Twenty of America’s Most Promising Scientists Selected as 2008 Pew Scholars in the Biomedical Sciences

Contact: Kip Patrick, 202.552.2135

Washington, DC - 06/12/2008 - The Pew Charitable Trusts and the University of California at San Francisco (UCSF) announced today that 20 exceptional researchers have been selected as 2008 Pew Scholars in the Biomedical Sciences. Scholars receive a $240,000 award over four years to help support their research, as well as gain inclusion into a unique community of scientists that encourages collaboration and exchange of ideas. The program is funded by Pew through a grant to UCSF.

“Pew’s Program in the Biomedical Sciences is designed to enable scientists to take calculated risks, expand their research and follow unanticipated leads,” said Rebecca W. Rimel, President and Chief Executive Officer of The Pew Charitable Trusts. “Pew is honored to invest in these brilliant minds, and to provide financial and professional support as they pursue their pioneering breakthroughs.”

Launched in 1985, The Pew Scholars Program in the Biomedical Sciences supports early to midcareer scientists and has invested more than $100 million to fund over 400 scholars.

The Pew Scholars selection process is rigorously competitive, as all applicants are highly talented researchers in their fields. Applicants must be nominated by an invited institution and must demonstrate excellence and innovation in their research. This year, 149 institutions were invited to nominate a candidate in basic biomedical research, and 117 eligible nominations were received. The scholars are selected by a distinguished national advisory committee, chaired by Dr. Torsten N. Wiesel, president emeritus of Rockefeller University and a 1981 Nobel laureate.

Related Press Release: Ten Latin American Scientists Named 2008 Pew Fellows in the Biomedical Sciences 

The 2008 Pew Scholars in the Biomedical Sciences are:
Gilad Barnea, Ph.D.Brown University
Laurie A. Boyer, Ph.D.Massachusetts Institute of Technology
Antonio J. Giraldez, Ph.D.Yale University
Aaron D. Gitler, Ph.D.University of Pennsylvania
Felicia D. Goodrum, Ph.D.University of Arizona
Richard I. Gregory, Ph.D.Children’s Hospital, Boston
Jianping Jin, Ph.D.University of Texas Health Science Center, Houston
Anatol C. Kreitzer, Ph.D.University of California, San Francisco
Deborah J. Lenschow, M.D., Ph.D.Washington University in St. Louis
Ian J. MacRae, Ph.D.Scripps Research Institute
Bryce Nickels, Ph.D.Rutgers University
Susannah Rankin, Ph.D.Oklahoma Medical Research Foundation
John F. Rawls, Ph.D.University of North Carolina, Chapel Hill
Seth M. Rubin, Ph.D.University of California, Santa Cruz
Holger Sondermann, Ph.D.Cornell University
Michael A. Sutton, Ph.D.University of Michigan
Benjamin R. tenOever, Ph.D.Mount Sinai School of Medicine
Leor S. Weinberger, Ph.D.University of California, San Diego
Julia Zeitlinger, Ph.D.Stowers Institute for Medical Research
Hui Zong, Ph.D.University of Oregon

Gilad Barnea, Ph.D.Gilad Barnea, Ph.D., received a doctorate in pharmacology from New York University in 1996.  He then went to Columbia University, where he undertook postdoctoral studies from 1996 to 2001, after which he joined the staff as an associate research scientist.  In 2007, Dr. Barnea became an assistant professor of neuroscience at Brown University.  Dr. Barnea plans to map out the neural circuits that power the mouse’s sense of smell.  When odor molecules enter the nose, they bind to special olfactory receptors present on sensory cells that line the nasal cavity.  Each sensory cell produces only one of a possible thousand or so olfactory receptors, and every receptor corresponds to only a specific set of scent molecules.  Thus, for every smell, a distinct set of sensory cells that recognize that particular odor transmits the information to the olfactory bulb, which then relays the signal to the brain areas that handle olfactory information.  How the brain decodes that information is not known, but Dr. Barnea believes that a first step toward understanding the process involves learning exactly how all these nerve cells are wired together.  As a postdoctoral fellow, Dr. Barnea developed a novel method for labeling neurons in mice so that nerve cells on the receiving end of a neuronal signal can be identified.  Using this unique system, Dr. Barnea now will investigate how olfactory information passes from the nose to the brain.  His results could lead to a deeper understanding of how organisms recognize specific odors that then trigger behavioral responses (for example, recognizing a smell as the kind of smoke necessitating a flight response).

