researchers can mine this data to determine whether individual mutations or sets of mutations can be used to predict prognosis or be targeted by new or existing drugs.”

Ley, T, Wilson R, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. The New England Journal of Medicine. Online May 1, 2013.

The research was funded by the National Institutes of Health (NIH). Grant numbers U24CA143845, U24CA143858, U24CA144025, U24CA143882, U24CA143866, U24CA143867, U24CA143848, U24CA143840, U24CA143835, U24CA143799, U24CA143883, U24CA143843, U54HG003067, U54HG003079, U54HG003273, and P01CA101937). Additional support came from the Barnes-Jewish Hospital Foundation.

Genomics to reshape endometrial cancer treatment

Caroline Arbanas — 2013-05-01 00:00:00

Robert Boston

Scientists at Washington University's Genome Institute have shown that adding genomics-based testing to the standard diagnostic workup for endometrial cancer could change the recommended treatment for some women.

The most in-depth look yet at endometrial cancer shows that adding genomics-based testing to the standard diagnostic workup could change the recommended course of treatment for some women.

The new research, involving nearly 400 women with cancer of the lining of the uterus, was published May 2 in the journal Nature. The endeavor is part of The Cancer Genome Atlas project, funded by the National Institutes of Health.

The study also indicates that some endometrial tumors are genetically similar to subtypes of ovarian cancer and deadly basal-like breast cancer. Future clinical trials should evaluate whether some endometrial cancers could be treated with drugs typically used for the other cancers, said project co-leader Elaine Mardis, PhD, co-director of The Genome Institute at Washington University School of Medicine in St. Louis. The other co-leader is Douglas A. Levine, MD, of the Memorial Sloan-Kettering Cancer Center.

A second Cancer Genome Atlas paper was published May 1 in The New England Journal of Medicine. That research, also led by Washington University, describes finding virtually all the major mutations involved in acute myeloid leukemia.

While gynecologic oncologists have long recognized two subtypes of endometrial cancer, one more aggressive than the other, the new data reveal four novel subtypes and also suggest that the frequency of mutations in a tumor could be used to help guide treatment decisions.

“We are entering an era when tumors can be evaluated from a genomics standpoint, not just by looking at cancer cells under a microscope,” said Mardis, also a professor of genetics and a research member of the Siteman Cancer Center. “This more comprehensive approach provides a clearer picture of the way particular endometrial cancers will behave and will be important to gynecological oncologists who treat this disease.”

As part of the new research, a consortium of researchers analyzed tumors from 373 women with endometrial cancer using different technologies to look for defects in DNA, RNA (a close chemical cousin of DNA) and proteins.

Their analysis indicates that about 25 percent of women with endometrial cancer who are thought to have a favorable prognosis based on pathology reports instead have a more formidable form of the disease, based on underlying genetic changes, and should be treated aggressively.

Clinically, endometrial cancers fall into two categories: endometrioid and serous. Endometrioid cancers generally are associated with excess estrogen, obesity and a favorable prognosis. In contrast, serous endometrial cancers are more common in older women and generally have poorer outcomes.

After surgery to remove endometrial cancer, women with the endometrioid subtype typically are treated with radiation therapy to kill remaining cancer cells, while those with serous tumors receive a more aggressive treatment – chemotherapy.

Doctors distinguish between the two tumor subtypes by evaluating cancer cells under a microscope. But categorizing some tumors is difficult, and pathologists don’t always agree.

Looking closely at endometrioid tumors classified as high-grade, meaning they are more likely to grow quickly and spread, the investigators showed that many share genetic features with serous tumors. These include frequent mutations in TP53, a tumor suppressor gene, as well as extensive copy number alterations, which refer to a cell having too many or too few copies of a gene.

“This highlights the benefit of digging deeper to find the genetic drivers of cancer growth,” Mardis said. “Even though high-grade endometrioid and serous endometrial cancer are different from a pathological standpoint, they are genetically very similar and may require a similar course of treatment.”

David Mutch, MD, Washington University

Until now, doctors have distinguished between the two known subtypes of endometrial cancer by evaluating tumor cells (above) under a microscope. The new research identified four novel subtypes of endometrial cancer and indicates that genomics-based testing can help determine which women need more aggressive treatment.

With a complete analysis of the tumor samples, the investigators identified four novel genomic-based subtypes of endometrial cancer, which set the stage for developing new ways to diagnose and treat the disease. The subtypes are based, in part, on the frequency of mutations in the tumors.

“The Cancer Genome Atlas' multidimensional approach to collecting genomic data, including clinical and pathology information, have made these findings possible,” said Harold Varmus, MD, director on the National Cancer Institute. “Without the integrated characterization of so many tumor samples, correlations between histology and genomic data may not have been observed or potential clinical outcomes identified.”

Interestingly, one subtype features an exceedingly high mutation rate in the POLE gene and, in this respect, is similar to an “ultramutated” subtype of colorectal cancer. But, surprisingly, patients with these kinds of tumors generally have good outcomes.

“Having many, many mutations sounds like a bad thing,” Mardis explained. “But these patients can’t fix the mistakes in their tumor DNA, so their cancer cells mutate themselves into oblivion before they have the opportunity to spread to other locations in the body. The good news for these patients is that their outcomes are excellent, and they don’t need aggressive treatment.”

Women with serous tumors frequently had mutations in one of two genes that potentially could be targeted with existing targeted therapies. Those with ERBB2 alterations, for example, may be effectively treated with Herceptin, a drug typically used in women with breast cancer who have the same mutation. Additionally, women whose endometrial tumors have PIK3CA mutations may benefit from drugs that inhibit the gene. Those drugs are now in phase II clinical trials.

According to the authors, the new findings provide a roadmap for future clinical trials for endometrial cancer.

“Each tumor subtype may warrant separate clinical trials because of marked genomic differences, which are indicative of different drivers of endometrial cancer,” Mardis said. “Developing therapies for each subtype may improve outcomes for many women with endometrial cancer and parallel what has been accomplished in breast cancer.”

Endometrial cancer is the fourth most commonly diagnosed cancer among U.S. women. About 50,000 cases will be diagnosed in 2013, and an estimated 8,000 women will die from the disease. For a majority of patients diagnosed with aggressive, high-grade tumors that have spread, the five-year survival rate is about 16 percent, though chemotherapy has been associated with improved survival, and new targeted agents are being tested.

The research is funded by the National Institutes of Health (NIH) as part of The Cancer Genome Atlas Project. Grant numbers: 5U24CA143799-04, 5U24CA143835-04, 5U24CA143840-04, 5U24CA143843-04, 5U24CA143845-04, 5U24CA143848-04, 5U24CA143858-04, 5U24CA143866-04, 5U24CA143867-04, 5U24CA143882-04, 5U24CA143883-04, 5U24CA144025-04, U54HG003067-11, U54HG003079-10 and U54HG003273-10.

Levine DA, Mardis ER and The Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature. May 2, 2013.

Obituary: Susan E. Lanzendorf, director of IVF lab, 54

Diane Duke Williams — 2013-04-30 00:00:00

Susan E. Lanzendorf, PhD, associate professor of obstetrics and gynecology and director of the in vitro fertilization lab at Washington University, died Tuesday, April 2, 2013, from complications of pancreatic cancer. She was 54.

Lanzendorf

Lanzendorf, a pioneer in the field of reproductive medicine, joined Washington University School of Medicine in 2002. Her early research led to advances in micromanipulation techniques and changed the treatment for male factor infertility. She mentored many young men and women professionally and academically and offered her guidance in the establishment of fertility clinics around the world.

“Susan was a key member of the Washington University Infertility and Reproductive Medicine Center,” said Randall Odem, MD, professor of obstetrics and gynecology and director of the Division of Reproductive Endocrinology and Infertility. “Her leadership and hard work will not be forgotten. She has helped make many of our patients become parents, and they will always be grateful.”

Lanzendorf earned a bachelor’s degree in biology from Virginia Commonwealth University in 1981 and a PhD in biology from Old Dominion University/Eastern Viriginia Medical School in 1987. Before joining Washington University, she served as director of gamete and embryo research at the Jones Institute for Reproductive Medicine in the Department of Obstetrics and Gynecology at Eastern Virginia Medical School.

Services were held April 6 at Oak Hill Funeral Home and Cemetery in St. Louis.

She is survived by her fiancé, Terrance Crocker; daughters Marie and Sophia Lanzendorf; her parents, Richard and Mildred Lanzendorf; and a brother, Michael (Joyce Ann) Lanzendorf. Another brother, Richard Lanzendorf Jr., died in 1983.

