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Heads of Laboratories

Head shot of Charles Rice
Charles M. Rice, Ph.D.
Maurice R. and Corinne P. Greenberg Professor in Virology
Laboratory of Virology and Infectious Disease
Charles.Rice@rockefeller.edu

Millions of people are infected with hepatitis C virus or hepatitis B virus, which cause liver cancer and liver failure. In addition, significant morbidity and mortality are caused by other RNA viruses such as dengue and chikungunya virus. Dr. Rice’s lab works to understand virus replication and innate immune responses that limit infection. His group is also developing new in vitro culture and animal models to facilitate this work.

Hepatitis C virus (HCV) infects the liver and is a major cause of cirrhosis and liver failure. Conventional virus culture methods are unsuccessful for HCV, and researching it has required creative new approaches. Dr. Rice is among those who pioneered such techniques, and his group continues to unravel how HCV infects liver cells, replicates, assembles, and causes disease. Ongoing studies in his lab include how the virus exploits hepatocyte lipid processing and protein secretory pathways to promote its own growth. These and other findings are being applied to develop new technologies, such as 3D culture and induced pluripotent stem cell culture, which will be used to efficiently grow HCV and other viruses.

The Rice lab also studies the host side of the virus-cell interface, and has identified and characterized host proteins that make cells permissive for infection by HCV. In addition, cellular micro RNAs, which are important in translational control, also regulate HCV RNA in liver cells. With innovative bioinformatic methods that map these interactions with unprecedented precision, the Rice lab has discovered further complexities in the relationship between host and pathogen.

Dr. Rice’s work on HCV can be applied to other liver viruses, such as hepatitis B virus (HBV), which is often refractory to antiviral treatment due to the persistence of the viral genome as covalently closed circular DNA (cccDNA). The Rice lab’s development of a mouse model with a human liver and immune system, as well as new in vitro culture methods, are revealing new strategies to potentially target cccDNA. For both HBV and HCV, drug resistance often occurs following antiviral therapy, and is a subject of study by the Rice group and collaborators.

It has long been recognized that the immune response to pathogens includes an innate component rapidly activated upon infection. Dr. Rice’s group studies how virus infection impacts pathways induced by interferon, which triggers innate immune responses. For this work, Dr. Rice has developed high throughput screening assays to identify interferon-stimulated genes (ISGs) that limit, or in some cases, enhance virus infection. The timing and function of ISGs are important determinants of the infection outcome, and understanding how they work may lead to improvements in prevention and treatment of infection. Although induction of ISG pathways may occur after infection by multiple types of viruses, the Rice lab has focused on those that are global health concerns, such as HCV, HBV, influenza A, dengue, yellow fever, and chikungunya. Collectively, these pathogens are responsible for hundreds of millions of infections, and enormous human suffering every year.

In studies led by research associate professor Margaret R. MacDonald, the mechanistic details of an ISG known as zinc-finger antiviral protein (ZAP) are under investigation. ZAP potently inhibits alphavirus and filovirus replication, and how it functions with other ISGs will reveal another aspect of virus-cell engagement. Dr. MacDonald is also investigating the role of cellular chaperone proteins in flavivirus RNA replication.


EDUCATION

B.S. in zoology, 1974
University of California, Davis

Ph.D. in biochemistry, 1981
California Institute of Technology

POSTDOC

California Institute of Technology, 1981–1985

POSITIONS

Assistant Professor, 1986–1990
Associate Professor, 1991–1995
Professor, 1995–2000
Washington University School of Medicine

Professor, 2000–
Scientific and Executive Director, Center for the Study of
Hepatitis C, 2000–
The Rockefeller University

AWARDS

Lasker-DeBakey Clinical Medical Research Award, 2016

Robert Koch Award, 2015

Pew Biomedical Scholar, 1986

M.W. Beijerinck Virology Prize, 2007

MEMBERSHIPS

National Academy of Sciences
American Academy of Arts and Sciences
Fellow, American Association for the Advancement of Science

SELECTED PUBLICATIONS

Luna, J.M. et al. Hepatitis C virus RNA functionally sequesters miR-122. Cell 160, 1099–1110 (2015).

Dittmann, M. et al. A serpin shapes the extracellular environment to prevent influenza A virus maturation. Cell 160, 631–643 (2015).

Shlomai, A. et al. Modeling host interactions with hepatitis B virus using primary and induced pluripotent stem cell-derived hepatocellular systems. Proc. Natl. Acad. Sci. U.S.A. 111, 12193–12198 (2014).

Sheahan, T. et al. Interferon lambda alleles predict innate antiviral immune responses and hepatitis C virus permissiveness. Cell Host Microbe 15, 190–202 (2014).

Schoggins, J.W. et al. Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity. Nature 505, 691–695 (2014).


Dr. Rice is a faculty member in the David Rockefeller Graduate Program and the Tri-Institutional M.D.-Ph.D. Program.