Trishia Bermudez who underwent microarray while pregnant with her son, Matthew / Photograph by Jörg Meyer.

Columbia Magazine’s Spring 2013 issue includes a feature article about a National Institutes of Health-funded multicenter study, led by Ronald Wapner, MD, director of reproductive genetics at Columbia University Medical Center and vice chairman for research in the Department of Obstetrics and Gynecology, which provided thousands of pregnant women with microarray analysis, a powerful new genetic test, for prenatal testing. The purpose of his study was to determine if this test generates information that is useful to doctors and parents, and therefore should be offered to all expectant mothers. As written in the article by Claudia Kalb:

…Prenatal genetic testing emerged in the 1970s, when obstetricians started to recommend amniocentesis for pregnant women over the age of thirty-five. The first common condition that scientists learned to preemptively diagnose was Down syndrome, which stood out because it is caused by the presence of a whole extra chromosome. Soon, they were also spotting the large chromosomal anomalies that cause Tay-Sachs disease, sickle-cell anemia, and several disorders of the neural tube, which is the embryo’s precursor to the brain and spinal cord.

 

Wapner, a sixty-five-year-old obstetrician who came to Columbia from Drexel University in 2005, has been trying to improve prenatal diagnosis his entire career. In the early 1980s, he was instrumental in developing chorionic villus sampling (CVS), a procedure in which fetal cells are extracted from a woman’s placenta rather than from her amniotic fluid. CVS can be done at an earlier stage of pregnancy — in the first trimester, versus the second — and is now a popular alternative to amniocentesis, although some women still get amniocentesis because it is easier for physicians to administer and is more widely available.

 

Wapner’s most important contribution, though, may turn out to be his advancement of microarray analysis, the genetic test that Bermudez underwent last summer. The idea is simple: rather than limiting oneself to what can be spotted visually, why not use computers to identify the minutest discrepancies in a baby’s DNA? The technology is not new. By the time Wapner proposed examining fetal tissue this way in 2006, physicians had been analyzing the DNA of sick children by microarray for a few years. The technique was especially useful in spotting rare disorders that pediatricians had trouble diagnosing any other way.

 

“Say you have a youngster with a seemingly random combination of learning difficulties and physical problems, like a heart defect and cleft palate,” says Wapner. “If you do the microarray, you may discover he has a small piece of chromosome 22 missing. That indicates it’s DiGeorge syndrome. And it means he’s got a 25 percent chance of developing schizophrenia. So now you can be on the lookout for that, too.”

 

With such a sophisticated tool, however, came thorny ethical questions. Obstetricians knew from experience that many pregnant women who opt for genetic testing are those who, after having received a troubling result on an ultrasound, are considering abortion. The method of analysis using microscopes, which is called karyotyping, was generally considered a useful tool for helping them to make this decision because it identified large, clearly defined genetic defects. The microarray test, on the other hand, would detect not only the genetic signatures of rare diseases like DiGeorge syndrome but also many other DNA flaws whose impact on the body were not yet fully understood.

 

…“Imagine if parents and doctors knew from day one that a child was going to be susceptible to autism,” Wapner says. “They might catch it sooner and provide him early intervention, which can be critical. There are all sorts of things a physician can do with this information.”

Click here to read the full article in Columbia Magazine.

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Their report, in Science Translational Medicine, reveals that an over-active gene linked in 20 to 30 percent of patients with childhood asthma interrupts the synthesis of lipid molecules (known as sphingolipids) that are part of cell membranes found all over the body.

Although the researchers do not yet understand why asthma results from reduced production of sphingolipids, their experiments clearly show a link between loss of these lipids and bronchial hyperreactivity, a key feature of asthma.

What makes this pathway unique, investigators say, is that it is not related to allergens and, the investigators discovered, has nothing to do with inflammation.

