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Research Profile: Mark Feitelson
Professor, Department of Mathematics; Co-Director, Biotechnology Center
Mark Feitelson, Professor in the Department of Biology and Co-Director of the Temple University Biotechnology Center at Temple since 2007, focuses his research on the hepatitis B and C viruses and their role in engendering liver cancer.
The hepatitis B virus (HBV) is among the most common infections in the world. Transmitted through bodily fluids, it has infected approximately 2 billion people — roughly one third of the earth's population — mostly in developing countries in Asia and Africa. More than 350 million people are chronically infected, including about 110 million Chinese people, or 10% of the nation's population. Hepatitis B doesn't appear on any list of the world’s deadliest diseases because the infection itself is rarely fatal. But long-term HBV and hepatitis C virus infections result in chronic liver disease (hepatitis), cirrhosis (end-stage liver disease) and liver cancer, the third most common cause of death from cancer worldwide.
One product of the virus, known as the hepatitis B X antigen (HBxAg), plays a major role in the life cycle of HBV and is an important contributor to the development of liver cancer. HBxAg has been the focus of Feitelson's research since 1983. HBxAg stimulates the production of virus proteins that are involved in enlisting the cell to create more viruses. During chronic HBV infection, it also protects infected liver cells from destruction by the immune system. The immune system's response to the virus, stymied by the actions of HBxAg, results in the development of inflammatory liver disease (chronic hepatitis) without eliminating the virus-infected cells.
Sustained virus replication and progressive chronic liver disease are major risk factors for the appearance of liver cancer. Over the years, the focus of Feitelson's research has been how HBxAg promotes the survival of virus-infected cells which, like cancer cells, often survive despite the persistence of immune responses that would otherwise eliminate such cells. His lab has also identified events triggered by HBxAg that are important contributors to cancer development.
In effect, the hepatitis B and C viruses cause their host cells to acquire the quick growth and resistance to immune elimination characteristics of cancer cells in the course of promoting their own survival. Liver cancer itself often follows.
The current model for managing aggressively mutating viral infections is combination therapies, or "drug cocktails." Highly successful in treatment of the human immunodeficiency virus (HIV), this approach uses drugs aimed at multiple chemical targets on the virus to suppress replication to such low levels for such a long time that the virus cannot reach the critical mass of mutated forms required to repopulate around the drugs. Feitelson thinks HBxAg might be a good additional target for HBV drugs.
Continuously funded by the National Institutes of Health (NIH) since 1988, Feitelson recently received a grant to develop combination therapies for HBV. He is currently working on a total of three NIH-funded projects and has received funding from industry and foundations over the years for multiple translational and applied research projects.
One such industrial contract is from the Chinese company HEC, which has enlisted Feitelson to test a promising new HBV drug with a new target in his lab. HBV receives relatively little attention in the West due to the low infection rates in Europe and the Americas and the delayed impact of the virus on the health of infected people. But HBV-associated diseases are a national priority in China, and Feitelson has formed strong ties with the HBV research community there as he helps to fight these diseases. Many of his graduate students are from China and he often travels there for conferences and consultations. He has been a visiting professor at five different Chinese Universities, including the elite Fudan University in Shanghai.
Feitelson has even formed a small company in China called Usino to aid in accomplishing one of his goals; helping China to develop their own drugs for HBV, which could then be made available at affordable prices. Usino is presently helping to standardize clinical testing throughout China, laying the groundwork for advanced drug development, but the company also facilitated the HEC contract.
Feitelson earned a BS in biology from the University of California, Irvine in 1974 and a PhD in Microbiology and Immunology from the UCLA School of Medicine in 1979 before becoming an American Cancer Society postdoctoral fellow in the Department of Medicine at Stanford University from 1980-1982. He was then recruited to Fox Chase Cancer Center by Nobel Laureate Baruch Blumberg, who discovered HBV and developed the test and vaccine used around the world. He moved to the faculty at Thomas Jefferson University from 1991 to 2007.
(posted July 2009)
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