Rockefeller virologists and MIT tissue engineers receive $5.8 million NIH grant to study hepatitis

Scientists studying hepatitis at Rockefeller University and the Massachusetts Institute of Technology will receive a $5.8 million grant to study hepatitis infection under the National Institutes of Health’s inaugural Transformative R01 grant program, a groundbreaking initiative designed to encourage high-risk research. The grant, which will run for five years beginning in 2009, will fund efforts to elucidate the notoriously complex mechanisms underlying disease progression in hepatitis B and C virus infection.

Chronic infections with hepatitis B and C viruses, which take root in the liver, affect an estimated 500 million people worldwide, leading to diseases including hepatitis, cirrhosis, liver failure and cancer, and causing more than 1.5 million deaths each year. Though a vaccine and several drugs that target the hepatitis B virus exist, there are no vaccines for hepatitis C, and numerous obstacles stand in the way of developing treatments. Both viruses, for example, employ robust replication systems that are difficult to permanently disrupt. The hepatitis C virus, furthermore, has already exhibited resistance to antiviral drugs currently available to help fight it. Coinfection with both viral strains is relatively common, compounding their individual impacts. And scientists do not currently have in vitro or in vivo models that accurately imitate human liver biology and pathogenesis, which would help facilitate research.

In collaboration with Sangeeta N. Bhatia, professor in the Harvard-MIT Division of Health Sciences and Technology, researchers in Rockefeller’s Laboratory of Virology and Infectious Disease, headed by Charles M. Rice, Maurice R. and Corinne P. Greenberg Professor, first aim to address this last issue by refining cell culture techniques recently developed by Bhatia and Salman Khetani, a former postdoctoral associate in Bhatia’s laboratory who is now director of research at Hepregen. Recent investigations with such cultures by Alexander Ploss, a research associate in the Rice lab, have already revealed important insights about the disease progression of the two viruses. The team is also developing three-dimensional human liver organoids for use in mice reconstituted with a human immune system. With these tools, Rice, Bhatia, Ploss and their colleagues propose to characterize hepatitis B and C infections, to clarify how they influence each other on both the cellular and systemic levels and, ultimately, to inform the development of novel preventive and therapeutic remedies.

The Transformative R01 (TR01) program was launched this year under the NIH Roadmap for Medical Research, an umbrella program established in 2004 to identify and address traditional roadblocks to innovative research. TR01 grants support exceptionally innovative, high-risk, original and/or unconventional research projects that have the potential to create or overturn fundamental paradigms. These projects tend to be inherently risky, but if successful can profoundly impact a broad area of biomedical research.

Before joining Rockefeller University in 2000, Rice completed his Ph.D. in biochemistry and postdoctoral studies at the California Institute of Technology and served on the faculty of the Washington University School of Medicine for 14 years. Rice is the executive and scientific director of the Center for the Study of Hepatitis C, an interdisciplinary center established jointly by Rockefeller, NewYork-Presbyterian Hospital and Weill Cornell Medical College. Rice is a member of the National Academy of Sciences.

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