Associate Professor of Microbiology and Molecular Genetics
Department of Microbiology and Immunobiology
Harvard Medical School
200 Longwood Ave.
Boston, MA 02115
Lab Size: Between 5 and 10
My group’s focus has been on the study of mammalian viruses that are significant causes of morbidity and mortality in humans, in particular hepatitis B virus (HBV), hepatitis C virus (HCV), and dengue virus. We have been especially interested in using chemical tools to elucidate molecular mechanisms underlying the replication of viral pathogens to pioneer and validate new antiviral targets and strategies. Current themes in my laboratory include the use of small molecules and RNAi as complementary tools to interrogate the role of specific host factors in viral replication; the use of mass spectrometry-based methods to investigate the structure and function of specific lipids in viral replication; the use of activity-based chemoproteomic profiling to characterize virus-induced changes in the host NTPome; exploitation of the host reactive “cysteineome” to develop irreversible, host-targeted antiviral compounds; and the investigation of polypharmacology as a strategy to develop more effective antivirals with higher barriers to resistance.
de Wispelaere, M., LaCroix, A., and Yang, P.L. (2013) The Small Molecules AZD0530 and Dasatinib Inhibit Dengue Virus RNA Replication via Fyn kinase. Journal of Virology, published ahead of print 24 April 2013, doi: 10.1128/JVI.00632-13. PMCID: PMC3700292.
Vetter, M.L., Rodgers, M.A., Patricelli, M.P., and Yang, P.L. (2012) Chemoproteomic Profiling Identifies Changes in DNA-PK as Markers of Early Dengue Virus Infection. ACS Chemical Biology, 7(12):2019-2026. NIHMSID # 410237, PMCID: PMC3528803.
Zhang, Z., Kwiatkowski, N., Zeng, H., Lim, S.M., Gray, N.S., Zhang, W., and Yang, P.L. (2012) Leveraging kinase inhibitors to develop small molecule tools for imaging kinases by fluorescence microscopy. Mol. BioSyst., 8(10):2523-2526. PMCID: PMC3616611. Highlighted by the journal as a HOT Article
de Wispelaere, M. and Yang, P.L. (2012) Mutagenesis of the domain I - domain III linker in the Dengue Virus envelope protein impairs viral particle assembly. Journal of Virology, 86(13):7072-7083. PMCID: PMC3416339.
Rodgers, M.A., Villareal, V.A., Schaefer, E.A., Peng, L.F., Corey, K.E., Chung, R.T., and Yang, P.L. (2012) Lipid metabolite profiling identifies desmosterol metabolism as a new antiviral target for hepatitis C virus. Journal of the American Chemical Society, 134(16):6896-6899. PMCID: PMC3375380.