Laurie A. Boyer, Ph.D.Laurie A. Boyer, Ph.D., received a doctorate in biochemistry from the University of Massachusetts Medical School in 2000.  She continued there as a postdoctoral fellow for five months before completing her postdoctoral studies at the Whitehead Institute for Biomedical Research.  In 2005, Dr. Boyer joined the staff at Whitehead as a scientist, and in 2007, she accepted a position as an assistant professor of biology at the Massachusetts Institute of Technology.  Dr. Boyer will investigate how embryonic stem cells execute the diverse genetic programs that allow them to give rise to every type of tissue in the body.  For these versatile cells to be able to form hearts, livers, bones or brains, they must be able to switch on the genes specific for those cell types while simultaneously shutting down all the genes for the cell types needed for other organs.  Using an array of genetic, biochemical and cell biological tools, Dr. Boyer hopes to dissect the mechanisms that allow cells to reprogram their genomes and lock in their identities.  In particular, she will explore how a class of proteins called the polycomb group help to reign in the potential of embryonic stem cells as they differentiate into various tissue types by altering their chromosome structure.  Her work could affect the development and application of stem cell therapeutics and could shed light on how disruption of important cellular developmental processes can lead to a variety of diseases, including cancer.

Antonio J. Giraldez, Ph.D.Antonio J. Giraldez, Ph.D., received a doctorate in developmental biology and genetics from the European Molecular Biology Laboratory in Germany in 2002.  He completed his postdoctoral training in the United States, first at the New York University School of Medicine from 2003 to 2005 and then at Harvard University.  In 2006, Dr. Giraldez accepted a position as an assistant professor of genetics at Yale University School of Medicine.  Dr. Giraldez will investigate how microRNAs (miRNAs) regulate gene activity during development and in disease.  Nearly five percent of human genes are likely to encode miRNAs—small RNA molecules that serve as widespread regulators of gene activity.  But little is known about which genes—and hence which physiological processes—these miRNAs influence.  As a postdoctoral fellow, Dr. Giraldez generated zebrafish that do not produce any miRNAs.  By comparing these mutants to normal zebrafish, he identified more than 200 genes whose activity is controlled by these small RNAs, and has discovered one miRNA in particular that plays a major role in early development and brain formation.  Using advanced cutting-edge techniques in molecular, computational and developmental biology, Dr. Giraldez will expand his search for novel miRNAs and their gene targets and try to determine how their interaction influences development, particularly of the nervous system.  Because disturbances in miRNA biology have been implicated in human developmental disorders and cancers, his work ultimately could yield insights relevant to the treatment of human disease.

Aaron D. Gitler, Ph.D.Aaron D. Gitler, Ph.D., received a doctorate in cell and molecular biology from the University of Pennsylvania School of Medicine in 2004.  He continued his postdoctoral training at the Whitehead Institute for Biomedical Research, and in 2007 returned to the University of Pennsylvania as an assistant professor of cell and developmental biology.  Dr. Gitler plans to investigate how protein misfolding can lead to neurodegenerative disorders such as Parkinson’s disease.  When proteins are synthesized, they emerge as long, string-like molecules that then need to fold up into their proper three-dimensional shapes.  When they fold incorrectly, proteins form aggregates that can kill cells—a situation that can lead to neurodegenerative diseases such as Alzheimer’s and Parkinson’s.  In groundbreaking work accomplished during his postdoctoral fellowship, Dr. Gitler generated yeast cells that produce α-synuclein, a protein found in the brains of people with Parkinson’s disease.  Using these engineered yeast cells, he identified a set of genes that prevented the α-synuclein from generating toxic effects. These genes not only allowed the yeast cells to survive, but also were able to stave off toxicity when introduced into mice with a Parkinson’s-like disease.  Dr. Gitler now will explore how α-synuclein contributes to neurodegeneration—and how the genes he discovered in yeast rescue cells from death.  He also will use his yeast system to study the molecular pathways involved in other neurodegenerative disorders, such as Alzheimer’s disease.  His work could open up new avenues for the treatment of many devastating neurological disorders.

