Members include experts in the scientific, engineering, and health professional fields, all of whom volunteer their time to provide reports that have significantly improved the welfare of citizens worldwide.

Staudt is just one of the 84 new members who were nominated by peers, in recognition of their notable and ongoing achievements in original research. All newly appointed members will be officially inducted into the NAS during an April 2014 ceremony.

Staudt is known as a pioneer of gene expression profiling His laboratory currently studies the molecular basis of human lymphoid malignancies through the use of functional genomics, chemical genetics and molecular biological techniques. His groundbreaking developments in cancer research and genomics include the discovery of previously unknown types of diffuse large B cell lymphoma, the use of gene expression profiling to identify distinct cancer subgroups, the prediction of cancer patient survival with the use of gene expression signatures, and the discovery of new therapeutic targets in molecularly-defined subtypes of cancer using loss-of-function RNA interference (RNAi) genetic screens.

“This nomination is very gratifying because it validates some of the ideas about lymphoma diagnosis and treatment that we have been trying to promote over the past decade,” Staudt said.  “It establishes that we are on a path of making progress for patients. Also, it is a true testament to the strong support given to our lab by the NCI and especially to the outstanding post docs, students, and technicians working in the lab over the past 25 years.”

In this video from March 2012, Staudt discusses the basic biology of targeted therapy for Diffuse B-cell Lymphoma and about ibrutinib, a drug with a high degree of efficacy—and only modest side effects—in the treatment of the ABC form of Diffuse B-cell Lymphoma.

Click here to view the embedded video.

Scott McNeil, director of the Nanotechnology Characterization Lab at the Frederick National Laboratory for Cancer Research

The protein tumor necrosis factor-alpha (TNF-alpha) is a powerful weapon in the arsenal to control cancer. Unfortunately, as is the case with many potent cancer therapies, the use of TNF-alpha as an anti-cancer therapy has been severely limited. “It was so toxic that it caused death,” and researchers gave up on it, explains Scott McNeil, director of the Nanotechnology Characterization Lab at the Frederick National Laboratory for Cancer Research.

That was back in the 1990s. Today, TNF-alpha is a prime example of how to safely and effectively deliver toxic substances to cancer cells through the use of nanotechnology.

McNeil’s lab, part of the federally funded research and development center operated by SAIC-Frederick for the National Cancer Institute, worked with a drug company to reformulate TNF-alpha by coupling it with gold nanoparticles. Using the nanotechnology-enhanced protein, it appears possible to safely inject up to three times the amount that had been lethal with previous versions. The modified drug has been through a Phase 1 clinical trial and is entering Phase 2.

In McNeil’s lab, and for other scientists using nanotechnology for drug delivery, stories like this one are increasingly common. Researchers are looking to accelerate the development of potential nanotechnology drugs for cancer by exploring ways to reduce side effects and make treatments hit their targets more effectively. This can mean using nanotechnology to reformulate drugs that may have failed in previous clinical trials. In some cases, by attaching a nanoparticle to an existing drug, researchers may not only be able to lower its toxicity, but they may also see significant life expectancy gains for patients.

Many cancer drugs are approved based on how long they delay the progression of disease. Some drugs on the market “only improve life expectancy by maybe five weeks,” says McNeil. He sees nanomedicine as a potential game-changer for cancer drugs in the future.

McNeil, both a chemist and biologist, has spent the majority of his career working in nanotechnology, but when he was asked to apply his expertise to find better drugs for cancer, he was skeptical. “My professional career was mostly military,” says the former Army officer. “I was using nanotech for military applications at SAIC, using quantum dots to see if you scatter things, where they land. I got a call out of the blue in December of 2003 and the message was, ‘We want to use nanotech for cancer applications.’ I thought, ‘What are they thinking? You are going to put a cadmium quantum dot in a human? There is no way!’ I discounted it at first and I actually ignored the emails, hoping it would go away.”