“Usually asthma is thought to be an inflammatory disease or a reaction to an allergen. Our model shows that asthma can result from having too little of a type of sphingolipids. This is a completely new pathway for asthma pathogenesis,” says the study’s senior author, Dr. Stefan Worgall, chief of the Pediatric Pulmonology, Allergy and Immunology Division at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

This is very good news, he adds. “Our findings are not only valuable in understanding the pathogenesis of this complex disease, but provide a basis to develop novel therapies, especially asthma agents based on a patient’s genotype,” says Dr. Worgall, who is also a distinguished professor of pediatric pulmonology, professor of pediatrics and associate professor of genetic medicine at Weill Cornell Medical College.

Precision Medicine for Asthma

Asthma is a significant health problem affecting about 7 million children in the United States. Nearly 10 percent of American children 0–17 years of age have asthma, making it the most common serious respiratory childhood disease. Its prevalence is even higher among inner-city children, says Dr. Worgall. Besides causing suffering, disability and alarm, the economic toll is significant, he says: In 2009, asthma caused 640,000 emergency room visits and 157,000 hospitalizations, plus 10.5 million missed school days.

“Yet while it has become increasingly evident that asthma takes several forms, treatment of the disorder is uniform,” he says. “Most therapies are designed to reduce inflammation, but they do not help all sufferers.”

The notion that asthma has different forms gained ground after several genome-wide association studies (GWAS) found variation in a gene, later identified as ORMDL3, in to up to 30 percent of asthma cases. In 2007, over-production of the gene’s protein was connected to childhood asthma, and this gene has been the most consistent genetic factor identified so far for asthma.

In 2010, a study in yeast found that ORMDL3 protein inhibits sphingolipid de-novo synthesis.

This finding prompted the researchers to investigate whether sphingolipid production is connected to asthma. Their study shows that this is indeed true in mouse models of the disease. Using mouse models, the researchers found that inhibition of an enzyme, serine palmitoyl-CoA transferase (SPT), which is critical to sphingolipid synthesis, produced asthma in mice and in human airways, as it did in mice that had a genetic defect in SPT.

The airway hyperactivity seen in the mice was not linked to increased inflammation, and the scientists saw a decreased response of the lung and airways to magnesium — which is often used in emergency rooms to relieve chest tightness of patients with asthma attacks.

“In our mouse models, we found that magnesium was not effective at inducing airway relaxation, suggesting the same would be true for humans whose asthma is linked to ORMDL3,” says the study’s first author, Dr. Tilla S. Worgall, assistant professor in the Department of Pathology and Cell Biology and a member of the Institute of Human Nutrition at Columbia University Medical Center. “The association of decreased de novo sphingolipid synthesis with alterations in cellular magnesium homeostasis provides a clue into the mechanism of asthma. Therefore, therapies that circumvent the effect of the ORMDL3 genotype may be effective treatments for asthma sufferers. We are now working towards developing these new therapies.”

The paper is titled, “Impaired sphingolipid synthesis in the respiratory tract induces airway hyperreactivity.” Additional authors include Arul Veerappan, Biin Sung, Evan Weiner, Rheeshma Bholah and Dr. Randy B. Silverfrom Weill Cornell Medical College; Benjamin I. Kimfrom Columbia University Medical Center; and Dr. Xian-Cheng Jiang from SUNY Downstate Medical Center (formally known as The State University of New York at Brooklyn).

The study was funded by the Department of Pediatrics at Weill Cornell Medical College, and the Department of Pathology and Cell Biology and Institute of Human Nutrition at Columbia University Medical Center. This research was also supported by the Irving Institute for Clinical and Translational Research at CUMC, which is supported by the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program, through grant UL1 TR000040.

The authors declare no financial or other conflicts of interest.

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Weill Cornell Medical College, Cornell University’s medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances — including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson’s disease, and most recently, the world’s first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu.

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cumc.columbia.edu or columbiadoctors.org.

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NEW YORK — A thumb-sized sound processor worn behind the ear and held in place by a small, magnetized titanium implant inserted under the skin is now being offered at NewYork-Presbyterian/Columbia University Medical Center to people with single-sided sensorineural hearing loss and for those with conductive hearing loss who cannot wear conventional hearing aids.