Memorial donations may be made to a charity of the donor’s choice.

Eberlein honored for support of female faculty

2013-04-29 00:00:00

Eberlein

Timothy Eberlein, MD, the Bixby Professor and Spencer T. and Ann W. Olin Distinguished Professor and chairman of the Department of Surgery at Washington University School of Medicine in St. Louis, has been named the inaugural winner of the Pillar of Support Award. The award was created by the Academic Women’s Network at the School of Medicine to recognize outstanding support of female faculty.

Eberlein, who also serves as director of the Alvin J. Siteman Cancer Center, received the award April 9 at the organization’s spring dinner.

“Dr. Eberlein has rightly earned the honor of the inaugural AWN Pillar of Support Award through his steadfast endorsement and mentoring of women,” said Susan E. Mackinnon, MD, the Sydney M. Jr. and Robert H. Shoenberg Professor and chief of the Division of Plastic and Reconstructive Surgery. “He not only listens to the concerns of female residents, fellows and attendings, he acts on their concerns. He has provided the resources and support needed to allow new, full-time mothers, both residents and attendings, to be full-time surgeons, mid-career mothers to lead national programs, and grandmothers to be members of the Institute of Medicine.

“While women have reached parity as members of our medical school classes, their advancement to the higher ranks in most medical fields has stalled. With his strong mentorship and sponsorship, Dr. Eberlein has given the women in the Department of Surgery a leg up and a push forward. Dr. Eberlein has set the AWN Pillar of Support bar at a high level and is most deserving of this important award.”

When Eberlein became chairman of the Department of Surgery in 1998, the department had three female faculty members. The department now has 37 women in its 141-member faculty. This includes six women who are professors of surgery, two of whom hold endowed chairs.

Further, about 35 percent of residents and 35 percent of fellows are women.

“It is very important for male leaders in academic medicine to feel comfortable mentoring women and helping them get into leadership positions themselves,” Eberlein said. “A number of years ago I looked at graduates of the top 10 medical schools in the country, and of the top 10 percent of graduates in those schools, 70 percent were women.

"It’s very obvious if you want the very best, then you have to make sure you have a place for women in leadership.”

Washington People: Ross Brownson

Leslie Gibson McCarthy — 2013-04-26 00:00:00

Joe Angeles

Brownson (left), president-elect of the American College of Epidemiology, talks with former student Carlos Mario Arango (MPH ’13). Brownson says that students keep him energized in his work, which involves developing solutions to some of today's most vexing public health problems.

In 1986, Ross Brownson, PhD, was an over-educated triathlete and store manager in Fort Collins, Colo., when he got a call from a former Colorado State University professor, who was heading up a division in the Missouri Department of Health.

“He said, ‘Ross, I have a job for you as a cancer epidemiologist if you’re willing to move to Missouri,’ ” Brownson says.

“I had never set foot in Missouri, but I said, ‘OK, I’ll take a chance on this.’ So I packed up and moved to Columbia.”

That Brownson, a native of Grand Junction, Colo., was selling running shoes and bicycles with a doctorate in his pocket wasn’t all that unusual.

“There may be more well-educated people working in retail and restaurants in Colorado than anywhere else in the world,” he says, “because there are great college towns and no one wants to leave the mountains.”

But leave the mountains for the Missouri plains he did, and Brownson, professor in both the Brown School and the School of Medicine at Washington University in St. Louis, has never looked back.

Calm, amiable, unflappable

Brownson spent eight years with the state health department, learning, as he says, how public health works in practice — combining his academic training with real-world policy development.

It was a combination, he says, that prepared him well for the next phase of his career — one that would launch him into becoming one of the country’s leading experts in chronic disease prevention and applied epidemiology.

His vitae has a long list of honors and awards; service experience; editorial boards and positions, including his joining the faculty at Saint Louis University (SLU) in 1994, and then moving to WUSTL in 2008. But his reputation speaks for itself. In September, Brownson will become president of the American College of Epidemiology after serving a one-year term as president-elect.

And it is his demeanor — calm, amiable, unflappable — that, when combined with his experience in both the public sector and academia, makes him uniquely situated to effect real change in public health from his office as co-director of the Prevention Research Center in St. Louis.

Building bridges

The center is distinctive in that it is a joint effort of WUSTL and SLU. Funded by the U.S. Centers for Disease Control and Prevention (CDC), its mission is to develop approaches to prevent chronic disease and improve health in high-risk communities. A large part of the work of Brownson’s teams has focused on understanding and promoting physical activity in the United States and Latin America.

“It’s unique in that we’re ‘co-located,’ ” Brownson says. “Universities are not naturally structured to collaborate effectively, but we’ve found a way of making this work and creating an excellent model for others.

“Both universities get the benefit of this kind of applied-prevention research. In addition to conducting the research and bringing in dollars to our institutions, we have opportunities to train students, partner with practitioners, and work with community members, so that we can ultimately improve people’s lives, which is what we are here to do.”

Brownson, who also is a faculty scholar at WUSTL’s Institute for Public Health, is building bridges everywhere — department to department, center to center, university to university. It’s this multidisciplinary approach to everything he does that endears Brownson to his colleagues — and to everyone he meets.

“Ross is widely known as not only one of the premier scholars in public health, but also one of the nicest human beings around,” says colleague Tim McBride, PhD, professor at the Brown School.

“He is a very generous person who is loyal, warm, and giving, and a great mentor to everyone, especially students and junior faculty,” says McBride.

Evidence-based practice

It was Brownson’s days in the public sector of the state that formed the basis for his research on evidence-based public health.

“I saw first-hand how much of public health practice was not evidence-based, wasn’t making the most effective use of the resources or making decisions based on the latest science,” he says.

Brownson cites an example. “When I started with the health department, we had no programs at all in cancer prevention. We did the estimates once and figured we were spending 3 percent of our public health dollars on chronic disease prevention — yet about 70 percent of the deaths were caused by chronic diseases.”

Brownson says the department didn’t abandon its traditional public health functions, such as maternal and child health and infectious disease control, but instead expanded its focus.

He was appointed as the first director of a new division focusing on chronic disease prevention.

“We raised the visibility (of chronic disease prevention) within the state, the governor’s office, and the legislature — in parallel with efforts at the CDC and the National Cancer Institute,” Brownson says.

“We consolidated existing programs and wrote grants to get new initiatives started.”

Energy and enthusiasm

Brownson says that’s where he realized that what you learn in school doesn’t always become reality when you’re out in practice. But he learned what had to change to makes things happen, and that’s been the basis of his prolific research in academia — at last count 325 articles and 11 books.

He cites two of them as being key texts in the public health arena: 2003’s Evidence-Based Public Health (with a second edition published in 2010) which “puts out the principles of what public health should be doing”; and 2012’s Dissemination and Implementation Research in Health: Translating Science to Practice, which, he says, spells out how to apply the vast evidence we have amassed on numerous topics in public health and medicine.

And what keeps him going – perhaps hearkening back to his student days at Colorado State – are the students themselves.

“I truly believe that being a college professor is the best job in the world,” Brownson says.

“At our research center, we get to hire the cream of the crop,” he says. “The students are unjaded and bring new energy and enthusiasm every year.

“I work with amazing staff and faculty colleagues who are solving the most vexing of public health issues.”

Women’s Society presents Switzer leadership awards, Danforth scholarship

Kelly Wiese Niemeyer — 2013-04-29 00:00:00

Three already accomplished young women received awards recently from the Women’s Society of Washington University (WSWU).

At the society’s annual membership meeting April 17, leaders announced the winners of the Harriet K. Switzer Leadership Award and the Elizabeth Gray Danforth Scholarship.

The Switzer award was presented to Jennifer Head and Melany Lopez; the Danforth scholarship was presented to Margarita Tisza.

The Switzer award is presented to graduating seniors who have made a significant contribution during their undergraduate careers at Washington University in St. Louis and demonstrate the potential for future leadership.

The Danforth scholarship is a full-tuition scholarship awarded annually to an outstanding community college transfer student.

Mary Butkus

Harriet Switzer, center, talks with the 2013 Harriet K. Switzer Leadership Award winners Jennifer Head, left, and Melany Lopez. The Women’s Society of Washington University bestowed the awards during its annual meeting April 17 in the Women’s Building Formal Lounge.

Head

Head is majoring in chemical engineering. She has been a top student and received several prestigious scholarships, in addition to her regular and varied involvement in community service.