Felicia D. Goodrum, Ph.D.Felicia D. Goodrum, Ph.D., received a doctorate in molecular genetics from Wake Forest University Medical School in 1998.  She remained at Wake Forest as a postdoctoral fellow until 1999, when she moved to Princeton University to continue her postdoctoral training.  In 2006, she was appointed an assistant professor of immunobiology, molecular and cellular biology at the University of Arizona.  Dr. Goodrum will explore how herpes viruses can establish infections that can last a lifetime.  The human cytomegalovirus (HCMV)—a herpes virus that infects an estimated 60 to 99 percent of the world’s population—is particularly insidious because it can take up residence inside specialized cells that give rise to our blood and immune cells.  There the virus can sit latent until reawakened in immune-compromised individuals, such as those with AIDS or undergoing chemotherapy. During her postdoctoral studies, Dr. Goodrum developed a novel method for coaxing HCMV to establish a latent infection in cultured cells, and she used this system to identify a viral gene that allows HCMV to hide.  Dr. Goodrum has begun to develop mice in which the type of cells that can harbor HCMV—called human hematopoietic progenitor cells—can thrive.  She now will introduce into the mice human hematopoietic progenitor cells that she has already infected with HCMV so that she can study the molecular mechanisms that allow the virus to interact with host cells and establish latent infection.  Her work could provide new avenues for the development of vaccines and anti-viral medications.

Richard I. Gregory, Ph.D.Richard I. Gregory, Ph.D., received a doctorate in genetics from the University of Cambridge in 2001.  He undertook postdoctoral studies at the Fox Chase Cancer Center from 2001 to 2003 and at the Wistar Institute from 2003 to 2006.  He then accepted a position as an assistant professor in biological chemistry and molecular pharmacology at the Children’s Hospital, Boston and Harvard Medical School, where he also is a member of the Harvard Stem Cell Institute.  Dr. Gregory will investigate the role that microRNAs (miRNAs) play in development and cancer.  These small RNAs regulate the activity of many genes and clearly are important for normal development, as animals lacking miRNAs die as early embryos.  Incorrect miRNA processing also has been implicated in the development of cancer.  Initially, miRNAs are synthesized as larger precursors, which are then sliced by several enzymes to form a mature miRNA.  In cancer cells, the precursor miRNAs are produced, but they do not get processed into their mature form.  Interestingly, a similar buildup of precursor miRNAs also occurs in embryonic stem cells, a situation that may help them maintain their potential to develop into any type of tissue in the body.  Once the stem cell decides which type of tissue to produce, the miRNA stockpile can rapidly be converted into mature miRNAs that help launch the appropriate developmental program.  Dr. Gregory has isolated a protein, called Lin-28 that appears to block miRNA processing to maturity in embryonic carcinoma cells.  Now, using advanced genetic and molecular biological techniques, Dr. Gregory hopes to discover exactly how Lin-28 inhibits miRNA processing and determine whether the protein actually promotes cancer formation—and whether it can preserve stem cells in their embryonic, full-potential state.  His work could reveal a new mechanism by which cells can become cancerous, and could provide a new means for maximizing the potential of stem cells—both of which have therapeutic ramifications for the treatment of human disease.

Jianping Jin, Ph.D.Jianping Jin, Ph.D., received a doctorate in biochemistry from Texas A&M University in 2000.  He undertook postdoctoral studies at the Baylor College of Medicine and Harvard Medical School from 2001 to 2007, then returned to Texas as an assistant professor of biochemistry and molecular biology at the University of Texas Health Science Center at Houston.  Dr. Jin will explore the molecular assembly line that cells use to mark unwanted proteins for disposal.  When proteins are either damaged or no longer useful, cells remove them from circulation, because  allowing them to pile up can be toxic to the cell and even lead to cancer and neurodegenerative diseases such as Alzheimer’s.  To mark proteins for destruction, cells rely on a tag-team of three enzymes, dubbed E1, E2 and E3.  While cells are known to possess dozens of different E2-type enzymes and hundreds of different E3s, it was believed for the last 25 years that they only have a single E1.  However, in previous work, Dr. Jin discovered a second E1 enzyme which he called Uba6.  Using a multitude of cutting-edge methods in biochemistry and cell and molecular biology, Dr. Jin now hopes to fully characterize this newly discovered protein, including determining which E2s and E3s form part of its team and exploring its biological role.  Although scientists now know that Uba6 is essential for mouse development, it is unclear what specifically it does.  In addition to enhancing understanding of basic cell maintenance, Dr. Jin’s findings could lead to the development of new therapies for disorders that arise from an unhealthy accumulation of cellular trash.