“The Sophono Alpha 2 abutment-free, bone-anchored hearing system is for patients who cannot wear conventional hearing aids because of chronic ear infections or external auditory canal atresia, a condition where the ear canal is not fully formed or functional,” said Dr. Anil K. Lalwani, an otolaryngologist at NewYork-Presbyterian Hospital/Columbia University Medical Center.

Other devices for these patients tether in place by drilling a hole in the skull and installing a screw (abutment) that pokes through the skin on the side of the head. Patients then have to wait three months before the device can be used and often suffer from chronic skin infection around the abutment. “The Sophono Alpha device, which is abutment-free, is cosmetically more appealing as no apparatus comes through the skin. As a result, there is no issue of constant wound care, as the hearing aid is secured in place by magnets,” said Dr. Lalwani, who is also professor and vice chair for research in the Department of Otolaryngology—Head and Neck Surgery at Columbia University College of Physicians and Surgeons, and director of the Division of Otology, Neurotology and Skull Base Surgery and of the Cochlear Implant Center, Columbia University Medical Center.

Additionally, the Sophono can be used within two to four weeks after surgery, instead of the three months that is required with other devices.

The Sophono addresses a common problem for those with impaired hearing—distinguishing speech from background noise. “This is a huge issue even for people who have hearing loss in one ear. They have problems following a conversation in social settings, such as at restaurants or at parties, or in other noisy environments,” said Dr. Lalwani. Like fine-tuning a radio station to eliminate background static, the Sophono Alpha System enhances the auditory system’s ability to hear by improving the ratio of recognized speech to noise.

Hearing Device Bypasses Ear Canal Blockage

In people with normal hearing, sound waves, or vibrations, travel from the outer ear into the middle ear and eardrum, then make their way through three tiny bones into the cochlea, a snail-like coiled tube in the inner ear. Once inside the cochlea, the vibrations are picked up by thousands of specialized hair cells that convert them to an electrical signal. This signal is then sent to the brain by the auditory nerve and translated into hearing.

“The system functions much like a ‘work around’ in people with conductive hearing loss, which occurs when there is a blockage between the outer and inner ear,” said Dr. Lalwani. The external sound processor picks up the sound waves and amplifies them by activating the titanium implant, which vibrates the skull and sends a signal directly to the cochlea and then to the brain.

In environments with background distractions, technology embedded in the sound processor automatically detects and reduces unwanted noise from behind and amplifies speech in front, resulting in clearer communication.

In one-sided sensorineural hearing loss caused by nerve damage in the cochlea, the external sound processor picks up a sound wave—on either side of the head—triggering the titanium implant to vibrate the skull and transmit the sound to the ear with hearing. “This new system eliminates the need for those who are deaf in one ear to constantly turn their head toward the hearing side, which improves hearing and reduces frustration,” said Dr. Lalwani.

Hearing Device Implanted in Outpatient Procedure

People who are candidates for the Sophono Alpha System undergo an outpatient procedure to insert the titanium implant under the skin. Once the incision is healed, in roughly four weeks, an audiologist activates the external sound processor, which enables instant hearing.

In April 2013, the Sophono Alpha received clearance by the U.S. Food and Drug Administration (FDA) for use with magnetic resonance imaging (MRI). The Sophono Alpha also has passed ASTM International tests for MRI use.

NewYork-Presbyterian Hospital

NewYork-Presbyterian Hospital, based in New York City, is the nation’s largest not-for-profit, nonsectarian hospital, with 2,409 beds. The Hospital has nearly 2 million inpatient and outpatient visits in a year, including 12,758 deliveries and 215,946 visits to its emergency departments. NewYork-Presbyterian’s 6,144 affiliated physicians and 20,154 staff provide state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine at five major centers: NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian Hospital/Columbia University Medical Center, NewYork-Presbyterian/Morgan Stanley Children’s Hospital, NewYork-Presbyterian/The Allen Hospital and NewYork-Presbyterian Hospital/Westchester Division. One of the most comprehensive health care institutions in the world, the Hospital is committed to excellence in patient care, research, education and community service. NewYork-Presbyterian is the #1 hospital in the New York metropolitan area and is consistently ranked among the best academic medical institutions in the nation, according to U.S.News & World Report. The Hospital has academic affiliations with two of the nation’s leading medical colleges: Weill Cornell Medical College and Columbia University College of Physicians and Surgeons. For more information, visit www.nyp.org.