Perhaps the project that made her stand out most, according to the leadership award committee, was her continued effort to improve conditions for children in Ethiopia.

Through Engineers without Borders, Head decided to work toward providing an adequate water supply for the Mekelle School for the Blind in North Ethiopia. After a campaign to raise awareness and funds, Head and other students along with faculty advisers traveled to the Mekelle School, ultimately repairing the water tower, installing a pump into a well and laying a water distribution network.

While working on this project, Head witnessed the devastating effects that vitamin A shortage has on Ethiopian children, causing blindness and increasing the mortality rate. She now plans to work to fortify local edible oils and flour with vitamin A. Head said she has won a Fulbright scholarship to pursue the vitamin A project and plans to spend nine months in Ethiopa next year doing so.

Head plans a career in global health and expects to pursue a master’s degree of public health in global environmental health at Emory University.

Lopez

Lopez, majoring in biology in Arts & Sciences, plans to become a doctor. During her undergraduate career, she has volunteered more than 2,500 hours with EST, the emergency medical technician student group on campus.

She has been an Annika Rodriguez scholar for four years and also has been a resident adviser.

She worked as a uSTAR (undergraduate student training in academic research) fellow in the cell biology and physiology lab of Associate Professor James Huettner, PhD, and they plan to submit their research results for publication soon.

Lopez was accepted in the Howard Hughes Medical Institute’s Exceptional Research Opportunities Program and worked last summer with David Clapham, MD, PhD, at Harvard Medical School and Boston Children’s Hospital.

Lopez also has been involved with Global Brigades, a student-run volunteer group that travels to developing countries to provide medical care and other services.

Mary Butkus

Florence Pullen, left, of the Women's Society of Washington University, and society president Tara Lewis visit with Margarita Tisza, this year's Elizabeth Gray Danforth Scholarship recipient. Tisza plans to pursue business degrees at WUSTL.

Tisza

Danforth scholarship recipient Margarita Tisza is completing her studies at St. Louis Community College-Meramec. She looks forward to pursuing bachelor’s and master’s degrees in accounting and in business administration at WUSTL.

Tisza has been an accomplished student as well as a student leader. She also works part-time and volunteers as a health care assistant with Paraquad, a nonprofit organization that provides services and advocacy for people with disabilities.

Membership in the Women’s Society is open to women of all ages from all backgrounds; WSWU does not require women to be associated with the university to join its organization.

Forum to highlight faculty flexibility benefits

Diane Duke Williams — 2013-04-26 00:00:00

Robert Boston

Bess Marshall, MD, associate professor of pediatrics, used the faculty career flexibility benefit of going part-time to care for her three young children and her father-in-law, who had suffered a debilitating heart attack.

Thirteen years ago, Bess and Loren Marshall, both MDs, were taking care of their three young children and Loren’s father, who had moved into their home because of a debilitating heart attack.

With so many family responsibilities, Beth Marshall, associate professor of pediatrics, thought she was going to have to quit work to manage it all. Instead, Alan Schwartz, MD, PhD, the Harriet B. Spoehrer Professor and head of the Department of Pediatrics, suggested Marshall use the faculty career flexibility benefit of going part-time.

“This option made it possible for me to keep working,” she said.

There are a number of faculty career flexibility benefits at Washington University School of Medicine, including working part-time, pausing during the tenure probationary period and phasing retirement.

To highlight career flexibility benefits, the Office of Faculty Affairs is hosting faculty forums on family resources, work-life fit and career paths from noon-1 p.m. May 6-8 in Schwarz Auditorium, which is on the first floor of the Maternity Building.

The program is free of charge to School of Medicine faculty and includes lunch. The forums will include panels of faculty who have participated in the benefits/programs, as well as staff from the Office of Human Resources. To register for a forum, follow this link.

Another faculty member, Sheila Stewart, PhD, associate professor of cell biology and physiology, chose the tenure probationary pause benefit to allow her to have an extra year to prepare her tenure package. “As a new mom, I didn’t know if I would need it, but I wanted to have the option,” Stewart said. “I didn’t need it as it turned out, but it was important to me that this benefit was available.”

Last fall, the School of Medicine was one of five schools nationally to receive a $250,000 Alfred P. Sloan Award for Faculty Career Flexibility. The grant aims to further improve career flexibility for academic physicians and scientists and develop future programs.

Diana Gray, MD, associate dean for faculty affairs and professor of obstetrics and gynecology and radiology, said she’s grateful that the medical school received support from the Sloan Foundation to increase faculty awareness of current policies and resources in addition to developing new tools for improved work-life balance.

“Medical school faculty have unique work-life challenges and need more flexibility to juggle the demands of their careers and personal lives,” Gray said. “We hope that the expanded support we provide will give our faculty greater satisfaction in their careers.”

As part of the grant, the medical school is developing a program in which peer mentors provide guidance and support to faculty who are starting families early in their careers. The funding also will establish a team to train peer mentors and faculty leaders to encourage career flexibility.

The medical school also is considering changes such as shared non-tenure faculty positions and part-time status on the tenure track.

Missing link in Parkinson’s disease found

Julia Evangelou Strait — 2013-04-25 00:00:00

Gerald W. Dorn II, MD

A mouse heart, in gray, shows signs of heart failure because it is missing Mfn2, newly identified as a key molecule in the process that culls unhealthy mitochondria from cells. Superimposed on the mouse heart is a fruit fly heart tube, shown in color. It also shows signs of failure because it is missing Parkin, another key molecule in mitochondrial quality control. These same molecules implicated in heart failure also play roles in Parkinson's disease.

Researchers at Washington University School of Medicine in St. Louis have described a missing link in understanding how damage to the body’s cellular power plants leads to Parkinson’s disease and, perhaps surprisingly, to some forms of heart failure.

These cellular power plants are called mitochondria. They manufacture the energy the cell requires to perform its many duties. And while heart and brain tissue may seem entirely different in form and function, one vital characteristic they share is a massive need for fuel.

Working in mouse and fruit fly hearts, the researchers found that a protein known as mitofusin 2 (Mfn2) is the long-sought missing link in the chain of events that control mitochondrial quality.

The findings are reported April 26 in the journal Science.

The new discovery in heart cells provides some explanation for the long known epidemiologic link between Parkinson’s disease and heart failure.

“If you have Parkinson’s disease, you have a more than two-fold increased risk of developing heart failure and a 50 percent higher risk of dying from heart failure,” said senior author Gerald W. Dorn II, MD, the Philip and Sima K. Needleman Professor of Medicine. “This suggested they are somehow related, and now we have identified a fundamental mechanism that links the two.”

Heart muscle cells and neurons in the brain have huge numbers of mitochondria that must be tightly monitored. If bad mitochondria are allowed to build up, not only do they stop making fuel, they begin consuming it and produce molecules that damage the cell. This damage eventually can lead to Parkinson’s or heart failure, depending on the organ affected. Most of the time, quality-control systems in a healthy cell make sure damaged or dysfunctional mitochondria are identified and removed.

Over the past 15 years, scientists have described much of this quality-control system. Both the beginning and end of the chain of events are well understood. And since 2006, scientists have been working to identify the mysterious middle section of the chain — the part that allows the internal environment of sick mitochondria to communicate to the rest of the cell that it needs to be destroyed.

“This was a big question,” Dorn said. “Scientists would draw the middle part of the chain as a black box. How do these self-destruct signals inside the mitochondria communicate with proteins far away in the surrounding cell that orchestrate the actual destruction?”

“To my knowledge, no one has connected an Mfn2 mutation to Parkinson’s disease,” Dorn said. “And until recently, I don’t think anybody would have looked. This isn’t what Mfn2 is supposed to do.”

Mitofusin 2 is known for its role in fusing mitochondria together, so they might exchange mitochondrial DNA in a primitive form of sexual reproduction.

“Mitofusins look like little Velcro loops,” Dorn said. “They help fuse together the outer membranes of mitochondria. Mitofusins 1 and 2 do pretty much the same thing in terms of mitochondrial fusion. What we have done is describe an entirely new function for Mfn2.”

The mitochondrial quality-control system begins with what Dorn calls a “dead man’s switch.”

“If the mitochondria are alive, they have to do work to keep the switch depressed to prevent their own self-destruction,” Dorn said.

