Professional Snapshot
Administrative Appointments
- Member of School of Medicine Awards Committee, Stanford University School of Medicine (2005 - present)
- Member of the Committee on Graduate Studies, Stanford University (2001 - 2004)
- Director of Graduate Program, Dept. Microbiology and Immunology, Stanford University School of Medicine (2002 - present)
Honors and Awards
- Editor, Virology (2003-present)
- The Sidney and Skippy Frank Prize, Institute for Immunity, Transplantation and Infection, Stanford University (2006)
- Faculty Research Award, American Cancer Society (1992-1997)
- Postdoctoral Fellowship, Deutsche Forschungsgemeinschaft (1982-1985)
- Predoctoral Fellowship, Studienstiftung des Deutschen Volkes (1979-1982)
Professional Education
| Ph.D.: | SUNY at Stony Brook, Molecular Virology (1982) |
| B.S.: | University of Konstanz, Molecular Genetics (1979) |
Postdoctoral Advisees
Teresa Abraham, Cara Belsham, Gabriele Fuchs, Kara Lee Norman, Selena Sagan
Graduate & Fellowship Program Affiliations
Web Site Links
Industry Relationships
Stanford is committed to ethical and transparent interactions with our industry partners. It is our policy to disclose payments of $5,000 or more, equity valued at $5,000 or more in a publicly traded company, or any equity in a privately held company, to physicians and scientists employed by Stanford University from companies or other commercial entities with which they interact as part of their professional activities. View Full Information
| Consulting: | Merck/siRNA |
Scientific Focus
Research Interests
Our laboratory has been been studying the mechanism by which a liver-specific microRNA, miR-122, regulates the amplification of the hepatitis C virus (HCV) genome in cultured cells. Specifically, we have found that miR-122 interacts with the 5' end of the viral RNA and is essential for viral replication. Consequently, sequestration of miR-122 by antisense-oligonucleotides results in rapid loss of viral RNA. We are currently examining the mechanism by which miR-122 helps HCV RNA replication and are searching for cellular targets of miR-122 and their regulation by miR-122. These lines of investigations will lead to new insights how these small noncoding RNAs regulate expression of cellular and viral mRNAs and may point to new venues for antiviral therapeutics against HCV.
In a second line of investigation, we are studying the unusual mechanism of translation initiation by internal ribosome entry in certain viral (i.e. HCV, picornavirsues and some insect viruses) and cellular mRNA molecules. In the conventional scanning mechanism of translation initiation, which operates on most mRNA molecules, 40S subunits are recruited at or near the 5' end of the mRNA. Subsequently, the 40S ribosomal subunits are predicted to scan the mRNA in a 5' to 3' direction until the first AUG codon is encountered as start site for protein synthesis. However, certain viral and cellular mRNAs, notably encoding proto-oncogenes and regulatory genes, contain long 5' noncoding regions with multiple AUG codons. Thus, the translation initiation rate in these mRNAs is predicted to be low according to the scanning model; alternatively, other translation initiation mechanisms may operate to ensure efficient translation. Indeed, some of such mRNAs with long leaders contain internal ribosome entry sites which can bind ribosomes directly. Much of our work has been focussing on the mechanism and prevalence of internal ribosome binding. Specifically, we are addressing the following questions: Which...
Publications
- Modulation of Hepatitis C virus RNA abundance and the isoprenoid biosynthesis pathway by microRNA miR-122 involves distinct mechanisms. J Virol. 2009
- Temperature protects insect cells from infection by cricket paralysis virus. J Virol. 2009
- The Imd pathway is involved in antiviral immune responses in Drosophila. PLoS One. 2009; (10): e7436
- Biological basis for restriction of microRNA targets to the 3' untranslated region in mammalian mRNAs. Nat Struct Mol Biol. 2009; (2): 144-50
- Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. Cell Host Microbe. 2008; (1): 77-85