Columbia University Medical Center

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cumc.columbia.edu or columbiadoctors.org.

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Jiwon Lee, Columbia University College of Dental Medicine ’14, was elected president of the American Student Dental Association (ASDA) in March, after serving as speaker of the House of Delegates from 2012 to 2013. She is one of two appointed students to the Joint Commission on National Dental Examinations for 2012 to 2014.

In 2012, she was a voting delegate at the American Dental Association (ADA) Annual Session. Previously, she served her district as co­‐legislative liaison and her local chapter as co-‐vice president and fundraising chair.  Prior to dental school, Lee was an intern at NPR in Ann Arbor, Mich., and then a production assistant at national ABC News headquarters in New York. She also worked as an AmeriCorps sponsored Math Immersion Teaching Fellow for New York City middle school students.

“I am incredibly proud to represent my fellow dental students as their president,” said Lee.  “I truly believe that ASDA has the power to inspire change for both patients and the leaders we create.”

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THE SECOND BRAIN

Columbia University Professor Michael Gershon calls the stomach a “second brain” because it can operate without any input from the brain or spinal cord. His research focuses on the connections between the brain and the digestive system.

“[The gut] is not a second brain in the sense that it deals with religion, philosophy, or politics,” Dr. Gershon says. “It leaves that to the brain in the head. But it deals with the messy, dirty business of digestion.”

Ideally, the gut and the brain have a working relationship that’s active yet so quiet the communication does not reach our consciousness. Dr. Gershon describes the well-performing brain as a “benevelent CEO” that does not micromanage, but instead simply signals when the stomach needs to do more or less. In turn, the stomach should be the kind of worker that doesn’t disrupt the boss.

“The gut is not an organ from which you wish to receive frequent progress reports,” he says. “You want the enteric nervous system to function in the deep background.”

THAT BUTTERFLY FEELING

What’s happening when the butterflies arrive, Dr. Gershon says, is simply anxiety. The once benevolent CEO brain turns into an overbearing CEO, kicking the stomach into high gear, telling it to act more, secrete more.

“And because pressure is increased in the gut, sensory nerves in the gut send signals of discomfort back to the brain. This may cause frequent bowel movements or just queasiness in the stomach, but that’s the sensation,” Dr. Gerson explains. “Physically the gut is pressing and twisting and just tying itself into knots, essentially, too strongly. And that sends signals back to the brain, too strongly.”

Feeling butterflies in your stomach is completely normal—especially during times of transition like graduating or starting a new job.

The most crucial step in chasing them away is to recognize them for what they are: anxiety. Once you have recognized the problem, Dr. Gershon advises analyzing what the cause may be and then, if the problem persists, considering getting help to ease the symptoms.

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Distinguished Service Awards

The Distinguished Service Awards recognize individuals who have served the College of Physicians & Surgeons with the greatest distinction, bringing honor to the institution, to its alumni, and to the profession itself.

Linda Lewis, MD

Andrew Wit, PhD, professor emeritus and special lecturer in pharmacology, for outstanding teaching during his career and for contributions to the study of cardiac arrhythmias.

Linda Lewis, MD, clinical professor emeritus and special lecturer in neurology, for her 26 years as dean of student affairs and her clinical expertise.

Charles W. Bohmfalk Awards

Penelope Boyden, PhD

The Charles W. Bohmfalk Awards were established through the generosity of John Frederick and Alice Bohmfalk in memory of a graduate of the P&S Class of 1884. The awards recognize distinguished teaching in the pre-clinical and in the clinical years.

Penelope Boyden, PhD, professor of pharmacology, for her devotion to teaching medical students in the pre-clinical years and innovative course design.

Deborah P. Jones, MD, assistant clinical professor of medicine, for her innovation, leadership and clinical skill in her role as primary care clerkship director.