Specifically, mitochondria work to import a molecule called PINK. Then they work to destroy it. When mitochondria get sick, they can’t destroy PINK and its levels begin to rise. Then comes the missing link that Dorn and his colleague Yun Chen, PhD, senior scientist, identified. Once PINK levels get high enough, they make a chemical change to Mfn2, which sits on the surface of mitochondria. This chemical change is called phosphorylation. Phosphorylated Mfn2 on the surface of the mitochondria can then bind with a molecule called Parkin that floats around in the surrounding cell.

Once Parkin binds to Mfn2 on sick mitochondria, Parkin labels the mitochondria for destruction. The labels then attract special compartments in the cell that “eat” and destroy the sick mitochondria. As long as all links in the quality-control system work properly, the cells’ damaged power plants are removed, clearing the way for healthy ones.

“But if you have a mutation in PINK, you get Parkinson’s disease,” Dorn said. “And if you have a mutation in Parkin, you get Parkinson’s disease. About 10 percent of Parkinson’s disease is attributed to these or other mutations that have been identified.”

According to Dorn, the discovery of Mfn2’s relationship to PINK and Parkin opens the doors to a new genetic form of Parkinson’s disease. And it may help improve diagnosis for both Parkinson’s disease and heart failure.

“I think researchers will look closely at inherited Parkinson’s cases that are not explained by known mutations,” Dorn said. “They will look for loss of function mutations in Mfn2, and I think they are likely to find some.”

Similarly, as a cardiologist, Dorn and his colleagues already have detected mutations in Mfn2 that appear to explain certain familial forms of heart failure, the gradual deterioration of heart muscle that impairs blood flow to the body. He speculates that looking for mutations in PINK and Parkin might be worthwhile in heart failure as well.

“In this case, the heart has informed us about Parkinson’s disease, but we may have also described a Parkinson’s disease analogy in the heart,” he said. “This entire process of mitochondrial quality control is a relatively small field for heart specialists, but interest is growing.”

This work was supported by the National Institutes of Health (NIH) grants R01 HL059888 and R21 HL107276.

Chen Y, Dorn GW. PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science. April 26, 2013.

Andrew Scharlach to discuss aging-friendly communities at Friedman lecture

Diane Duke Williams — 2013-04-25 00:00:00

Scharlach

Andrew Scharlach, PhD, the Eugene and Rose Kleiner Professor of Aging at the University of California, Berkeley, will deliver the 2013 Friedman lecture Friday, May 3, at the Eric P. Newman Education Center on the Washington University School of Medicine campus. The title of his lecture is “Creating Aging-Friendly Communities.”

The event, from 8:30 a.m. to noon, is free and open to the public. Check-in will begin at 8:30 a.m., followed at 9 a.m. with awards, the keynote address, a panel discussion, a poster session and refreshments.

Scharlach also is director of the Center for the Advanced Study of Aging Services at UC Berkeley. His work focuses on older adults and their families, particularly with regard to long-term care services, work and family responsibilities and aging-friendly communities. These are communities in which a range of transportation and social services are tailored to help people remain in their homes as they age.

He has conducted extensive research and evaluation of community aging initiatives, particularly the Village model, a movement in which seniors help seniors coordinate and deliver services within their communities. Scharlach is the principal investigator of a series of research projects aimed at increasing understanding of Village model programs and their potential for helping older adults age in place.

After the keynote, a panel discussion with Karen Berry-Elbert of the St. Louis Naturally Occurring Retirement Community (NORC), Arthur Culbert of the StL Village in the Central West End, and Camille Greenwald from the City of Richmond Heights will highlight local efforts to support and foster “aging in place.”

In addition, the Alene and Meyer Kopolow Award and the Dorismae and Harvey A. Friedman Award will be given at the event on behalf of the Harvey A. Friedman Center for Aging and The Foundation for Barnes-Jewish Hospital.

For more details and to register, follow this link.

2013 Spector Prize goes to two students

2013-04-26 00:00:00

Each year, the Department of Biology in Arts & Sciences at Washington University in St. Louis awards a prize to a graduating senior in memory of Marion Smith Spector, a 1938 WUSTL graduate who studied zoology under the late Viktor Hamburger, PhD.

Hamburger was a professor of biology and a prominent developmental biologist who made many important contributions while a WUSTL faculty member.

The Spector Prize, first awarded in 1974, recognizes academic excellence and outstanding undergraduate achievement in research. Students are nominated by their research mentors for outstanding research that has made substantial contributions to a field.

This year the prize has been awarded to two students, Megan Kelly and Jennifer Stevens, both of whom are majoring in biology.

Kelly

Kelly worked in the lab of Audrey Odom, MD, PhD, assistant professor of pediatrics and of molecular microbiology in the School of Medicine.

Kelly

"I originally planned to complete the premed courses and then apply to medical school," Kelly said. But the summer before I started college, I spent seven weeks in a lab as part of the Summer Scholars for Biology and Biomedical Research program.

I enjoyed it so much, I joined Dr. Odom’s lab that fall. And she filled me with a passion for science, giving me an opportunity to see what it’s like to be the first to discover something, to learn and to solve problems with science."

Kelly worked on the chemicals released by the parasites that cause malaria. The parasites synchronize their life cycles so that, for example, they all emerge from red blood cells into the bloodstream at the same time. In addition, mosquitos are more attracted to people infected with malaria than those that are not. Both observations suggest the parasites may be communicating by means of chemical signals.

"The object of my research was to figure out what the chemicals might be," Kelly said. "I used a fairly new method called SPME to sample the gas above the parasites ,and I found a class of chemicals called terpenes that had been previously unidentified in the malaria parasite.

"We think they may be responsible for some of these behaviors; we have already been able to show that mosquitoes can smell the terpenes," she said.

"Because of my experience working in Dr. Odom's lab, I realized I wanted to do science as well as medicine," she said.

Kelly plans to continue her work in Odom’s lab in the coming year, and then to begin a dual MD/PhD degree program in 2014.

Stevens

Stevens conducted her thesis research in the lab of Bruce Carlson, PhD, assistant professor of biology.

Stevens

“When I came to Wash U,” Stevens said, “I intended to go to medical school to become a physician. My first work-study assignment, however, was fish care in the Carlson lab.

"I had never really thought about research before, but as I attended lab meetings and interacted with others in lab, I began to realize how much fun research is. With Dr. Carlson’s unending encouragement, I started my own research project as a sophomore and became increasingly involved, until I ultimately decided to apply to dual-degree MD/PhD graduate programs last year."

Stevens studied the evolution of weakly electric fish in Carlson’s lab, concluding that fish species invested in either complex electrosensory systems or large eyes with good visual acuity, but not both.

This trade-off implies that species generally cannot specialize in multiple sensory systems simultaneously, she said. That might explain, for example, why bats that rely on echolocation for hunting tend to have poor eyesight and why people who lose their sight sometimes develop more acute hearing.

She plans to start the Medical Scientist Training (MD/PhD) Program at Washington University School of Medicine in June and intends to conduct her graduate work in neuroscience.

Kelly and Stevens presented their research at the Spector Prize seminar April 29 in Rebstock Hall.

As part of the Department of Biology’s recognition of their outstanding work, Kelly and Stevens will be recognized at the Biology Honors and Research Emphasis Reception, at 3:30 p.m. May 15 in McDonnell Hall, Room 162.

Obituary: Charles W. Parker, emeritus professor of medicine, 83

Michael C. Purdy — 2013-04-24 00:00:00

Charles Ward Parker, MD, a Washington University faculty member whose pioneering research helped improve treatment of allergies and asthma, died Tuesday, April 23, 2013, from pancreatic cancer at his home in Webster Groves. He was 83.

University Archives

Charles W. Parker

The emeritus professor of medicine served on the faculty at Washington University School of Medicine in St. Louis for more than four decades.

Parker grew up in Webster Groves and attended Washington University for his undergraduate and medical studies, graduating from the School of Medicine in 1953. Afterward, he did his residency in internal medicine at Barnes Hospital, and served as chief resident from 1958-59.

Parker’s mentor, Herman Eisen, PhD, professor emeritus at the Massachusetts Institute of Technology, noted that scholars who explore a variety of topics are often described as “foxes,” while those who explore one are “hedgehogs.”

“Charlie Parker was clearly a fox who contributed to our understanding of many aspects of the immune system,” Eisen said.

One of Parker’s major interests was allergy to penicillin.

“This was a very important clinical concern at the time because we didn’t have many alternative antibiotics that we could use in patients who had severe penicillin allergies,” said John Atkinson, MD, the Samuel Grant Professor of Medicine at Washington University, who did postgraduate work with Parker. “Dr. Parker developed the first tests for this allergy and worked on ways to decrease patients’ sensitivity to penicillin.”

