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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 or hepatitis B viruses, which cause liver cancer and liver failure. Meanwhile, other RNA viruses such as Zika, yellow fever, dengue, and chikungunya cause significant morbidity and mortality. 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 creative new approaches have been required to study it. 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 are revealing how the virus exploits hepatocyte lipid 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 cells. With innovative bioinformatic methods that map these interactions with unprecedented precision, the lab has discovered further complexities in the host-pathogen relationship.

Rice’s work on HCV can be applied to other liver viruses, such as the hepatitis B virus (HBV), which is often refractory to treatment due to viral genome persistence as a covalently closed circular DNA (cccDNA). His team’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.

It has long been recognized that the immune response to pathogens includes an innate, rapidly activated component. Rice’s group studies how infection impacts pathways induced by interferon, triggering innate immune responses. To conduct these investigations, Rice has developed high-throughput screening assays to identify interferon-stimulated genes (ISGs) that limit—or, in some cases, enhance—virus infection. Understanding how ISGs work may lead to improvements in prevention and treatment of infectious diseases. In that context, the Rice lab has focused on viruses of global health concern, such as HCV, HBV, influenza A, dengue, yellow fever, Zika, and chikungunya. Collectively, these pathogens are responsible for hundreds of millions of infections, and enormous human suffering every year. Another area currently under investigation is the mechanisms of attenuation of the yellow fever vaccine, and the possible human genetic causes of a rare yellow fever-like illness that can occur after vaccination.

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. MacDonald, in collaboration with others, is also investigating the human antibody response to the Zika virus with the goals of developing an antibody reagent for therapeutic use, while gaining insight into successful immune responses that will guide vaccine development.



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

Pew Biomedical Scholar, 1986

M.W. Beijerinck Virology Prize, 2007

Robert Koch Award, 2015

InBev Baillet Latour Health Prize, 2016

Lasker-DeBakey Clinical Medical Research Award, 2016

MEMBERSHIPS

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

SELECTED PUBLICATIONS

Billerback, E. et al. Mouse models of acute and chronic hepacivirus infection. Science 357, 204–208 (2017).

Robbiani, D.F. et al. Recurrent potent human neutralizing antibodies to Zika virus in Brazil and Mexico. Cell 169, 597–609 (2017).

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).

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.