Dr. Harold & Golden Lamport Research Awards

The Dr. Harold and Golden Lamport Research Awards were initiated in 1983 to honor outstanding young researchers in the basic and clinical sciences.

Randy Bruno, PhD

Randy M. Bruno, PhD, assistant professor of neuroscience, for his research elucidating how sensory information is processed by the brain to generate central representations of the external world.

Christian Schulze, MD, Florence Irving Assistant Professor of Medicine, for his clinical research that has demonstrated changes in circulating levels of adipocytokines in patients with heart failure.

Leonard Tow Humanism in Medicine Award

Emily DiMango, MD

The Leonard Tow Humanism in Medicine Award from the Arnold P. Gold Foundation is presented each year to a physician who has demonstrated compassionate and devoted patient care and who is a humanistic role model for students and young physicians.

Emily DiMango, MD, associate professor of medicine, for her tireless work addressing the needs of people with asthma in Washington Heights and leading the Adult Cystic Fibrosis Program, which has become a national model for excellent and compassionate care.

Stevens Triennial Prize

Carol Ann Mason, PhD

The Stevens Triennial Prize was established in 1891 by Alexander Hodgen Stevens, MD, a former president of P&S, and is awarded to an individual whose research is deemed to be the most meritorious.

Carol Ann Mason, PhD, professor of pathology & cell biology, neuroscience, and ophthalmic science, for her research on cell-to-cell interactions in the developing brain, which has been recognized by her election to the Institute of Medicine and as president of the Society for Neuroscience.

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Michael Devlin, MD

The P&S Class of 2013 has selected Michael Devlin, MD, professor of clinical psychiatry, to receive the Distinguished Teacher Award at Commencement on May 22.

Devlin is the founder and director of the Clinical Practice III course for students in the major clinical year. This innovative course combines the elements of reflective practice, longitudinal integration of clinical clerkships, and individual mentoring, all of which he believes to be of critical importance to the development of effective medical professionals.

There are many outstanding teachers at P&S, says David Bejar’13, but Dr. Devlin connects with people on a deeper, personal level.

“He teaches by example. By interacting with him, either formally in lecture or informally through conversation, you learn not only the virtues that make a good doctor, but also a good person in general: kindness, humility, patience, and dedication,” Bejar says.

“It is clear from his demeanor when interacting with students in lectures or in small group sessions that he enjoys teaching. He is an engaging, thoughtful, kind and patient professor – and it is a true pleasure to be his student.”

Devlin is a 1982 graduate of P&S and completed his psychiatry residency at Columbia University Medical Center/New York State Psychiatric Institute. Following his residency, he joined the Eating Disorders Research Unit at NYSPI where he works with patients with eating disorders and conducts clinical research.

In addition to his role in medical student education, Devlin also is active in the training and supervision of psychiatry residents, particularly in cognitive behavioral therapy. He is a member of the Virginia Apgar Academy of Medical Educators at P&S, an organization of select P&S faculty members that promotes faculty development and curriculum innovation.

Devlin was selected Distinguished Teacher by the P&S Class of 2011 and has received teacher of the year awards from third-year medical students (2007) and residents in psychiatry (2002).

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Tener Huang, a 2013 graduate of the dental/public health dual degree program, traveled to Cambodia to treat underserved children.

On Wednesday, the first class graduates from Columbia’s newly revamped dual degree program in dental medicine and public health. As a member of that first class, any student would have to work with flexibility and focus to chart a course in a program straddling two schools.

But as the only member of that first class, Tener Huang had a unique challenge—and opportunity—to be the student who not only tested out but helped shape a brand new program aimed to fill the need for dentists who address dental care and oral health from the perspective of population health.

When Tener first came to the College of Dental Medicine, she had no plans to pursue anything other than a traditional DDS degree.  She planned to finish in four years, complete a residency, then settle into private practice. But when she was in her third year, she was invited to an information session on the newly revamped DDS/MPH program, and the presentation made her change her course.

What was once a four-year program in dental medicine with public health courses squeezed into the evenings was newly reconfigured into a rigorous five-year program with two semesters devoted to public health. Huang had long had a commitment to service work—she volunteered both through her church and in college—and this program seemed to offer the ability to bring that focus to her dentistry career.