In the early 1960s, Parker founded the Division of Allergy and Immunology in the Department of Internal Medicine. The division’s current director, H. James Wedner, MD, also studied under Parker as a postdoctoral fellow.

“He was an amazing thinker,” Wedner recalled. “He never forgot anything, and his ability to analyze and synthesize information was astounding. He was always finding something new and different, something nobody else had tried.”

When Wedner came to study under Parker, allergists were concerned about a missing link in their understanding of anaphylactic shock, the sudden, severe allergic reactions that can kill in minutes.

Parker determined that the link was a metabolite of arachidonic acid, a fatty acid found in the walls of every cell. This discovery made it possible to determine the structure of the molecule, which allowed it to be classified as a leukotriene, a family of signaling compounds now known to help regulate immune responses.

“The depth and breadth of Dr. Parker’s scientific contributions are quite remarkable,” said Victoria Fraser, MD, the Adolphus Busch Professor and chairman of the Department of Medicine. “In addition to his seminal contributions in penicillin sensitivity and identification of the leukotriene’s roles in allergy, he also developed a number of important radioimmunoassays, which are very sensitive tests that help us monitor critical biological compounds in research and in the clinic.”

Several of those tests still play important roles in the clinic, according to Fraser. One, known as the CPK-MB test,was one of the first tests to identify heart attacks. Another allows physicians to monitor the levels of medications known as digitoxins in heart patients.

Parker was a Howard Hughes Medical Institute investigator from 1977 to 1989. In 1983, Parker won Washington University’s Alumni Award. He became an honorary fellow of the American Academy of Allergy and Immunology in 1983.

Parker is survived by his wife of 59 years, Mary Langston Parker (WUSM MD ’53); his brother, Brent Parker, MD; children Charles S. Parker, MD; Christina Parker, MD; Katherine Parker Ponder, MD, a professor in the School of Medicine’s Division of Hematology; and Sandra Parker Bigg; and 15 grandchildren. One son, Keith L. Parker, MD, PhD, died in 2008.

A memorial service will be held at 3 p.m. Sunday, May 19, at the First Congregational Church of Webster Groves. A reception will follow.

Contributions may be sent to the Charles W. Parker Memorial Fund at the Division of Allergy & Immunology, c/o Jill Munoz, Washington University School of Medicine, 660 S. Euclid Avenue, Box 8122, St. Louis, Mo. 63116, or to the Webster Groves Public Library, in memory of Charles W. Parker, 301 E. Lockwood Ave.; Webster Groves, Mo. 63119-3102.

Memories and condolences may be left at www.gerberchapel.com.

ALS trial shows novel therapy is safe

Michael C. Purdy — 2013-04-23 00:00:00

Matthew J. Crisp

A mutated protein that causes an inherited form of Lou Gehrig's disease leads to clumps in the human cells in the bottom image. A therapy that blocks production of this protein has passed phase 1 safety trials.

An investigational treatment for an inherited form of Lou Gehrig’s disease has passed an early phase clinical trial for safety, researchers at Washington University School of Medicine in St. Louis and Massachusetts General Hospital report.

The researchers have shown that the therapy produced no serious side effects in patients with the disease, also known as amyotrophic lateral sclerosis (ALS). The phase 1 trial’s results, available online in Lancet Neurology, also demonstrate that the drug was successfully introduced into the central nervous system.

The treatment uses a technique that shuts off the mutated gene that causes the disease. This approach had never been tested against a condition that damages nerve cells in the brain and spinal cord.

“These results let us move forward in the development of this treatment and also suggest that it’s time to think about applying this same approach to other mutated genes that cause central nervous system disorders,” says lead author Timothy Miller, MD, PhD, assistant professor of neurology at Washington University. “These could include some forms of Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and other conditions.”

ALS destroys nerves that control muscles, gradually leading to paralysis and death. For treatment of the disease, the sole FDA-approved medication, Riluzole, has only a marginal effect.

Most cases of ALS are sporadic, but about 10 percent are linked to inherited mutations. Scientists have identified changes in 10 genes that can cause ALS and are still looking for others.

The study focused on a form of ALS caused by mutations in a gene called SOD1, which account for 2 percent of all ALS cases. Researchers have found more than 100 mutations in the SOD1 gene that cause ALS.

“At the molecular level, these mutations affect the properties of the SOD1 protein in a variety of ways, but they all lead to ALS,” says Miller, who is director of the Christopher Wells Hobler Lab for ALS Research at the Hope Center for Neurological Disorders at Washington University.

Rather than try to understand how each mutation causes ALS, Miller and his colleagues focused on blocking production of the SOD1 protein using a technique called antisense therapy.

To make a protein, cells have to copy the protein-building instructions from the gene. Antisense therapy blocks the cell from using these copies, allowing researchers to selectively silence individual genes.

“Antisense therapy has been considered and tested for a variety of disorders over the past several decades,” Miller says. “For example, the FDA recently approved an antisense therapy called Kynamro for familial hypercholesterolemia, an inherited condition that increases cholesterol levels in the blood.”

Miller and colleagues at the University of California-San Diego devised an antisense drug for SOD1 and successfully tested it in an animal model of the disease.

Merit Cudkowicz, MD, chief of neurology at Massachusetts General Hospital, was co-PI of the phase I clinical safety trial described in the new paper. Clinicians at Barnes-Jewish Hospital, Massachusetts General Hospital, Johns Hopkins Hospital and the Methodist Neurological Institute in Houston gave antisense therapy or a placebo to 21 patients with SOD1-related ALS. Treatment consisted of spinal infusions that lasted 11 hours.

The scientists found no significant difference between side effects in the control and treatment groups. Headache and back pain, both of which are often associated with spinal infusion, were among the most common side effects.

Immediately after the injections, the researchers took spinal fluid samples. This let them confirm the antisense drug was circulating in the spinal fluid of patients who received the treatment.

To treat SOD1-related ALS in the upcoming phase II trial, researchers will need to increase the dosage of the antisense drug. As the dose rises, they will watch to ensure that the therapy does not cause harmful inflammation or other side effects as it lowers SOD1 protein levels.

“All the information that we have so far suggests lowering SOD1 will be safe,” Miller says. “In fact, completely disabling SOD1 in mice seems to have little to no effect. We think it will be OK in patients, but we won’t know for sure until we’ve conducted further trials.”

The therapy may one day be helpful in the more common, noninherited forms of ALS, some of which may be linked to problems with the SOD1 protein.

“Before we can consider using this same therapy for sporadic ALS, we need more evidence that SOD1 is a major contributor to these forms of the disorder,” Miller says.

The trial was conducted with support from ISIS Pharmaceuticals, which co-owns a patent on the SOD1 antisense drug.

The clinical trial was funded by the Muscular Dystrophy Association, the ALS Association and Isis Pharmaceuticals.

Miller TM, Pestronk A, David W, Rothstein J, Simpson E, Appel SH, Andres PL, Mahoney K, Allred P, Alexander K, Ostrow LW, Schoenfeld D, Macklin EA, Norris DA, Manousakis G, Crisp M, Smith R, Bennett CF, Bishop KM, Cudkowicz ME. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised first-in-man study. Lancet Neurology, online May 29, 2013.

Graduate students recognize faculty mentors

2013-04-23 00:00:00

kevin lowder

The Graduate Student Senate at Washington University in St. Louis recognized eight faculty with Outstanding Faculty Mentor Awards during its 14th annual awards ceremony, held April 10 in the Women’s Building Formal Lounge. Five of the 2012-13 recipients are (from left) John M. Doris, PhD, professor of philosophy in Arts & Sciences; David Wang, PhD, associate professor of molecular microbiology and of pathology and immunology at the School of Medicine; David Balota, PhD, professor of psychology in Arts & Sciences; Wendy Auslander, PhD, the Barbara A. Bailey Professor of Social Work at the Brown School; and Lynne Tatlock, PhD, the Hortense and Tobias Lewin Distinguished Professor in the Humanities in Arts & Sciences. Not pictured are Gammon Earhart, PhD, associate professor of physical therapy; Nathan M. Jensen, PhD, associate professor of political science in Arts & Sciences; and Erik Trinkaus, PhD, the Mary Tileston Hemenway Professor in Arts & Sciences. The awards are based on nominations by graduate students and designed to honor faculty members whose dedication to mentoring PhD students and commitment to excellence in graduate training have made a significant contribution to the quality of life and professional development of students in the Graduate School of Arts & Sciences. Special recognition for excellence in mentoring went to six other faculty members at the ceremony. To see the list of faculty award winners, visit here.

