Lopa Mishra: Improving Transplant Outcomes through Clinical and Translational Research

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Physicians on Georgetown University Hospital’s transplant team are actively involved in basic and clinical research studies that may lead to improved patient care in the future. Among current investigations are several protocols related to hepatobiliary disease, liver cancer, immunology and ethnic differences in transplant success.

Lynt Johnson, MD, chief, Division of Transplant Surgery at Georgetown, and Kirti Shetty, MD, medical director of Liver Transplantation, are working with GUMC’s Lopa Mishra, MD, PhD, to define the molecular mechanisms that cause liver cancer, with particular emphasis on the role of cancer stem cells. The incidence of liver cancer in the United States has grown rapidly over the past few decades, generating an urgent need for better understanding and more definitive therapies for this dreaded complication of cirrhosis.

Dr. Mishra recently received a five-year, $7.5 million grant from the National Cancer Institute to further study this and other cancers of the “foregut”—pancreatic, gastric (stomach), and hepatocellular (liver). In many parts of the world, stomach and liver cancers are among the most common tumors diagnosed, and in the United States, pancreatic cancer is considered amongst the most deadly. All are difficult to treat because surgery is considered the most effective option but too often, these types of tumors are discovered after they are too advanced for a surgical cure.

“This is uniquely exciting research because it represents a wonderful collaboration of clinicians and basic scientists across disciplines who are dedicated to improving the outcome of patients with these cancers,” says Stephen R.T. Evans, MD, chairman and professor in the Department of Surgery.

Since liver transplantation is curative in the early stages of liver cancer, researchers at the Georgetown Transplant Institute are focusing now on strategies for early identification of at-risk patients. In the future, they also hope to develop agents that interfere with the genetic pathways of carcinogenesis.

Joseph Keith Melancon, MD, Georgetown’s new director of the Kidney and Pancreas Transplantation Program, is conducting epidemiologic studies into the disparities in transplant outcome and immune response across racial, gender and socio-economic lines.

“Following a transplant, we know that African Americans do not fare as well as other groups, women do not fare as well as men and Asians do better than anyone across the board,” he says. “But we don’t really know why. If we can understand what causes these outcome disparities, we can improve patient care.”

Work conducted in the immune lab of Thomas Fishbein, MD, director of Georgetown’s Intestinal Transplant and Pediatric Liver Transplant Program, is already leading the way to improved care and outcomes for intestinal transplant patients. His innovative research is changing the way transplant surgeons prepare donor intestines, and was the subject of a feature article by the scientific journal Nature in 2008.

By Leslie Whitlinger, excerpted from the Fall 2008 issue of Georgetown Physician Update

Photography done by Herman Farrer