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Millions of people are infected with hepatitis C and B viruses (HCV, HBV), which cause liver cancer and liver failure. RNA viruses like Zika, yellow fever, dengue, chikungunya, and SARS-CoV-2 also cause significant morbidity and mortality. Rice’s lab works to understand virus replication mechanisms and innate immune responses that limit infection. His group is also developing new in vitro culture systems and animal models to facilitate this work.

Many viruses, including the hepacivirus HCV, are challenging to culture and new approaches are required to study them. Rice’s group identified critical sequences in the HCV genome required for infectivity, demonstrated it was a causative agent of hepatitis, and pioneered novel cell culture methods for growing and studying it. This and other work was seminal in developing the antiviral drugs now used to cure HCV. Despite this success, a vaccine is still sorely needed. To this end, Rice’s group has established the first immunocompetent mouse model for hepacivirus infection using the Norway rat hepacivirus, which replicates key aspects of liver disease observed in HCV-infected humans, including cancer. The lab also uses human liver chimeric mice to study the roles of diet and human genetics in fatty liver disease, yellow fever vaccine attenuation mechanisms, and the human genetic causes of rare but serious post-vaccine disease. Trained immunity, or how exposure to one pathogen can result in resistance to an unrelated pathogen, is another area of active interest.

The Rice lab also studies virus-host interactions to learn how factors limit or facilitate virus replication. Responses to viral pathogens include an innate, rapidly activated expression of proteins called interferons. Rice’s group has developed high-throughput screens to identify interferon-stimulated genes (ISGs) that limit or, in some cases, enhance virus infection, focusing on viruses of global health concern such as HCV, HBV, influenza A, dengue, yellow fever, Zika, chikungunya, and coronaviruses. The group has also used CRISPR technology to systematically knock out human genes to identify those whose loss affects viral infection. Ultimately, a better understanding of virus-host biology may reveal novel therapeutic targets and improve disease prevention and treatment.

Research Associate Professor Margaret R. MacDonald leads studies using cellular and animal models to investigate Powassan virus (POWV), a tick-borne flavivirus causing severe encephalitis in the United States. In collaborative efforts, she explores human antibody responses to flaviviruses to develop therapeutic antibody reagents and gain insights for vaccine development. She also collaborates to develop nanobodies against POWV and the Lyme disease spirochete for potential diagnostics or therapeutics.

Research Assistant Professor Hans-Heinrich Hoffmann leads investigations on how mosquito-borne and tick-borne viruses navigate infection in both vertebrate and invertebrate cells. His work includes conducting genome-wide CRISPR knockout screens to identify host factors critical for these viruses, followed by targeted knockdown screens in vector cells to further characterize viral mechanisms and explore potential antiviral targets. He also develops new tools to study virus-vector cell interactions, with a particular emphasis on ticks.

Research Assistant Professor William M. Schneider leads efforts to investigate replication mechanisms of HBV, a small DNA virus that causes cirrhosis and liver cancer, and LINE-1, an endogenous retroelement active in the human genome. In recent and ongoing work, the team developed new cell culture methods to study HBV and has employed CRISPR and deep mutational scanning technologies to research HBV and LINE-1 replication and identify critical host interactions.

Rice is a faculty member in the David Rockefeller Graduate Program, the Tri-Institutional M.D.-Ph.D. Program, the WCM Graduate Program in Physiology, Biophysics and Systems Biology, and the Tri-Institutional Ph.D. Program in Computational Biology & Medicine.