New restaurant at Barnes-Jewish Center for Outpatient Health

2013-04-23 00:00:00

Shown is the new restaurant — Central Table — at the Barnes-Jewish Center for Outpatient Health.

Central Table, a new, 10,000-square-foot restaurant at the Barnes-Jewish Center for Outpatient Health, is scheduled to open for dinner Friday, May 1, and for all three meals May 6.

A coffee shop at the site already has opened. Its hours are 6 a.m. to 1:30 p.m.

A food hall modeled after food emporiums in New York and Los Angeles, Central Table will feature contemporary menus, distinct cooking stations and locally grown and produced ingredients when available.

During the day, Central Table will focus on convenience and efficiency for working professionals. At night, the tables will be set for dinner, and a full-service menu will be offered.

The restaurant will seat 200 people inside, including long tables for communal dining, private tables and seating at various cooking stations, such as the sushi bar. There also will be sidewalk seating for 75. The venue’s artisan market also will offer prepared foods to go.

As of May 6, the restaurant's hours will be 6 a.m. to 10 p.m. Monday through Thursday; 6 a.m. to 11 p.m. Friday and Saturday; and 6 a.m. to 9 p.m. Sunday.

Bacteria may contribute to premature births, STDs

Michael Purdy — 2013-04-22 00:00:00

Wandy Beatty

Gardnerella vaginalis, a common species of bacteria, may be an important contributor to bacterial vaginosis, a condition linked to preterm birth and increased risk of sexually transmitted diseases. Pictured is an individual G. vaginalis cell.

New research at Washington University School of Medicine in St. Louis points to a common species of bacteria as an important contributor to bacterial vaginosis, a condition linked to preterm birth and increased risk of sexually transmitted diseases.

The condition affects one in every three women, making it more common than yeast infections. But bacterial vaginosis often does not cause significant symptoms, leaving many women unaware they have it.

“Bacterial vaginosis can precipitate significant health problems, but it is not a common topic of conversation between patients and their gynecologists,” says Amanda Lewis, PhD, assistant professor of molecular microbiology. “Our findings, which come from new experimental models of the condition, may be a first step toward a better understanding of how to treat bacterial vaginosis and prevent serious complications linked with the condition.”

Bacterial vaginosis occurs when the typical mix of microbes in the vagina is knocked off-kilter. In some cases, bacterial vaginosis causes a change in the consistency of vaginal fluids and an unpleasant odor. The condition is diagnosed through examination of the vagina and tests of the vaginal fluids. Doctors typically treat it with antibiotics, but the condition often recurs.

Lewis and her colleagues recently published back-to-back papers on bacterial vaginosis, the first in Journal of Biological Chemistry and the second in PLOS One.

Dozens of bacterial species have been linked with bacterial vaginosis, leading to heated debates in the scientific community over which bacteria actually cause the condition and its complications. The new research provides evidence that mucus layers and cells lining the surface of the vagina are damaged in women with bacterial vaginosis and suggests that a single organism, Gardnerella vaginalis, is likely the cause.

G. vaginalis is commonly found in the vaginal fluids of women with bacterial vaginosis and in some women who don’t have the condition. The latter had led many researchers to dismiss the bacterium’s potential contributions to bacterial vaginosis.

Working in mice to simulate this condition, Nicole Gilbert, PhD, postdoctoral fellow, showed that G. vaginalis causes increased shedding of the outermost cells covering the vaginal lining.

“We think the vaginal lining is shed as part of the body’s effort to eliminate bacteria,” says Gilbert. “However, this shedding may also expose sensitive underlying tissues. This may be important for understanding why women with bacterial vaginosis are more susceptible to sexually transmitted diseases and urinary tract infections.”

Based on their observations in mice, the researchers compared vaginal samples from women with and without bacterial vaginosis and found that the outermost cells from the lining of the vagina are shed in higher numbers during bacterial vaginosis.

“This is the first time, to our knowledge, that the presence of increased numbers of shed cells has been detected in bacterial vaginosis in humans,” Lewis says. “These results also suggest that G. vaginalis is the cause of this increase.”

The researchers examined the ability of G. vaginalis to degrade mucus, which normally helps protect the vagina and uterus from infection.

Using biochemical approaches, Warren Lewis, PhD, research instructor in medicine, and Lloyd Robinson, PhD, research technician, showed that the bacterium uses an enzyme called sialidase to detach sialic acids, which are an abundant and important part of mucus.

The research team showed that the bacterium not only breaks up mucus barriers but also makes a meal of some of the components it frees from the barriers.

When the researchers tested vaginal mucus samples from women with bacterial vaginosis, they found lower levels of sialic acids than in women who did not have the condition. Mice also had lower levels of vaginal sialic acids after infection with G. vaginalis.

“This is the first time that a bacterium associated with vaginosis has been shown to participate in mucus degradation,” says Lewis. “This is significant because infection of the uterus is a common cause of preterm birth and likely requires degradation of the mucus plug, a physical structure that protects the pregnant uterus from bacteria in the vagina.”

Lewis WG, Robinson LS, Gilbert NM, Perry JC, Lewis AL. Degradation, foraging and depletion of mucus sialoglycans by the vagina-adapted actinobacterium Gardnerella vaginalis. Journal of Biological Chemistry, published online.

This work was supported by the March of Dimes, the Barnes-Jewish Hospital Foundation and the American Heart Association. The animal work was performed in a facility supported by a National Center for Research Resources grant C06RR012466.

Gilbert NM, Lewis WG, Lewis AL. Clinical features of bacterial vaginosis in a murine model of vaginal infection with Gardnerella vaginalis. PLOS One, published online.

This work was supported by the March of Dimes, the Barnes-Jewish Hospital Foundation, the American Heart Association and in part by NIH grant P50DK064540-11

‘Be a sponge’ and other advice to help students succeed at summer internships

Steve Givens — 2013-04-23 00:00:00

As students begin to leave campus for the summer, many will head off to internships, hoping to add to their classroom experiences and enhance their future opportunities by immersing themselves in the real world of work.

It’s a great way to spend the summer, said Mark Smith, Washington University in St. Louis’ associate vice chancellor for students and director of the Career Center, but to get the most out of the experience, it’s imperative that students have a clear plan.

“An internship can be the start of a great career, a way to make some money, a way to find out what you really like — and don't like — a way to confirm and fulfill your passions,” Smith said. “But you need to have a plan and the people you work with and for need to know about it.”

Essentially, Smith said, it comes down to these questions: What do you want to know about yourself, the industry in which you are working, and the function you are performing? And what can you can learn by the end of the summer and incorporate into your career planning and course choices when you return?

Smith offers four tips that will help make a summer internship more meaningful and productive.

1. It’s essential to communicate upfront to your supervisors what kinds of experiences you want to have before the end of the internship.

“Don't assume that the people you are working with will automatically know what you want,” Smith said. “You need to communicate the learning experiences and exposure you'd like to get in this very short time frame. Don't let past interns determine your summer. Your needs and goals are unique to you. Be professional, be clear, and don't give up. Most everyone at your firm is inclined to want to see you have a positive experience. Let them know what that experience looks like from your perspective.”

2. Find informal ways to meet others within the organization.

“Grab some coffee with folks you don't work directly with,” Smith said. “Set up lunches every week with people who are interesting to you, outside of your area. People love to talk about their work and careers — their achievements, their challenges, where they want to go next, and what they would recommend to you. By doing these things you will stand out, build a network of associates, and most importantly, learn what you need to know about where you want to direct your career passions when you return to school.”

3. Set high expectations and make the most of the experience, especially in the first four weeks.

“Be a sponge,” Smith said. “Do more than expected. Contribute in ways outside of the scope of the role they gave you. It will open opportunities that they, and you, hadn't considered at the beginning of your program. If you don't do this at the start, and you wait for the internship to evolve, you won't optimize your learning experience.”

4. Keep a journal and ask yourself questions such as:

• Do I really like working for this size of an organization?
• Is this type of organization the best way to start off my career?
• Would I want to spend eight hours a day working with people who do this kind of work?
• Would I be happy starting my career in a rigid culture that pays well, but which doesn't offer me the personal independence I am used to?
• Is it critical to get a graduate degree to be promoted in this industry?
• Where do those around me get their personal and professional satisfaction?
• How do professionals in this organization keep up with all the new developments?
• How do you get promoted in this industry?
• Which are the best organizations in this industry? Why are they the best?