Anatol C. Kreitzer, Ph.D.Anatol C. Kreitzer, Ph.D., received a doctorate in neurobiology from Harvard University in 2001.  After a two-year postdoctoral fellowship at Harvard, Dr. Kreitzer continued his training at Stanford University.  In 2007, he accepted a position as an assistant professor of physiology and neurology at the University of California, San Francisco.  Dr. Kreitzer wants to characterize the neural circuits that control movements—circuits that, when disrupted, lead to disorders such as Parkinson’s and Huntington’s diseases.  Deep within the brain, a cluster of structures called the basal ganglia direct movement on a moment-to-moment basis; ultimately, however, the activity of the basal ganglia is influenced by “higher thinking” brain regions, such as the motor cortex.  These conscious controls are filtered through a region called the striatum, which integrates input from different brain areas before passing the instructions along to the basal ganglia.  Little is known about how different neurons and neuronal circuits in the striatum control motor activity.  As a postdoctoral fellow, Dr. Kreitzer used advanced techniques for monitoring neural activity to uncover a key difference between two neuronal pathways that emerge from the striatum.  This discovery led him to a novel treatment that repaired motor problems in mice with Parkinson’s disease. Now, using cutting-edge techniques in genetics and molecular biology, Dr. Kreitzer will manipulate and observe the activities of these distinct neuronal pathways and try to determine how they regulate motor behaviors in mice—work that could lead to the development of novel treatments for movement disorders in humans such as Parkinson’s and Huntington’s diseases.

Deborah J. Lenschow, M.D., Ph.D.Deborah J. Lenschow, M.D., Ph.D., received a doctorate in immunology from the University of Chicago in 1995 and a medical degree from the same institution in 1998.  She completed her internship, residency and clinical training at the Barnes-Jewish Hospital in St. Louis in 2001.  She then engaged in postdoctoral studies at Washington University from 2001 to 2006 before joining the faculty there as an assistant professor of medicine.  Dr. Lenschow wants to unravel the molecular chain of events that allows the immune system to resist viral infection.  Combating viral infection is a complicated biological process that is coordinated, in part, by molecules called interferons.  Interferons work by switching on hundreds of genes—called interferon-stimulated genes (ISGs)—known to be important to the development of an immune response.  During her postdoctoral fellowship, Dr. Lenschow isolated many ISGs and found that one in particular, ISG15, encodes a critical antiviral molecule.  Using mice engineered to lack ISG15, she further found that infecting the mice with influenza or herpes viruses often proved fatal.  Using state-of-the-art techniques in genetics, protein chemistry and cell and molecular biology, Dr. Lenschow now will examine how ISG15 exerts its antiviral effects.  In particular, she wants to learn what form of the protein is most effective, and then search for a receptor protein that recognizes ISG15 and mediates its activity.  As a physician-scientist, Dr. Lenschow already has seen her graduate research translate into a novel therapeutic for rheumatoid arthritis.  Her current studies of this newly discovered antiviral molecule could provide similarly novel treatment strategies for preventing or battling viral infections.

Ian J. MacRae, Ph.D.Ian J. MacRae, Ph.D., received a doctorate in biochemistry and molecular biology from the University of California, Davis in 2002.  He conducted postdoctoral studies at the University of California, Berkeley before joining the staff at the Scripps Research Institute as an assistant professor of molecular biology in 2007.  Dr. MacRae will probe the molecular mechanisms that allow small RNA molecules to regulate the activity of a broad range of genes.  Scientists recently have come to recognize the importance that small RNAs play in controlling the activities of genes involved in a wide variety of biological processes, including stem cell division, development, learning and memory.  These so-called microRNAs operate by binding to a large protein complex called a RISC, which then uses its bound RNA as a guide to direct it to the genes it will shut off.  During his postdoctoral fellowship, Dr. MacRae determined the three-dimensional structure of an enzyme called Dicer that prepares microRNAs to be loaded onto a RISC.  Now, using advanced biochemical, microscopic and crystallographic techniques, Dr. MacRae aims to clarify how Dicer and other accessory proteins deliver the RNAs to the RISC, a step that effectively programs the complex to attack its target gene.  He also will explore how proteins he engineered to be defective in their ability to load these RNAs affect the activity of the complex.  His findings could yield important insights into the function of microRNAs that might provide scientists with better tools for controlling gene activity in experimental systems or could even one day be used therapeutically.