But it did not go away.  In fact, much has changed in the last 10 years. Now, nanopharmaceuticals are beginning to demonstrate their capacity to place the drugs directly in the tumor, where they will do the most good, rather than let them roam freely in the body. A drug is attached to a nanoparticle, which is often a tiny little sphere. To put it in perspective, a nanometer is one billionth of a meter; the width of a single strand of hair is about 10,000 nanometers. The nanoparticle is small enough to flow through blood vessels and into a tumor, where the particle dissociates, and the drug is released. In the end, the goal of nanomedicine is that the only part of the body affected by the drug is the tumor, the area of need.

McNeil’s Nanotechnology Characterization Lab was founded in 2004 in collaboration with the Food and Drug Administration and the National Institute of Standards and Technology. There is one thing the lab does not do: develop nanotechnology drugs. Instead, researchers there—ranging in expertise from cancer biology and toxicology to chemistry, immunology, and physics—help investigators from around the world create the best drugs possible. “We help investigators get from proof of concept, where they are generating a few tens of milligrams of material and get into clinical trials, where they are going to need kilograms of materials,” say McNeil. “That translational research, as we call it, is absolutely germane to getting into clinical trials.”

The majority of scientists who apply for assistance from the NCL are seeking FDA approval for their nanotech drugs but they don’t have the resources to optimize their formula. The NCL can help. “We help them understand what is involved with their particle because they don’t have the tools that we have to be able to characterize,” says McNeil. “They may have a nice picture or cartoon of it but until they see our electron micrographs, they don’t know what it looks like.”

The Nanotechnology Characterization Lab serves two purposes. After a molecule has been through the NCL’s assay cascade which consists of a set of tests that evaluate the preclinical toxicology, pharmacology, and efficacy of nanoparticles, the NCL is able to offer an evaluation. “The investigator is going to need $40 million dollars to get into Phase 2 trials. Investigators need to justify the investment. We help them generate data they need to further their work and then we serve as a third-party evaluation.” That is crucial, McNeil says, for an investigator seeking funding. “A venture capital company can come to us and say, ‘Well, what do you really think of this? Let’s see your data, and explain it and defend it.’ We, obviously, cannot endorse it but we can discuss the data in the context of what they are trying to do. That really holds a lot of weight.”

Consider the example of Abraxane (paclitaxel), which was approved for use by the FDA in 2005. Abraxane, a variably toxic but widely prescribed cancer drug, has been enhanced by attaching it to a nanoparticle, thereby creating a new, targeted treatment. “Because of the size and the binding to a different receptor, that drug now has decreased toxicity compared to the former drug. For the nanoparticle-Abraxane conjugate toxicity is very marginal, at least for immunotoxicity and hypersensitivity,” says McNeil.

Since 2005, the Nanotechnology Characterization Lab has characterized nearly 300 different particles. Six of them are in clinical trials. “Depending upon what community you are from, either that is a terrific ratio or that is a poor ratio,” explains McNeil. “We view it as a super terrific ratio. A pharmaceutical company can make hundreds of thousands of different drugs and only about one out of 100,000 gets into clinical trials.”

Nanotechnology’s place in the cancer treatment arsenal also appears secure. A new report from Infiniti Research Limited, a marketing research firm specializing in pharmaceuticals and health care, forecasts that the nanotechnology drug delivery market is on track to double within the next five years.

For more information about NCL, visit: http://ncl.cancer.gov/.

Anuradha Budhu, Ph.D.

Anuradha Budhu, Ph.D., heads a research team at the National Cancer Institute that recently  uncovered an imbalance between saturated and unsaturated fats (such as palmitic or fatty acids) that occur in patients with a common liver cancer called hepatocellular carcinoma, or HCC. Budhu’s team also determined that HCC patients with high unsaturated fat levels had poor survival rates, suggesting that a shift of balance toward saturated fats may be a novel therapeutic strategy in the treatment of aggressive liver cancer.

Budhu, who earned her doctorate at Cornell University, is a staff scientist at NCI’s Center for Cancer Research. She has been awarded CCR’s outstanding postdoctoral award as well as the NCI Director’s Innovation Award.

She has been in the Laboratory of Human Carcinogenesis since 2002 working to uncover molecular and genomic targets associated with liver cancer and its metastasis. Using these techniques in a unique way, she and her colleagues were able to link fatty acids with HCC patient outcome.

