Four Pew Scholars in the Biomedical Sciences Receive 2009 National Institutes of Health Director's High-Risk Research Awards

Philadelphia, PA - Four Pew Scholars in the Biomedical Sciences have received grants totaling $7 million from the National Institutes of Health (NIH) to explore bold ideas that have the potential to catapult fields forward and speed the translation of research into improved health. Dr. Timothy E. Holy (a 2003 Pew Scholar) was awarded a $2.5 million Pioneer Award, designed to support individual scientists of exceptional creativity who propose pioneering—and possible transforming approaches—to major challenges in biomedical and behavioral research. Drs. Edward B. Brown III (a 2007 Pew Scholar), Kevin A. Janes (a 2009 Pew Scholar) and Leor S. Weinberger (a 2008 Pew Scholar) received $1.5 million New Innovator Awards, a “high risk” research award given to early-stage investigators whose projects have the potential for unusually high impacts.

Timothy E. Holy, Ph.D., is an associate professor of neurobiology at Washington University School of Medicine in St. Louis. He received a Ph.D. in physics from Princeton University in 1997. Dr. Holy develops new techniques for studying the nervous system and applies them to learn about neural processing and plasticity associated with the sense of smell. He is using the Pioneer Award to develop new optical imaging techniques to record the moment-by-moment activity of large numbers of neurons for hours at a time. These methods will allow neuroscientists to literally watch neuronal circuits compute, potentially changing our understanding of how the brain performs its functions.

Edward B. Brown III, Ph.D., received a doctorate in physics from Cornell University in 1999. He was a postdoctoral fellow at Massachusetts General Hospital from 1999 to 2002, when he was named an instructor. In 2005, Dr. Brown accepted a position as an assistant professor in biomedical engineering at the University of Rochester Medical Center. Dr. Brown hopes to develop novel imaging techniques that will reveal whether a cancer is likely to spread. Tumors, like all body tissues, are embedded in a dense mass of fibrous proteins and other molecules that support and nurture their growth and activity. Dr. Brown believes that the structure of this connective tissue, particularly the collagen fibers that hold it together, may reveal whether a tumor will metastasize. In previous work, he found that a drug called relaxin accelerates collagen turnover and also promotes tumor metastasis. This correlation suggests that collagen turnover might be linked to cancer's spread. Using imaging techniques he developed to monitor the structure of collagen fibers in the connective tissue of living animals, Dr. Brown hopes to create even better state-of-the-art imaging techniques to assess whether high collagen turnover is associated with an increased probability of metastasis in mice with growing breast tumors. His work could lead to novel, noninvasive methods for measuring a tumor's ability to metastasize, which could save patients from undergoing unnecessary chemotherapy for cancers unlikely to spread.

Kevin A. Janes, Ph.D., received a doctorate in bioengineering from the Massachusetts Institute of Technology in 2005. He completed his postdoctoral work at Harvard Medical School and then joined the faculty at the University of Virginia as an assistant professor in the Department of Biomedical Engineering. Dr. Janes' research focuses on the process of how cells take multiple signal inputs and interpret them to cause cell-fate decisions such as division, differentiation or death. Changes in cell fates, which can underlie complex diseases such as cancer, are usually the outcome of networks of signaling pathways that are interconnected. Instead of looking at a single pathway that directs cell fate changes, as is most commonly done, Dr. Janes uses a multipronged approach, combining quantitative biochemical techniques and statistical modeling. In addition, he performs experiments in cells that change more than one factor, or pathway, at a given time. By tracking changes in multiple signaling pathways during the transition of a cell into a new state, his studies contribute to the identification of optimal therapies for complex diseases like cancer that may require combinations of drug therapeutic approaches.

Leor S. Weinberger, Ph.D., received a doctorate in biophysics and computational biology from the University of California, Berkeley in 2004.  He pursued postdoctoral research at Princeton University from 2004 to 2007, then joined the faculty of the University of California, San Diego as an assistant professor of chemistry and biochemistry. Dr. Weinberger's long-term goal is to understand how genetic circuits work to suppress or enhance the development of cancerous cells. He believes that understanding the genetic circuits viruses use to infect human cells could be critical to understanding how cancer forms. After entering a host cell, many viruses become dormant. They switch off their genes and quietly wait for a signal telling them to multiply and infect more cells.  Upon receipt of that signal, viruses can rapidly ramp up production of the proteins that allow them to divide and conquer—in part because the genetic circuit that controls this behavioral “switch” from dormant to active responds to “positive feedback.” In a positive feedback circuit, the key regulatory molecule stimulates production of more of itself, so once the switch is thrown, the response rapidly snowballs and viral replication kicks into high gear. Unfortunately, these circuits tend to be leaky. The challenge for a dormant virus then becomes how to distinguish between a true “launch” signal and the sort of errant “noise” that is inherent in the system. Combining cutting-edge techniques in molecular biology and microscopy with mathematical models for predicting the behavior of molecules in single cells, Dr. Weinberger will explore how the HIV and CMV viruses regulate the circuits that allow them to decide between dormancy and replication. His work already has led to the identification of a novel therapeutic strategy for keeping HIV in check, and these further studies could lead to insights about how cells resist—or succumb to—becoming cancerous.

About the Pew Scholars Program

The Pew Scholars program identifies and invests in young investigators of outstanding promise in science relevant to the advancement of human health. The program provides crucial support that enables scientists to take calculated risks and follow unanticipated leads to maximize the benefits of their research for society. Scholars also gain inclusion into a select community of scientists that includes three Nobel Prize winners, MacArthur Fellows and recipients of the Albert Lasker Medical Research Award. Now in its 25th year, the program has invested more than $125 million to fund over 460 scholars. For additional information on the Pew Scholars Program in the Biomedical Sciences, please visit www.pewscholars.org.

For more information about the NIH High Risk Research Awards, please visit http://nihroadmap.nih.gov/newinnovator/