Bryce E. Nickels, Ph.D.Bryce E. Nickels, Ph.D., received a doctorate in microbiology and molecular genetics from Harvard University in 2002.  He remained at Harvard as a postdoctoral fellow until 2007, when he joined the faculty at Rutgers University as an assistant professor in genetics and a member of the Waksman Institute of Microbiology.  If awarded a grant, Dr. Nickels will explore whether aborted RNA transcripts might regulate gene activity.  The first step in gene activation involves copying the information contained in a DNA molecule into a piece of RNA.  That process—called transcription—is carried out by a protein called RNA polymerase (RNAP).  When RNAP transcribes a gene in a test tube, it sometimes repeatedly starts and stalls before it finally moves smoothly along the DNA to produce a full-length transcript.  This “stuttering” behavior generates tiny pieces of what is termed “abortive” RNA—some only two nucleotides in length.  These abortive RNAs have so far only been detected in the test tube; no one yet knows whether RNAPs generate similar products inside an actual cell.  Using advanced techniques in genetics and cell and molecular biology, Dr. Nickels hopes to determine whether abortive RNAs are produced in bacterial cells, and, if so, whether these tiny RNA fragments play a role in regulating gene activity.  His findings could lead to the discovery of an exciting but previously unrecognized class of regulatory RNAs, and could also suggest novel strategies for treating or controlling microbial infections.

Susannah Rankin, Ph.D.Susannah Rankin, Ph.D., received a doctorate in molecular microbiology from Tufts University School of Medicine in 1995.  She pursued postdoctoral studies at Harvard Medical School from 1995 to 2006, then joined the staff of the Oklahoma Medical Research Foundation as an assistant member in the department of molecular, cell and developmental biology.  Dr. Rankin wants to understand the intricate molecular mechanisms that govern how dividing cells parcel out chromosomes to their daughters.  Before cells reproduce, they duplicate their DNA.  These chromosome copies remain attached to the originals until they are ready to be pulled apart—with a copy of each chromosome going to each of the daughter cells.  This cohesion of chromosome copies prior to separation is crucial: defects in the proteins that hold these sister chromosomes together can lead to developmental disorders and possibly cancer.  During her postdoctoral fellowship, Dr. Rankin identified a new protein, called sororin, that regulates sister chromosome cohesion.  Now, using a combination of genetic, biochemical and cell biological techniques, Dr. Rankin will try to determine when, where and how sororin helps hold chromosomes together, and she will explore how defects in other cohesion-related proteins derail the process.  Her findings could provide a sharper view of the molecular dance that directs proper chromosome segregation, and possibly spotlight precisely how missteps can lead to disastrous consequences for developing embryos.

John F. Rawls, Ph.D.John F. Rawls, Ph.D., received a doctorate in developmental biology from Washington University in 2001.  He remained there for his postdoctoral studies until 2006, then accepted a position as an assistant professor of cell and molecular physiology at the University of North Carolina, Chapel Hill.  Dr. Rawls will explore how bacteria that inhabit the gut can promote health.  In recent years, researchers have come to recognize the importance of normal intestinal flora, particularly in regard to regulating metabolism and providing immunity.  However, little is known about how these bugs influence these key processes in their hosts.  As a postdoctoral fellow, Dr. Rawls developed and cultivated a special, germ-free strain of zebrafish lacking its usual intestinal flora.  The gut of this germ-free zebrafish can be populated with whatever microbe the researcher would like to study.  Coupling this novel experimental animal with state-of-the-art molecular and genetic techniques, Dr. Rawls plans to identify bacterial genes that regulate nutrient metabolism and innate immunity in the zebrafish.  In preliminary studies, he determined that zebrafish populated with bacteria that lack functional flagella (the tails they use to swim) have impaired immunity, which suggests that flagellar proteins—or bacterial locomotion—somehow promote a normal immune response.  Expanding on these studies, Dr. Rawls intends to survey some 4,600 different bacterial genes, searching for those that play a role in metabolism or immunity.  His findings could expand our understanding of host-microbe relationships, which could lead to novel therapies for restoring and maintaining human health.

