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Priscilla L. Yang, Ph.D.

TitleAssociate Professor of Microbiology and Immunobiology
InstitutionHarvard Medical School
DepartmentMicrobiology and Immunobiology
AddressHarvard Medical School
MBIB, Room 930 D
77 Avenue Louis Pasteur
Boston MA 02115
Phone617/432-5415
Fax617/432-5418

 Overview 
 overview
The focus of my research group is 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 (DENV). I have been especially interested in the development of a variety of chemical tools to characterize novel interactions between viral pathogens and their hosts at both the molecular and pathway levels.

First, I have led successful efforts in developing and using immunofluorescence image-based screens to identify both small molecules and shRNAs that perturb dengue virus replication. As we follow-up on our original kinase inhibitor screens, a significant portion of my group is currently focused on the characterization of the mechanisms by which Src, Abl, and other specific kinases regulate the dengue virus replication cycle.

Second, my group has developed small molecule inhibitors of dengue virus entry and used these as mechanistic probes in cellular and biochemical studies of the dengue virus entry. We have discovered inhibitors that can simultaneously inhibit two different steps of the dengue virus replication cycle through interactions with two distinct targets, one a host kinase and the other the envelope protein coating the virion surface.

Third, my group has developed global liquid chromatography - mass spectrometry based profiling as a way to identify host lipids and lipid metabolic pathways that are important for the replication of viral pathogens. In our initial work, we have focused on profiling HBV and HCV, two phylogenetically unrelated viruses that cause chronic infections in the liver. This work has led to the identification of virus-specific perturbations in sterol metabolism that promote viral replication. My group is actively investigating the mechanisms responsible for these perturbations as well as their biological significance in the viral life cycle and pathogenesis. In addition, we are performing comparative lipid metabolite profiling of additional viral pathogens to identify common pathways utilized by viruses that cause chronic versus acute infections and viruses that infect the liver versus those that infect other cells and tissues.

The members of my group come from diverse backgrounds including chemistry, biochemistry, cell biology, and virology. My group has the chemical and virological expertise as well as the instrumentation, collaborations, and institutional support to use these tools to study the basic virology and pathogenesis of these human viral pathogens. Our work with hepatitis B and C viruses as well as our work using small molecules to interrogate the signal transduction pathways of host protein kinases are geared towards understanding the role of viral pathogens in cancer biology.


 Mentoring 
 completed student projects
Creating an in vivo Murine Model of Hepatitis C Virus Through Directed Evolution
Summer, 06/20/05 - 08/19/05
Creating a mouse model for Hepatitis C Virus (HCV) using a chemical selection
Summer, 06/01/06 - 09/01/05

 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
List All   |   Timeline
  1. de Wispelaere M, Lacroix AJ, Yang PL. The Small Molecules AZD0530 and Dasatinib Inhibit Dengue Virus RNA Replication via Fyn Kinase. J Virol. 2013 Jul; 87(13):7367-81.
    View in: PubMed
  2. 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 Dec 21; 7(12):2019-26.
    View in: PubMed
  3. 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 Oct; 8(10):2523-6.
    View in: PubMed
  4. de Wispelaere M, Yang PL. Mutagenesis of the DI/DIII linker in dengue virus envelope protein impairs viral particle assembly. J Virol. 2012 Jul; 86(13):7072-83.
    View in: PubMed
  5. 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 Apr 25; 134(16):6896-9.
    View in: PubMed
  6. Schmidt AG, Lee K, Yang PL, Harrison SC. Small-molecule inhibitors of dengue-virus entry. PLoS Pathog. 2012; 8(4):e1002627.
    View in: PubMed
  7. Yang PL, Gao M, Lin K, Liu Q, Villareal VA. Anti-HCV drugs in the pipeline. Curr Opin Virol. 2011 Dec; 1(6):607-16.
    View in: PubMed
  8. Schmidt AG, Yang PL, Harrison SC. Peptide inhibitors of flavivirus entry derived from the E protein stem. J Virol. 2010 Dec; 84(24):12549-54.
    View in: PubMed
  9. Schmidt AG, Yang PL, Harrison SC. Peptide inhibitors of dengue-virus entry target a late-stage fusion intermediate. PLoS Pathog. 2010 Apr; 6(4):e1000851.
    View in: PubMed
  10. 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 Jan 12; 107(2):798-802.
    View in: PubMed
  11. 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 Apr 23; 458(7241):1047-50.
    View in: PubMed
  12. 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 Apr 15; 131(14):5030-1.
    View in: PubMed
  13. Zhang J, Yang PL, Gray NS. Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer. 2009 Jan; 9(1):28-39.
    View in: PubMed
  14. 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 Mar; 77(3):232-6.
    View in: PubMed
  15. Chu JJ, Yang PL. c-Src protein kinase inhibitors block assembly and maturation of dengue virus. Proc Natl Acad Sci U S A. 2007 Feb 27; 104(9):3520-5.
    View in: PubMed
  16. 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 Oct 15; 99(21):13825-30.
    View in: PubMed
  17. Gildersleeve J, Janes J, Ulrich H, Yang P, Barbas C, Schultz PG. Development of a genetic selection for catalytic antibodies. Bioorg Med Chem Lett. 2002 Jun 17; 12(12):1691-4.
    View in: PubMed
  18. P.L. Yang, A. Althage, J.S. Chung, F.V. Chisari. Hydrodynamic transfection: a new model for acute hepatitis B virus infection. Proc Natl Acad Sci USA. 2002; 99(21):13825-13830.
  19. Yin J, Mundorff EC, Yang PL, Wendt KU, Hanway D, Stevens RC, Schultz PG. A comparative analysis of the immunological evolution of antibody 28B4. Biochemistry. 2001 Sep 11; 40(36):10764-73.
    View in: PubMed
  20. Yang PL, Schultz PG. Mutational analysis of the affinity maturation of antibody 48G7. J Mol Biol. 1999 Dec 17; 294(5):1191-201.
    View in: PubMed
  21. Priscilla Li-Ning Yang, Ph.D. Structure, Function, and Evolution of Catalytic Antibodies [dissertation]. 1999.
  22. P.A. Patten, N.S. Gray, P.L. Yang, C.B. Marks, G. J. Wedemayer, J.J. Boniface, R.C. Stevens, P.G. Schultz. The immunological evolution of catalysis. Science (Washington D C). 1996; 271(5252):1086-1091.
  23. Ulrich HD, Patten PA, Yang PL, Romesberg FE, Schultz PG. Expression studies of catalytic antibodies. Proc Natl Acad Sci U S A. 1995 Dec 5; 92(25):11907-11.
    View in: PubMed
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