Smith emphasizes that upfront planning and hard work are the keys to a successful internship.

“Every summer thousands of interns realize, too late, what they could have experienced, if they only communicated at the beginning what they wanted, and given 110 percent from Day One,” he said.

Dantas gets NIH Director's New Innovator Award

Michael C. Purdy — 2013-04-19 00:00:00

Gautam Dantas, PhD, has won a prestigious National Institutes of Health award for innovative research that may improve scientists' ability to keep the digestive system healthy.

Dantas

The award, called the NIH Director’s New Innovator Award, is part of the High Risk-High Reward program supported by the NIH Common Fund. Dantas’ award is funded by the National Institute of Diabetes and Digestive and Kidney Diseases.

Dantas, an assistant professor of pathology and immunology and of biomedical engineering, garnered attention last year for an analysis of antibiotic resistance genes that had exchanged between soil bacteria and disease-causing bacteria.

With support from the new award, Dantas plans to look for genes that can help beneficial microbes establish a lasting presence in the human gut as a potential treatment for digestive disorders.

“The community of microorganisms in our gut performs critical functions for us, including metabolizing carbohydrates, producing vitamins and keeping out harmful microbes,” Dantas said. “One way in which we could treat a disruption to this community is by ingesting probiotics, which are live microorganisms in pills or food that can provide a health benefit to us. But most current probiotic microorganisms cannot establish a permanent place for themselves in the human gut, limiting their benefit to the short term.”

Dantas is searching for genes from microbes naturally found in the human gut that can be engineered into probiotic microbes to allow them to better integrate themselves into and persist in a normal gut community, helping to extend the engineered probiotics’ beneficial effects.

Eberlein elected president of surgical association

Jim Goodwin — 2013-04-18 00:00:00

Eberlein

Timothy Eberlein, MD, chair of the Department of Surgery at Washington University School of Medicine in St. Louis, has been elected president of the Southern Surgical Association.

One of the nation’s leading medical groups, the association is dedicated to furthering the study and practice of surgery, especially in the Southern states.

“I am honored to be a part of such a prestigious medical group and to work with my fellow board members to advance the practice of surgery,” Eberlein said.

He is the only Southern Surgical Association officer in Missouri.

“The association is honored and fortunate to have such an accomplished leader as Dr. Eberlein as its president this year,” said James A. O’Neill Jr., MD, chairman of the council of the Southern Surgical Association. “We look forward to working with him for an additional five years when he joins the council at the end of his presidency.”

Eberlein also serves as Bixby Professor and Spencer T. and Ann W. Olin Distinguished Professor at Washington University School of Medicine, surgeon-in-chief at Barnes-Jewish Hospital and director of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

For more information about the Southern Surgical Association, visit www.southernsurg.org.

Symposium: Finding humanity in advanced dementia, April 27

2013-04-17 00:00:00

Rebecca L. BarNard

A Polaroid self-portrait hand-reworked by Rebecca L. Barnard, an artist, eerily foreshadows her oncoming illness, diagnosed 14 years later.

The Philosophy-Neuroscience-Psychology Program of Washington University in St Louis will host a symposium “Finding Humanity in Advanced Dementia” Saturday, April 27.

In this symposium, experts in the fields of patient care, psychology, philosophy, medicine, neuroscience, and a family caregiver discuss the effect of severe cognitive loss on people with dementia and those who care for them and seek to discover ways to honor the dignity of individuals coping with Alzheimer’s disease and other dementias.

Greg ruffing/redux

In December 2007, Richard Rubin and his wife, Beck (pictured above), already diagnosed with early-onset dementia, attended a lecture on “Cognitive Loss and Ethics” in Baltimore.

The young speaker asked whether a woman, faithful to her husband all her life, who started an affair in her nursing home, should be stopped. “Should you honor the wishes of a person in the early stages of dementia after she ceases to be a person,” the speaker asked.

Beck whispered to Richard, “He doesn’t know what he’s talking about,” and left the room.

A year later, Richard was struggling to keep Beck at home despite progressing dementia. In a moment of desperation, he tried to force her to take anti-psychotic medication. She backed away from him and slammed her head into the wall phone, which crashed to floor. Holding her head, she wailed, “Oh, Sweetie. Oh, Sweetie, I'm just a person! I'm just a person.”  

Richard Rubin will be the first speaker in the symposium “Finding Humanity in Advanced Dementia.”

The symposium will begin with a personal perspective presented by Richard M. Rubin, PhD, a lecturer in philosophy in University College (see sidebar).

Peggy Szwabo, PhD, a mental health consultant, then will discuss dementia caregiving from a clinical perspective.

She will be followed by Jason Karlawish, MD, professor of medicine, medical ethics and health policy at the University of Pennsylvania, and by Agnieszka Jaworska, PhD, associate professor of philosophy at the University of California at Riverside.

John C. Morris, MD, the Harvey A. and Dorismae Hacker Friedman Distinguished Professor of Neurology and director of the Alzheimer’s Disease Research Center, and Marcus E. Raichle, MD, professor of radiology, neurology, neurobiology and biomedical engineering, both at Washington University in St. Louis, will discuss biological aspects of dementia, and Raichle will present a case history from his own family.

All of the speakers, together with Rebecca Dresser, JD, the Daniel Noyes Professor of Law and professor of ethics in medicine at WUSTL, will take part in a panel discussion, and Carl Craver, PhD, professor of philosophy in Arts & Sciences at WUSTL, will deliver concluding remarks.

The symposium, which runs from 1 to 7:30 p.m. in Wilson Hall, Room 214, on the university’s Danforth Campus, is free and open to the public. Seating is limited, so pre-registration is enouraged. To register, email: wustldementiasymposium@gmail.com.

Futher details and additional resources for people struggling with dementia can be found at: https://pages.wustl.edu/dementiasymposium.

Irving Boime Symposium April 18

2013-04-16 00:00:00

Boime

The Irving Boime Symposium will be Thursday, April 18, at the Eric P. Newman Education Center, Seminar Room B, on the Washington University Medical Campus.

The symposium, which celebrates the prestigious career of Irving Boime, PhD, will begin at 9 a.m. and close about 5:30 p.m. The event, which is free and open to the public, is sponsored by the Office of the Executive Vice Chancellor for Medical Affairs and the departments of developmental biology and of obstetrics and gynecology.

Among the scheduled speakers are Boime; Larry J. Shapiro, MD, executive vice chancellor for medical affairs and dean of the School of Medicine; Lilianna Solnica-Krezel, PhD, professor and head of the Department of Developmental Biology; and George Macones, MD, the Mitchell and Elaine Yanow Professor and head of the Department of Obstetrics and Gynecology.

For, a complete schedule of speakers, follow this link.

Fish prone to melanoma get DNA decoded

Caroline Arbanas — 2013-04-15 00:00:00

Texas State University

Scientists have decoded the genome of platyfish, which are prone to developing melanomas (shown above) along the tail and fins.

Scientists at Washington University School of Medicine in St. Louis and elsewhere have decoded the genome of the platyfish, a cousin of the guppy and a popular choice for home aquariums.

Among scientists, the fish are meticulously studied for their tendency to develop melanoma and for other attributes more common to mammals, like courting prospective mates and giving birth to live young.

Known scientifically as Xiphophorus maculatus, platyfish sport a variety of spectacular colors – brilliant oranges, yellows and a lovely iridescent silver – and myriad striped and speckled patterns. And when melanomas develop, they are easy to spot, even to an untrained eye.

“In platyfish, melanomas typically develop as black splotches along the tail and fins,” said senior author Wesley Warren, PhD, a geneticist at Washington University’s Genome Institute. “These fish are an ideal model for exploring the many unknowns of cancer, including how, when and where it develops in the body as well as its severity.”

Scientists at Washington University, the University of Würzburg in Germany and Texas State University led an international team involved in sequencing and analyzing the platyfish genome. Their findings are available online in Nature Genetics.

“Now that we have the genome in hand, we can tease apart the way genes interact with one another to cause melanoma,” said co-lead author Manfred Schartl, PhD, of the University of Würzburg in Germany. “Just as in human melanoma, genes that play a role in pigment cells also influence the development of melanoma in platyfish.”

The platyfish genome includes some 20,000 genes, roughly the same number found in the human genome. But unlike humans and other mammals, the chromosomes of the platyfish, like those in other fish, have remained remarkably intact over some 200 million years of evolution.

“It’s very much a mystery as to why these chromosomes are so structurally similar among fish species over long time periods of evolution because they live in vastly different aquatic environments,” said Warren.

