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The 2009 Early Career Physician Scientists

Summary

Brief bios of the 2009 Early Career Physician Scientists.

Edward Behrens, M.D.
Children's Hospital of Philadelphia
Philadelphia, PA
HHMI Medical Fellows Program

Edward Behrens, a pediatric rheumatologist, is trying to understand what guides the immune system’s "decision" to attack its own tissues. His research has already led to important discoveries about how the immune system goes haywire in children who have juvenile arthritis and other autoimmune diseases. Behrens focuses on dendritic cells, which initiate the immune system’s response to foreign invaders, but they can also trigger autoimmune or autoinflammatory disorders if they are improperly activated. His recent research has focused on proteins called toll-like receptors inside dendritic cells, which he thinks help spark macrophage activation syndrome, a deadly complication of juvenile arthritis. Behrens is also developing computational tools to improve the collection and tracking of healthcare information about patients with autoimmune diseases. He recently assembled a large database of information about juvenile arthritis patients, which he and his colleagues have used to discover new genetic variations linked to the disease.


Sunjay Kaushal, M.D., Ph.D.
Northwestern University
Chicago, IL
HHMI Medical Fellows Program

Cardiovascular disease is the leading cause of death in the United States, with an estimated cost of $300 billion per year. One attractive alternative to current therapies, such as heart valve replacement, is to engineer new tissues to replace parts of a damaged heart. Sunjay Kaushal is on the frontlines of this nascent field, and he's using tissue engineering to build new hearts and valves in the laboratory. He is also a pediatric cardiac surgeon who operates on patients with a wide variety of congenital heart defects. His experience as a heart surgeon has given him a unique perspective on why valves fail and what can be done to improve them. Kaushal's interest in tissue engineering blossomed when he was a postdoctoral fellow at Harvard University and devised a new method for building engineered blood vessels using endothelial progenitor cells, a type of bone marrow cell. Kaushal is now planning to engineer a heart valve, starting with the cellular scaffolding from a pig heart. He will build the valve, testing different types of cells to finds those that are strong enough to replicate the strength of human heart muscle. His long-term goal is to use tissue engineering to build an entire heart.


Erin Kershaw, M.D.
University of Pittsburgh
Pittsburgh, PA
HHMI Medical Fellows Program

As a child, Erin Kershaw was surprised by the way society treated obese people. It wasn't until college—when she began to learn more about obesity in a course on body weight—that she began to appreciate it as a complex “medical disease.” She decided to become a doctor specializing in obesity issues, but soon realized that there were few effective clinical treatments for obesity. Since then, Kershaw has focused her career on research into obesity and metabolic syndrome, a cluster of conditions that includes the most dangerous heart attack risk factors: pre-diabetes, diabetes, high blood pressure, and changes in fats in the blood, like cholesterol. Her long-term goal is to develop new therapies for preventing and treating these diseases. She plans to build on work that she had begun as a postdoctoral fellow, where she identified two genes that regulate how fats are broken down. The genes may play a role in metabolic syndrome, and Kershaw plans to use both mouse and cellular studies to investigate how lipid toxicity may contribute to obesity and metabolic diseases.


Tamara Lotan, M.D.
Johns Hopkins University
Baltimore, MD
HHMI-NIH Research Scholars Program

On many levels, prostate cancer cells re-enact the events of early prostate development as they invade and migrate through normal tissues. By understanding the signals that help normal prostate cells to move into the right place at the right time in the embryo, pathologist Tamara Lotan hopes to learn how these same signals may enable prostate cancer cells to migrate and invade healthy tissue. Her work focuses on the role of tumor suppressor gene PTEN in guiding cell migration during early development of the prostate gland. While PTEN is known to be a potent tumor suppressor, the protein’s function in normal and cancerous cell migration is still unclear. Lotan is using state-of-the-art microscopes to make time-lapse movies of prostate cells as they move into position, as well as examining mouse and Petri dish models to find out what happens when PTEN is missing. The studies may help clarify why PTEN is important for normal prostate development and may possibly explain why loss of PTEN is common in prostate cancer.


Anne Manicone, M.D.
University of Washington
Seattle, WA
HHMI-NIH Research Scholars Program

Anne Manicone, a pulmonary and critical care physician, is studying lung inflammation, the lung's natural response to injury or infection. Although a necessary part of fighting infection, lung inflammation can become a life-threatening complication. It is a contributor to a number of pulmonary diseases, including cystic fibrosis, acute respiratory distress syndrome, emphysema, and pulmonary fibrosis, so it is critical that researchers develop a better understanding of its progression. Manicone is interested in a class of proteins called MMPs (matrix metalloproteinases), which are vital to the immune system. Epilysin, a recently discovered MMP, is found in macrophages, white blood cells that serve several critical roles in the immune system, including engulfing and killing bacteria. She has found that macrophages that lack epilysin migrate to injured or infected lung tissue faster than normal macrophages, and therefore create an inflammatory response more rapidly. Manicone thinks epilysin may hold a key to understanding how to restrain lung inflammation. She is now poised to use gene expression and proteomic tools to learn how epilysin controls macrophage migration and influences immune responses.


Miguel Rivera, M.D.
Massachusetts General Hospital
Boston, MA
HHMI Medical Fellows Program

Researchers are just beginning to understand how and why certain critical genes involved in embryonic development might also set the stage for pediatric cancer. But pathologist Miguel Rivera has already uncovered several important leads. He identified WTX, a tumor suppressor gene that is deleted or mutated in about a third of cases of Wilms tumor, the most common kidney cancer in children. WTX is expressed in kidney stem cells, and Rivera suspects the protein is important for proper kidney development. He also has a hunch that further study of WTX and related pathways could lead to new insights about the link between cancer and normal development. Using mouse and cell culture models, Rivera is now investigating the function of WTX and hopes to determine whether WTX and certain closely related genes are involved in other childhood cancers. WTX is the first tumor suppressor gene found on the X chromosome, and Rivera wants to find out if that chromosome harbors other tumor suppressor genes and to identify new genes that might be involved in pediatric cancer.