Past studies on HCC focused on the roles of either genes or metabolites, which are byproducts of metabolism such as fatty acids. Budhu’s group was the first to interweave these two distinct platforms to search for the key molecular drivers of HCC. As a result, they uncovered a set of cellular alterations in fat signaling pathways associated with HCC and discovered that an important transmitter of fatty acid flow—a gene called stearoyl CoA-desaturase, or SCD, that contributed to unfavorable outcomes for HCC patients. The study findings were published in Gastroenterology.

To profile metabolite and gene signals in HCC, Budhu and her colleagues worked with tissue samples taken from 386 HCC clinical patients that they divided into three sets—training, test and validation. Using the training set, they profiled paired tumor and non-tumor samples to identify the interdependent metabolites and genes in a HCC subtype that is most often associated with poor patient survival.

Once these molecular targets were identified, they searched for key pathways that connected these metabolites and genes, which they then confirmed in test and validation tissue sample sets for accuracy. As a result, they found that SCD and its associated metabolite—unsaturated fat—were associated with aggressive HCC outcomes. While these integrative results have shown that SCD and its related metabolites may one day be valuable as biomarkers and prognostic indicators for HCC, more work is needed to determine the mechanism underlying SCD’s role in HCC, said Budhu.

The 11 recipients will each receive $3 million for their outstanding work in the field of science; eight of them have received NCI grants to further their research:

• David Botstein Ph.D., director of the Lewis-Sigler Institute for Integrative Genomics and the Anthony B. Evnin professor of genomics at Princeton University, was recognized for linkage mapping of Mendelian disease in humans using variations in a DNA sequence.

• Lewis C. Cantley, Ph.D., director of the Cancer Center at Weill Cornell Medical College and New York-Presbyterian Hospital, was awarded for his discovery of PI 3-Kinase and its role in cancer metabolism. His research discovered that human cancers frequently have mutations in PI3K and he has worked to identify new treatments for cancers that result from defects in this pathway.

• Titia de Lange Ph.D., head of the Laboratory of Cell Biology and Genetics, and director of the Anderson Center for Cancer Research at the Rockefeller University, was awarded for her research on telomeres, illuminating how they protect chromosome ends and their role in genome instability in cancer. De Lange identified a protein complex within telomeres, called shelterin, and has shown how this complex hides the chromosome end from cellular machinery that detects and repairs broken DNA tips.

• Napoleone Ferrara, M.D., distinguished professor of pathology and senior deputy director for basic sciences at Moores Cancer Center at the University of California, San Diego, was awarded for his discoveries in the mechanisms of angiogenesis that led to therapies for cancer and eye diseases.  Ferrara’s research has helped identifying the role of the human VEGF gene in promoting angiogenesis—the formation of new blood vessels that can feed tumor growth—and subsequent development of two major drugs: bevacizumab (Avastin) which is used to treat multiple forms of cancer and ranibizumab (Lucentis), which treats age-related macular degeneration, a leading cause of blindness in the elderly.

• Eric Lander, Ph.D., founding director and core member of the Broad Institute of MIT and Harvard, was awarded for the discovery of general principles for identifying human disease genes, and enabling their application to medicine through the creation and analysis of genetic, physical and sequence maps of the human genome. Lander was one of the leaders of the Human Genome Project.

• Charles L. Sawyers, M.D., chair of the Human Oncology and Pathogenesis Program at Memorial Sloan-Kettering Cancer Center, was awarded for his work in cancer genes and targeted therapy.  Sawyers research focuses on cancer drug resistance, which led him to the discovery of the drug enzalutamide (Xtandi), used for advanced prostate cancer.

• Bert Vogelstein, M.D., co-director of the Ludwig Center at Johns Hopkins and a Howard Hughes Medical Institute investigator, was awarded for his work in cancer genomics and tumor suppressor genes. Vogelstein’s identification of p53 gene mutations in colon cancer was groundbreaking and resulted in further research linking this gene mutation to other cancers. It is now known as the most common gene mutation in all cancers.