“Two weeks later I applied, two weeks later I interviewed, two weeks later I was admitted, and two weeks later I started at Mailman,” says Tener. “It was a whirlwind, and it was one of the best decisions I ever made.”

The program helped her envision her work as an extension of her dentist’s office. “I always wanted to do more for my patients than just see them one at a time and fix cavities,” says Tener. “There are just so many barriers to oral health and people who can’t access dentistry. Internationally, but even in our own backyards—in Washington Heights, there are children who can’t access oral health care.  In this program, I really saw what we could do to change that.”

Tener took every opportunity to explore ways to make an impact on public health and dentistry. She coordinated the dental program at Columbia’s Head Start, a federally funded child development program; made a visit to the Dominican Republic and two to to Cambodia to treat underserved populations; was a research assistant on three projects; was a teaching assistant; presented at a continuing medical education course; and also managed to lead a few student organizations. Allegedly, she also found time to sleep.

As the only student in the program, she knew she had exceptional opportunities offered to her. Her drive to take advantage of all of them impressed the faculty and set the bar high for future students.

“Tener not only fulfilled the requirements of the program but did so in such a way to establish the standard by which subsequent trainees are expected to perform,” says Burton L. Edelstein, a professor at the College of Dental Medicine who also heads its Section of Social and Behavioral Sciences and its Division of Behavioral Sciences.

Under Edelstein, who helped shape the oral health and dental care provisions in President Obama’s Affordable Care Act, she studied the lobbying process and how to influence dental policy change. When another professor, Sally Findley, started working on a book about community health workers and their impact on immigrant populations, Tener asked to do an independent study. Her drive impressed Findley, a professor of clinical population and family health and professor of clinical sociomedical sciences.  It also inspired other public health students.

“Tener probed into her own family background to find out about their immigrant experiences,” says Findley. “She was the lightning rod that got everyone else involved.”

Tener is excited to graduate from the program and start her residency in pediatric dentistry next year at the University of Medicine and Dentistry of New Jersey, a specialty she thinks dovetails well with public health policy. But the young woman who once pictured herself in private practice is not sure what she wants to do after her residency now that she sees so many opportunities on the horizon. She would like to continue working with community health workers possibly as a dental director, or go into academia, where her writing can help impact policy on oral health care. No matter what, she says, she will never see a patient without considering the larger community and global context.

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The results of the study will be presented at the American Thoracic Society (ATS) 2013 International Conference.

Asthma is characterized by bronchoconstriction, a tightening of the bronchial tubes that carry air into and out of the lungs. Bronchodilating medications called beta-agonists (β -agonists) are among the most common types of asthma medications and work by relaxing the airway smooth muscle (ASM) tissues. This study looked at whet her specific components of ginger could help enhance the relaxing effects of bronchodilators.

“Asthma has become more prevalent in recent years, but despite an improved understanding of what causes asthma and how it develops, during the past 40 years few new treatment agents have been approved for targeting asthma symptoms,” said lead author Elizabeth Townsend, PhD, post-doctoral research fellow in the Columbia University Department of Anesthesiology. “In our study, we demonstrated that purified component s of ginger can work synergistically with β – agonists to relax ASM.”

Read the full press release issued from the American Thoracic Society.

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viSNE reveals the progression of cancer in a sample of cells taken from a patient with acute myeloid leukemia. In figure a, the contours represent cell density in each region of the map. Each point represents a cell from the diagnosis sample (top, purple) or relapse sample (bottom, red). In figure b, cells from both diagnosis and relapse samples are shown in each map. Cells are colored according to intensity of expression of the indicated cell markers, enabling the comparison of expression patterns before and after relapse. For example, Fit3 is expressed primarily in the diagnosis sample, while CD34 emerges in the relapse sample. Image credit: Dana Pe’er, PhD/Columbia University

NEW YORK, NY (May 19, 2013) — In their quest to learn more about the variability of cells between and within tissues, biomedical scientists have devised tools capable of simultaneously measuring dozens of characteristics of individual cells. These technologies have led to new challenges, however, as scientists now struggle with how to make sense of the resulting trove of data. Now a solution may be at hand. Researchers at Columbia University and Stanford University have developed a computational method that enables scientists to visualize and interpret “high-dimensional” data produced by single-cell measurement technologies such as mass cytometry. The method, published today in the online edition of Nature Biotechnology, has particular relevance to cancer research and therapeutics.