Adam Rosendorff, M.D.
University of Pittsburgh
Pittsburgh, PA
HHMI Medical Fellows Program

As an undergraduate at the University of the Witwatersrand in South Africa, Adam Rosendorff’s interests ranged from comparative literature to philosophy to economics. Rosendorff, who is now a clinical pathologist, is bringing his wide-ranging curiosity to learning how the Epstein-Barr virus can spawn leukemia and lymphoma. Epstein-Barr is a common virus that infects most people at some point in their lives. Some of those infected with the virus develop infectious mononucleosis, but many people do not show any symptoms at all. However, people with suppressed immune systems—such as transplant recipients or AIDS patients—who are infected with Epstein-Barr virus have a much greater risk of developing cancer later. In some cases, white blood cells infected with Epstein-Barr can survive infection and continue to divide, which leads to the development of leukemia or lymphoma. Rosendorff wants to understand how viral infection keeps the protein-making machinery running in infected cells, preventing cell death and allowing cells to multiply. He hopes this will lead to new drugs to treat Epstein-Barr-associated cancers.


Edward Schaeffer, M.D., Ph.D.
Johns Hopkins University School of Medicine
Baltimore, MD
HHMI-NIH Research Scholars Program

After his grandfather died of prostate cancer, Edward Schaeffer decided to pursue a career in research to help discover new cancer treatments for the many men, like his grandfather, who couldn’t be cured by existing surgical and pharmaceutical therapies. As co-director of the Prostate Cancer Multi-Disciplinary Clinic at Johns Hopkins, Schaeffer is part of a team of urologists, medical and radiation oncologists, and pathologists that works together to best tailor treatments for individual patients. In the lab, Schaeffer is examining whether the same pathways that drive embryonic prostate development are also be involved in prostate cancer. He was drawn to this area of study because both cancer and development require male sex hormones call androgens. Schaeffer and his team have identified several new growth pathways that connect the two, and suggested that a molecule called PLA2 might link androgen-driven prostate cancer growth and prostate inflammation. Schaeffer hopes that further research on inflammation, androgens, and developmental pathways may lead to new targeted therapies for prostate cancer.


Nima Sharifi, M.D.
University of Texas Southwestern Medical Center
Dallas, TX
HHMI Medical Fellows Program

Prostate cancer is the leading cause of cancer and the second leading cause of cancer mortality in men in the United States. These dismal statistics motivate Nima Sharifi's search for new treatments for prostate cancer. Sharifi, an oncologist, is studying how androgen receptors fuel the growth of prostate tumors. Advanced prostate cancer is often treated with androgen deprivation therapy (ADT), which shuts off the tumor's access to androgen, a male hormone. But over time the cancer becomes resistant to this treatment. Previous research suggested that androgen receptors are reactivated by "gain-of-function" changes, which allow the tumors to become resistant to ADT. After tumors cease responding to ADT, they gradually turn into a lethal form of prostate cancer. Sharifi is studying how other proteins collaborate with androgen receptors to become reactivated after treatment with ADT. He hopes to develop a second-line drug therapy that targets the androgen pathway and shuts down growth of ADT-resistant prostate cancer.


C. Shad Thaxton, M.D., Ph.D.
Northwestern University
Chicago, IL
HHMI Medical Fellows Program

During his third year of medical school, Shad Thaxton read a Scientific American article about nanotechnology that changed his life. The ideas presented in the article inspired him to seek out Northwestern University’s Chad Mirkin, a leader in the field of nanotechnology. As an HHMI medical student fellow in Mirkin's lab, Thaxton developed the “bio-barcode assay,” an ultra-sensitive protein detector using gold nanoparticles as probes. He used the technology to detect prostate specific antigen (PSA), a biomarker associated with prostate cancer. The bio-barcode detects prostate cancer recurrence more quickly than conventional PSA tests. With Mirkin's encouragement, Thaxton decided to complete his Ph.D. while simultaneously pursuing his surgical residency in urology—an unusual and difficult path. Now he is using nanotechnology to evaluate the bio-barcode effectiveness finding recurrent prostate cancer in clinical trials. Thaxton has also set his sights on using nanotechnology in cardiovascular disease research. He's already created a nanoparticle that mimics high-density lipoprotein (HDL, the “good cholesterol”), an achievement that received international media attention. He hopes to develop new nano-sized drugs for preventing and treating damage to arteries caused by cholesterol buildup.


Brian Wolpin, M.D., M.P.H.
Dana-Farber Cancer Institute
Boston, MA
HHMI Medical Fellows Program

Pancreatic cancer kills about 95 percent of those diagnosed with the disease. Smoking is a known risk factor, but diabetes, obesity, and family history also increase a person's chance of developing this deadly cancer. Given this poor prognosis, physician and epidemiologist Brian Wolpin is working to identify genetic and lifestyle factors that predispose people for pancreatic cancer. He is analyzing large amounts of data from epidemiologic studies, comparing information about diet, physical activity, blood biomarkers, and inherited genetic information from people with pancreatic cancer to similar data from healthy individuals. Wolpin has already used this strategy to discover that the gene responsible for determining blood type is also involved in nearly 20 percent of pancreatic cancers. He hopes to reveal additional risk factors for pancreatic cancer that could help in identifying high-risk individuals before they develop the disease.

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