Seth M. Rubin, Ph.D.Seth M. Rubin, Ph.D., received a doctorate in chemistry from the University of California, Berkeley in 2003.  He performed postdoctoral research at the Memorial Sloan-Kettering Cancer Center until 2006, then joined the faculty at the University of California, Santa Cruz as an assistant professor of chemistry and biochemistry.  Dr. Rubin will study how a protein found in rare childhood eye tumors influences cell division and the development of cancer.  This so-called retinoblastoma protein (Rb) serves in normal cells as a molecular “brake” that controls whether a cell will multiply.  When that brake is defective, cells proliferate without restraint to form tumors.   Rb holds proliferation in check by holding hostage a regulatory protein called E2F, preventing it from switching on the genes necessary for cell division.  Under normal circumstances, Rb activity is controlled by a chemical alteration called phosphorylation.  When a cell is ready to divide, Rb becomes phosphorylated, and in this form, it cannot interact with E2F.  So E2F can turn on the cell-division program, and when that is complete, phosphorylation disappears and Rb once again grabs hold of E2F.  As a postdoctoral fellow, Dr. Rubin began to dissect how phosphorylation disrupts the association between Rb and E2F.  Now, combining a diverse array of biophysical, biochemical, structural and cell biological techniques, Dr. Rubin will try to detail exactly how the addition—and removal—of this chemical alteration influences the interaction of Rb and E2F, and determine how these processes are regulated within the cell.  This work could lead to new approaches to understanding how cells regulate their proliferation and inhibit the formation of tumors.

Holger Sondermann, Ph.D.Holger Sondermann, Ph.D., received a doctorate in biochemistry from the Max-Planck Institute of Biochemistry in Germany in 2001.  He did a brief postdoctoral fellowship at the Rockefeller University before continuing his training at the University of California, Berkeley from 2001 to 2005.  He then accepted a position as an assistant professor in molecular medicine at Cornell University.  Dr. Sondermann will investigate how harmful bacteria are able to form biofilms—microbial blankets that shelter their residents from attack by antibiotics.  Such hard-to-treat biofilms underlie the chronic lung infections that plague people with cystic fibrosis and can coat the surfaces of artificial joints and other implants, necessitating their replacement.  Although several genes needed for biofilm formation have been identified, little is known about the molecular signals that bacteria use to invite their neighboring microbes to join together in a complex, stable multicellular community.  One key player appears to be a small molecule called cyclic di-GMP that regulates cell adhesion and movement in bacteria.  Using state-of-the-art structural, biochemical and molecular biological techniques, Dr. Sondermann will explore how cyclic di-GMP—along with the enzymes that produce and destroy it—allow the infectious bacterium Pseudomonas aeruginosa to produce a biofilm.  His work could lead to the development of novel antibiotics for eradicating difficult-to-treat infections.

Michael A. Sutton, Ph.D.Michael A. Sutton, Ph.D., received a doctorate in neuroscience from Yale University in 2002.  He was a postdoctoral fellow at the California Institute of Technology from 2002 to 2006, after which he accepted a position as an assistant professor of neuroscience at the University of Michigan.  Dr. Sutton will investigate the molecular changes that drive the progression of epileptic disorders.  Epilepsy stems from the abnormal activation of small sets of neurons in the brain; these localized disturbances then spread throughout the brain, precipitating seizures.  While a postdoctoral fellow, Dr. Sutton observed that inhibiting the low-level, background communication that occurs between neurons can destabilize them and cause them to become overly excitable—a hallmark of epilepsy.  It also causes them to produce an unusual type of receptor protein: one that responds to the same excitation-producing brain chemical as normal receptors, but that also permits calcium to enter the cell.  This calcium boost can excite the neuron further still; overstimulation that could foster seizure-like activity or cause nerve damage or death.  Using powerful molecular techniques he developed for tracking the presence of these odd receptors in neurons in brain slices and in culture, Dr. Sutton will explore whether their appearance and persistence represent an early event along the road to epilepsy—and whether blocking the activity of these receptors can ameliorate the severity of seizure-related neuronal activity.  His work could lead to a deeper understanding of the causes of and treatments for epilepsy.