Researchers now understand that cancer within an individual can harbor subpopulations of cells with different molecular characteristics. Groups of cells may behave differently from one another, including in how they respond to treatment. The ability to study single cells, as well as to identify and characterize subpopulations of cancerous cells within an individual, could lead to more precise methods of diagnosis and treatment.

“Our method not only will allow scientists to explore the heterogeneity of cancer cells and to characterize drug-resistant cancer cells, but also will allow physicians to track tumor progression, identify drug-resistant cancer cells, and detect minute quantities of cancer cells that increase the risk of relapse,” said co-senior author Dana Pe’er, PhD, associate professor of biological sciences and systems biology at Columbia. The other co-senior author is Garry P. Nolan, PhD, professor of microbiology & immunology at Stanford.

The method, called viSNE (visual interactive Stochastic Neighbor Embedding), is based on a sophisticated algorithm that translates high-dimensional data (e.g., a dataset that includes many different simultaneous measurements from single cells) into visual representations similar to two-dimensional “scatter plots”—the simple graphs with X and Y axes that many people first encounter in high school math and biology. “Basically, viSNE provides a way to visualize very high-dimensional data in two dimensions, while maintaining the most important organization and structure of the data,” said Dr. Pe’er. “Color is used as a third dimension to enable users to interactively visualize various features of the cells.”

The viSNE software can analyze measurements of dozens of molecular markers. In the two-dimensional maps that result, the distance between points represents the degree of similarity between single cells. The maps can reveal clearly defined groups of cells with distinct behaviors (e.g., drug resistance) even if they are only a tiny fraction of the total population. This should enable the design of ways to physically isolate and study these cell subpopulations in the laboratory.

Although the algorithm underlying the method is complex, Dr. Pe’er expects that all researchers, no matter their level of mathematical expertise, will be able to use viSNE.

To demonstrate the software’s utility, Dr. Pe’er and her colleagues used mass cytometry and viSNE to study bone marrow cells from patients with acute myeloid leukemia. Currently, clinicians can incorporate at most 4 to 8 markers to assess the cells. Because mass cytometry and viSNE can incorporate many more markers, viSNE is able to identify more subtle differences between cells. Using the algorithm, Dr. Pe’er and her colleagues were able to reveal previously unrecognized heterogeneity in the bone marrow cells they studied.

The researchers also showed that viSNE could detect minimal residual disease (MRD) — extremely small quantities of cancer cells that persist after chemotherapy and raise the risk of recurrence. “In blinded tests, we were able to find as few as 20 cancer cells out of tens of thousands of healthy cells,” said Dr. Pe’er. Such a small quantity of cells is extremely difficult to detect, even by the most experienced pathologist.

“The ability to detect MRD is critical for curing cancer,” added Dr. Pe’er. “Eliminating even 99.9 percent of a tumor doesn’t bring about a cure. You have to be able to find, and then eliminate, the tiny populations of cells that can survive therapy and lead to disease relapse.”

The paper is titled, “viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia.” The other authors are: El-ad David Amir (Columbia), Kara L. Davis (Stanford University), Michelle D. Tadmor (Columbia), Erin F. Simonds (Stanford), Jacob H. Levine (Columbia), Sean C. Bendall (Stanford), Daniel K. Shenfeld (Columbia), and Smita Krishnaswamy (Columbia).

The study was supported by grants from the National Science Foundation (MCB-1149728), National Institutes of Health Roadmap Initiative, the NIH Director’s New Innovator Award Program (1-DP2-OD002414-01), and the National Centers for Biomedical Computing (1U54CA121852-01A1).

The authors declare no financial or other conflicts of interest.

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