• Robert A. Weinberg, Ph.D., professor for cancer research at MIT and director of the MIT/Ludwig Center for Molecular Oncology, was awarded for his characterization of human cancer genes. Weinberg is known for his discoveries of the first human oncogene—a gene that causes normal cells to form tumors—and the first tumor suppressor gene.

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Arnold Rabson, M.D., left, accepts the Special Recognition Award from AACI, on behalf of his father. Presenting the award at the Oct. 15 ceremony is AACI President William S. Dalton, M.D., Ph.D., chief executive officer and director of the Moffitt Cancer Center. Photo by Mike Gatty.

His son, Arnold Rabson, M.D., accepted the award on his behalf.

In addition to his tenure at NCI, the senior Rabson is also a member of the Institute of Medicine and a fellow of the American Association for the Advancement of Science. He has held clinical professorships in pathology at Georgetown University Medical Center and George Washington University, and at the Uniformed Services University of the Health Sciences.

The Association of American Cancer Institutes comprises 95 leading cancer research centers in the United States. The award was presented to during the 2012 AACI and Cancer Center Administrators Forum Annual Meeting.

In separate experiments, the team sought to determine if the presence or absence of commensals in the gut played a role in skin immunity. They observed that adding or eliminating beneficial bacteria in the gut did not affect the immune response at the skin. These findings indicate that microbiota found in different tissues—skin, gut, lung—have unique roles at each site and that maintaining good health requires the presence of several different sets of commensal communities. This study provides new insights into the protective role of skin commensals and demonstrates that skin health relies on the interaction of commensals and immune cells.

The study was led by investigators in the laboratories of Yasmine Belkaid, Ph.D., at the National Institute of Allergy and Infectious Diseases, in collaboration with Julie Segre, Ph.D., at the National Human Genome Research Institute, and Giorgio Trinchieri, M.D., and Kong at the National Cancer Institute.

Understanding the Good Bacteria in Our Skin:

Click here to view the embedded video.

Click here to view the embedded video.

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Orentas receiving research grant award at Hyundai Hope On Wheels ceremony

Hyundai Hope On Wheels handprint ceremony

Rimas Orentas, Ph.D., from NCI’s Pediatric Oncology Branch in the Center for Cancer Research, is one of the 2012 recipients of a $250,000 research grant from Hyundai Hope On Wheels. This grant, given in honor of National Childhood Cancer Awareness Month, will allow Orentas to focus on new therapeutics for immunotherapy of pediatric tumors. Dr. Orentas’ current research focuses on the engineering of T lymphocytes for the immunotherapy of cancer in both mouse and human systems.

Orentas received his award at a Hyundai Hope On Wheels handprint ceremony where young cancer patients placed their paint-coated, colorful handprints on his lab coat.

Hyundai Hope On Wheels involves more than 800 dealers across the U.S. to raise awareness for childhood cancer.  The nonprofit has committed close to $57 million to childhood cancer research since its inception in 1998.

Steven A. Rosenberg, M.D., Ph.D.

Steven A. Rosenberg, M.D., Ph.D., a pioneer in the fields of basic tumor immunology and cancer immunotherapy, can add recipient of the 17th annual Keio Medical Science Prize to his list of academic and professional honors.

The prize, awarded by Keio University in Tokyo, recognizes the outstanding and creative achievements of researchers in the fields of medicine and life sciences, in particular those contributing to scientific developments in medicine. Six recipients of the Keio Medical Science Prize have later won the Nobel Prize.

Rosenberg, chief of surgery at the National Cancer Institute and head of the Tumor Immunology Section in NCI’s Center for Cancer Research, has been at the forefront of efforts to develop an effective immunotherapy for human cancer. In his recent work, he has used genetic engineering to develop anti-tumor immune lymphocytes.

“I am deeply grateful to the selection committee for awarding me the very prestigious Keio Medical Science Prize,” Rosenberg said. “This award recognizes our efforts to develop new immunotherapies for patients with cancer. It is a great honor to be able to work to develop new treatments for patients with this devastating disease.”