Benjamin R. tenOever, Ph.D.Benjamin R. tenOever, Ph.D., received a doctorate in virology from McGill University in 2004.  He engaged in postdoctoral research at Harvard University from 2004 to 2007, then joined the staff at the Mount Sinai School of Medicine as an assistant professor of microbiology.  Dr. tenOever wants to better understand the host-pathogen interactions that occur when the influenza virus is introduced into an animal.  Host cells first respond to viral entry by producing a molecule called type I interferon (IFN-I).  This powerful signaling molecule then unleashes a barrage of additional molecules that render neighboring cells more resistant to infection.  Those second-line molecules include antiviral proteins as well as a unique set of microRNAs (miRNAs), one of which Dr. tenOever has found to have direct antiviral activity of its own.  Upon encountering a virus, cells that are thus primed for battle—already producing antiviral proteins and miRNAs—will secrete yet additional signaling molecules that summon more immune cells to help fight the intruder.  These backup troops then secrete signals of their own, often producing a so-called “cytokine storm”—a flurry of communications that can overwhelm the system and sometimes kill the host.  Using an array of advanced molecular and cell biological techniques, Dr. tenOever hopes to define the role that miRNAs play in the war against influenza infection.  He also will explore how cells respond when confronted with sometimes conflicting signals generated during the “cytokine storm”.  That decision may rest, in part, on the activity of another protein that Dr. tenOever has found is key to cellular defense.  Taken together, Dr. tenOever’s work could provide significant new information about how viruses and host cells interact, which in turn could lead to the development of novel antiviral therapeutics.

Leor S. Weinberger, Ph.D.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.

Julia Zeitlinger, Ph.D.Julia Zeitlinger, Ph.D., received a doctorate in biochemistry from the European Molecular Biology Laboratory in Germany in 2000.  She engaged in postdoctoral studies at the Whitehead Institute for Biomedical Research from 2000 to 2007, then joined the staff of the Stowers Institute for Medical Research in Kansas City as an assistant investigator.  Dr. Zeitlinger will examine how regulatory proteins promote cellular memory—the means by which cells maintain their identity.  When a liver cell divides, it produces another liver cell—not a muscle cell or any other kind of cell.  To do that, the cell must manufacture the proteins made by a liver cell, and avoid making proteins related to other cells.  But the cells that give rise to a specialized cell like a liver cell, called progenitor cells, must be more flexible.  Unlike specific cells, they remain uncommitted as to type until they receive a signal to switch on the appropriate genes for making one type of cell and permanently shut down the inappropriate ones.  Previously, Dr. Zeitlinger discovered that the flexibility of progenitor cells is maintained by a pair of proteins: polycomb, which represses gene activity, and Pol II, which activates genes.  In fruit fly embryos, regulatory genes that will be switched on later in development—for example, the genes that instruct a muscle cell to become a muscle cell—are decorated with both of these proteins.  However, the Pol II associated with these genes is “stalled”, meaning not that it has shut down, but that it sits on the DNA, like a car at a red light, waiting for a signal to turn the gene on.  Using state-of-the-art techniques in genetics and molecular biology, Dr. Zeitlinger hopes to learn when and where Pol II stalls during embryonic development, and examine whether polycomb proteins might be involved.  Her work could lead to a deeper understanding of how cells set their genetic programs during development, and how errors in the programs can contribute to human diseases such as certain types of leukemias.

Hui Zong, Ph.D.Hui Zong, Ph.D., received a doctorate in biochemistry and cell biology from Indiana University School of Medicine in 2001.  He performed postdoctoral studies at Stanford University, and in 2006 was appointed an assistant professor of biology at the University of Oregon.  Dr. Zong will explore what occurs in the very earliest stages of tumor formation.  Many cancers are initiated by the inactivation of tumor-suppressor genes that encode proteins that normally keep cell growth and division in check.  Without these molecular brakes, cells begin to divide without restraint, accumulating additional cancer-promoting mutations and ultimately forming tumors.  But the earliest events in this molecular cascade—including the initial loss of tumor suppressor activity—are nearly impossible to study, because by the time a tumor can be detected, many additional molecular derangements have occurred.  During his postdoctoral fellowship, Dr. Zong developed and tested a cutting-edge technique that sporadically shuts down tumor suppressor genes in the cells of live mice and labels the resulting mutant cells with a fluorescent marker protein that allows them to be detected within hours of their formation.  Using this system, Dr. Zong will examine what role the tumor-suppressor p53 plays in the initiation of brain tumors.  Specifically, he wants to learn whether cells lacking p53 proliferate more rapidly in certain brain regions; if they fare better when they are closer to nourishing blood vessels; and whether they coerce neighboring cells into providing a more tumor-friendly environment.  His findings could lead to new strategies for the early detection and treatment of tumors, perhaps even before they become malignant.

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