The platyfish is a prolific breeder. But while most fish lay eggs, platyfish females give birth to live young, often in broods of more than 100.

Comparing the genes of platyfish to those in mice and other mammals that give birth to their young, the scientists found a number of altered genes in the fish involved in live-bearing birth.

“Surprisingly, we found that the platyfish retain some yolk-related genes typically found in fish that lay eggs to produce their offspring, and genes involved in placenta function and egg fertilization displayed unique molecular changes,” says co-lead author Ron Walter, PhD, of Texas State University.

While humans are known for their higher-level thinking and behaviors, platyfish and other fish have evolved their own set of complex behaviors, like courting, schooling and avoiding predators that far exceed the abilities of amphibians, reptiles and other lower vertebrates. Looking through the platyfish genome, the researchers found a number of gene copies linked to cognition in humans and other mammals that could underlie these behaviors.

“These gene copies were retained at a high rate in the platyfish, which give them a chance to evolve different functions,” Warren explained. “In this case, we believe the extra gene copies gave platyfish and other related fish the ability to develop more complex behaviors, which is unexpected for many lower-level vertebrates.”

The research is funded by the National Institutes of Health, National Center for Research Resources and the Office of Research Infrastructure Programs.

Schartl M, Walter, RB, Shen Y, Garcia T, Catchen J, Amores A, Braasch I, Chalopin D, Volff J-N, Lesch K-P, Bisazza A, Minx P, Hillier L, Wilson RK, Fuerstenberg S, Boore J, Searle S, Postlethwait JH and Warren WC. The genome of the platyfish, Xiphophorus maculatus, provides insights into evolutionary adaption and several complex traits. Nature Genetics. March 31, 2013.

Awad named associate dean for medical student education

Elizabethe Holland Durando — 2013-04-15 00:00:00

Awad

Michael M. Awad, MD, PhD, has been named associate dean for medical student education at Washington University School of Medicine in St. Louis, effective June 1.

Awad is an assistant professor of surgery, program director of the university’s general surgery residency and director of the university’s Institute for Surgical Education.

“Medical education will undergo remarkable, transformative changes in the next five to 10 years,” Awad said. “Through its unique combination of an elite student body, a world-class faculty and forward-thinking administration, Washington University School of Medicine will be a national driver of these changes. It is truly an honor and a privilege to be a part of this outstanding educational program.”

In his new role in the Office of Medical Student Education (OMSE), Awad will oversee all aspects of the medical student curriculum, including managing schedules, evaluations, assessment, course planning and the Career Counseling office. He also will manage the Practice of Medicine courses and the fourth-year program. Further, he will be one of the leaders of the medical school’s Liaison Committee on Medical Education (LCME) accreditation process and act as a bridge for students and support faculty in obtaining recognition for their teaching.

“Dr. Awad has proven to be a wonderful colleague, possessing the highest levels of professionalism, dedication and compassion,” said Alison Whelan, MD, senior associate dean for education at the School of Medicine. “We look forward to working with him in his new role and are confident that he will do a superb job.”

Awad joined the School of Medicine faculty in 2009. His surgical and clinical specialties include minimally invasive surgery and robotic and endoscopic surgery.

He replaces David Windus, MD, who recently returned to full-time clinical practice at the School of Medicine.

Born in Boston, Awad earned bachelor’s, medical and doctoral degrees from Brown University, with his PhD in pathobiology. He was a visiting registrar at Oxford University and a resident at Johns Hopkins Hospital. He completed a fellowship in minimally invasive surgery, and he is currently working on a master’s degree in health professions education.

“Dr. Awad has quickly excelled in both his clinical and teaching duties while at the School of Medicine,” Whelan said. “He is a superb surgeon, clinician and teacher.”

Awad is a fellow of the American College of Surgeons. He also has received numerous awards and honors, including the Society of American Gastrointestinal Endoscopic Surgeons Career Development Award in 2011; a Washington University Top Ten Award in 2011; and the Samuel Wells Surgical Resident Teaching Award in 2010 and 2011. He was a recipient of a Carol B. and Jerome T. Loeb Teaching Fellowship for 2010–2012 for a project to create a novel, integrated residency and medical student online portal that helped improve trainee workflow and efficiency and transformed the educational trainee program.

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

MoDOT to remove Jefferson Avenue bridge over I-64/Highway 40

2013-04-15 00:00:00

Following the morning rush Thursday, April 18, the Missouri Department of Transportation will close the Jefferson Avenue bridge over Interstate 64/Highway 40 in preparation for the bridge’s removal the weekend of April 19-22.

Drivers will be able to use Compton Avenue, 18th Street and 14th Street to detour around the closure. A detour map can be found here.

All lanes and ramps on I-64/Highway 40 from Pine Street through Hampton Avenue will be closed about 8 p.m. Friday, April 19, to allow for the removal of the Jefferson Avenue bridge. However, crews will close the ramp from Pine Street to westbound I-64/Highway 40 earlier — at 7 a.m. Thursday, April 18.

MoDOT also expects to close all other area ramps onto westbound I-64/Highway 40 through early Monday, April 22, including the ramps from McCausland Avenue/Skinker Boulevard, Hampton and Kingshighway to eastbound I-64/Highway 40. The ramp from Pine to westbound I-64 will remain closed until Jefferson reopens in mid-July.

During the three-month bridge replacement project, crews also expect to close up to two lanes on I-64/Highway 40 in both directions weekdays between 9 a.m. and 3 p.m. They may close two lanes in both directions around the clock on weekends to minimize the amount of time the Jefferson Avenue bridge is closed. The right-hand lane on eastbound I-64/Highway 40 will become exit only to Jefferson.

MoDOT plans to have all available lanes and ramps open on eastbound I-64/Highway 40 at least an hour before any Cardinals home games and will try to keep all available lanes and ramps open westbound at least an hour after the end of home games.

WUSTL School of Medicine News

X Prize to provide incentive for Alzheimer’s cure

African-American health and well-being subject of new study in St. Louis area

Better detection for elephantiasis worm infection

Bear Cub grants foster entrepreneurship

Washington People: Catherine Appleton

Morris receives top Alzheimer’s Association honor

National Bike to Work Day is May 17​

I-CARES announces 2013 funded research projects

Three doctoral candidates named Bouchet Fellows

Alzheimer’s markers predict start of mental decline

Siteman's Komen St. Louis Race for the Cure team makes great strides against breast cancer

OT student receives leadership award

Scientists show how nerve wiring self-destructs

Obituary: Burton E. Sobel, MD, former director of Cardiovascular Division, 75

Siteman director appointed vice chair of national cancer network

Moley elected president of gynecologic society

Obituary: William H. Daughaday, former director of metabolism, 95

Nerve stimulation for severe depression changes brain function

Three faculty elected to National Academy of Sciences

New perspective needed for role of major Alzheimer's gene

Discovery helps show how breast cancer spreads

Elson elected fellow of arts and sciences academy

School of Medicine, SLCH and BJH nurses honored with 2013 Excellence in Nursing awards

School of Medicine commencement speakers

Author of book about the famed Cori Laboratory to open Cori Lecture May 8

Unusual comparison nets new sleep loss marker

Gelberman, Wertsch to receive 2013 faculty achievement awards

Scientists assemble genetic playbook for acute leukemia

Genomics to reshape endometrial cancer treatment

Obituary: Susan E. Lanzendorf, director of IVF lab, 54

Eberlein honored for support of female faculty

Washington People: Ross Brownson

Women’s Society presents Switzer leadership awards, Danforth scholarship

Forum to highlight faculty flexibility benefits

Missing link in Parkinson’s disease found

Andrew Scharlach to discuss aging-friendly communities at Friedman lecture​

2013 Spector Prize goes to two students

Obituary: Charles W. Parker, emeritus professor of medicine, 83

ALS trial shows novel therapy is safe

Graduate students recognize faculty mentors

New restaurant at Barnes-Jewish Center for Outpatient Health

Bacteria may contribute to premature births, STDs

‘Be a sponge’ and other advice to help students succeed at summer internships

Dantas gets NIH Director's New Innovator Award

Eberlein elected president of surgical association

Symposium: Finding humanity in advanced dementia, April 27

Irving Boime Symposium April 18

Fish prone to melanoma get DNA decoded

Awad named associate dean for medical student education

MoDOT to remove Jefferson Avenue bridge over I-64/Highway 40

National Bike to Work Day is May 17

Andrew Scharlach to discuss aging-friendly communities at Friedman lecture