Photo of Priscilla L. Yang,  PhD

Priscilla L. Yang, PhD

Harvard Medical School

Harvard Medical School

Priscilla L. Yang, PhD

Harvard Medical School

EDUCATIONAL TITLES

  • Associate Professor, Microbiology and Immunobiology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

My research group is focused equally on basic and applied research goals. First, we are basic scientists studying the molecular mechanisms whereby viruses replicate themselves and cause disease. Second, we use our understanding of molecular mechanism to discover and validate novel antiviral targets and approaches that can complement traditional antiviral drug discovery efforts. While my laboratory is grounded primarily in the study of dengue virus and hepatitis B and C viruses (HBV, HCV), we also investigate the applicability of our inhibitors and antiviral strategies to other viral pathogens. As a chemist and virologist, I have prioritized opportunities in which chemical tools can be used to investigate questions that have not been accessible using more conventional virological methods. This has included 1) the use of novel screening and profiling platforms to identify host factors with functions in dengue virus replication; 2) the use of medicinal chemistry to develop small molecules as mechanistic probes of dengue virus entry, translation, genome replication, and assembly and tool compounds for pharmacological validation of antiviral targets in vitro and in vivo; 3) the use of chemoproteomic profiling methods to identify virus-induced changes in host protein function (rather than host gene expression); and 4) the use of analytical and biophysical chemistry approaches to study the relationship between specific lipid structure and function in viral processes, using hepatitis B and C viruses as models.

Publications

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  • Villareal VA, Fu D, Costello DA, Xie XS, Yang PL. Hepatitis C Virus Selectively Alters the Intracellular Localization of Desmosterol. ACS Chem Biol 2016. PubMed
  • Carocci M, Yang PL. Lactimidomycin is a broad-spectrum inhibitor of dengue and other RNA viruses. Antiviral Res 2016; 128:57-62. PubMed
  • Chou YY, Cuevas C, Carocci M, Stubbs SH, Ma M, Cureton DK, Chao L, Evesson F, He K, Yang PL, Whelan SP, Ross SR, Kirchhausen T, Gaudin R. Identification and characterization of a novel broad spectrum virus entry inhibitor. J Virol 2016. PubMed
  • Villareal VA, Rodgers MA, Costello DA, Yang PL. Targeting host lipid synthesis and metabolism to inhibit dengue and hepatitis C viruses. Antiviral Res 2015; 124:110-121. PubMed
  • Inci F, Filippini C, Baday M, Ozen MO, Calamak S, Durmus NG, Wang S, Hanhauser E, Hobbs KS, Juillard F, Kuang PP, Vetter ML, Carocci M, Yamamoto HS, Takagi Y, Yildiz UH, Akin D, Wesemann DR, Singhal A, Yang PL, Nibert ML, Fichorova RN, Lau DT, Henrich TJ, Kaye KM, Schachter SC, Kuritzkes DR, Steinmetz LM, Gambhir SS, Davis RW, Demirci U. Multitarget, quantitative nanoplasmonic electrical field-enhanced resonating device (NE2RD) for diagnostics. Proc Natl Acad Sci U S A 2015; 112:E4354-63. PubMed
  • Carocci M, Hinshaw SM, Rodgers MA, Villareal V, Burri DJ, Pilankatta R, Maharaj N, Gack MU, Stavale EJ, Warfield KL, Yang PL. The Bioactive Lipid 4-Hydroxyphenyl Retinamide Inhibits Flavivirus Replication. Antimicrob Agents Chemother 2014. PubMed
  • Vetter ML, Zhang Z, Liu S, Wang J, Cho H, Zhang J, Zhang W, Gray NS, Yang PL. Fluorescent visualization of Src by using dasatinib-BODIPY. Chembiochem 2014; 15:1317-24. PubMed
  • de Wispelaere M, LaCroix AJ, Yang PL. The small molecules AZD0530 and dasatinib inhibit dengue virus RNA replication via Fyn kinase. J Virol 2013. PubMed
  • Vetter ML, Rodgers MA, Patricelli MP, Yang PL. Chemoproteomic profiling identifies changes in DNA-PK as markers of early dengue virus infection. ACS Chem Biol 2012. PubMed
  • Zhang Z, Kwiatkowski N, Zeng H, Lim SM, Gray NS, Zhang W, Yang PL. Leveraging kinase inhibitors to develop small molecule tools for imaging kinases by fluorescence microscopy. Mol Biosyst 2012; 8:2523-6. PubMed
  • de Wispelaere M, Yang PL. Mutagenesis of the DI/DIII linker in dengue virus envelope protein impairs viral particle assembly. J Virol 2012; 86:7072-83. PubMed
  • Rodgers MA, Villareal VA, Schaefer EA, Peng LF, Corey KE, Chung RT, Yang PL. Lipid metabolite profiling identifies desmosterol metabolism as a new antiviral target for hepatitis C virus. J Am Chem Soc 2012; 134:6896-9. PubMed
  • Schmidt AG, Lee K, Yang PL, Harrison SC. Small-molecule inhibitors of dengue-virus entry. PLoS Pathog. 2012; 8:e1002627. PubMed
  • Schmidt AG, Yang PL, Harrison SC. Peptide Inhibitors of Flavivirus Entry Derived from the E-protein Stem. J Virol 2010; 84:12549-54. PubMed
  • Schmidt AG, Yang PL, Harrison SC. Peptide inhibitors of dengue-virus entry target a late-stage fusion intermediate. PLoS Pathog. 2010; 6:e1000851. PubMed
  • Yang PL, Althage A, Chung J, Maier H, Wieland S, Isogawa M, Chisari FV. Immune effectors required for hepatitis B virus clearance. Proc Natl Acad Sci U S A 2010; 107:798-802. PubMed
  • Sessions OM,Barrows NJ,Souza-Neto JA,Robinson TJ,Hershey CL,Rodgers MA,Ramirez JL,Dimopoulos G,Yang PL,Pearson JL,Garcia-Blanco MA. Discovery of insect and human dengue virus host factors. Nature 2009; 458:1047-50. PubMed
  • Rodgers MA,Saghatelian A,Yang PL. Identification of an overabundant cholesterol precursor in hepatitis B virus replicating cells by untargeted lipid metabolite profiling. J Am Chem Soc 2009; 131:5030-1. PubMed
  • Zhang J,Yang PL,Gray NS. Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer 2008; 9:28-39. PubMed
  • Hwang YC, Chu JJ, Yang PL, Chen W, Yates MV. Rapid identification of inhibitors that interfere with poliovirus replication using a cell-based assay. Antiviral Res 2008; 77:232-6. PubMed
  • Chu JJ, Yang PL. c-Src protein kinase inhibitors block assembly and maturation of dengue virus. Proc Natl Acad Sci U S A 2007; 104:3520-5. PubMed
  • Yang PL, Althage A, Chung J, Chisari FV. Hydrodynamic injection of viral DNA: a mouse model of acute hepatitis B virus infection. Proc Natl Acad Sci U S A 2002; 99:13825-30. PubMed
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