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My laboratory has a longstanding interest in human and simian immunodeficiency virus (HIV/SIV) molecular biology and pathogenesis and hepatitis C virus (HCV). Previous highlights of this work include the first molecular clones of HIV-1 (Shaw et al., Science 1984); recognition of the quasispecies nature of HIV-1 in vivo (Saag et al., Nature 1988); discovery of the dynamic and persistent nature of viral replication in vivo (Clark et al., N Engl J Med 1991; Piatak et al., Science 1993; Wei et al., Nature 1995); mechanisms of virus persistence in the face of evolving cellular and humoral immune responses (Borrow et al., Nature Medicine 1997; Wei et al., Nature 2003); and molecular identification and biological characterization of transmitted HIV-1 genomes and their progeny (Keele et al., Proc Natl Acad Sci USA 2008; Salazar et al., J Exp Med 2009; Li et al., PLoS Pathogens 2010). More recently, we have extended the work to SIV infection of rhesus macaque monkeys (Keele et al., J Exp Med 2009) and HCV infection of humans (Li et al., CROI 2011).Current projects in the laboratory include:1. Molecular studies of HIV-1 transmission, persistence and pathogenesis. This project area includes a molecular and biological analysis of HIV-1 viruses responsible for transmission and productive clinical infection resulting from heterosexual, homosexual and intravenous exposures and their subsequent evolution. The long-range goal is to develop effective vaccine strategies to prevent infection.2. Molecular studies of SIV transmission, persistence and pathogenesis. This project area aims to develop more relevant SIV-rhesus macaque mucosal infection models and a clearer understanding of viral-host events responsible for transmission and productive clinical infection. A practical application of this work is in HIV/SIV vaccine design and assessment.3. Molecular studies of HCV transmission, persistence and pathogenesis. This project area aims to leverage our recent discoveries in HIV-1 and SIV transmission biology based on single genome amplification and sequencing of plasma virion RNA to elucidate HCV transmission and early virus evolution. A major goal of this work will be to gain insights into immunopathogenic mechanisms of virus containment and persistence relevant to therapeutics and vaccine design. A second major goal is the development of novel strategies for identifying and characterizing full-length infectious molecular clones of HCV representing the seven major pandemic genotypes for use in in vitro and in vivo modeling and analyses.Members of the Shaw LabCurrent members of the Shaw lab, with the month and the year they joined the lab, and a brief description of their projects (updated Summer 2016):Research Assistant Professors:Fred Bibollet-Ruche, Ph.D. (07/98) Molecular evolution and pathogenesis of SIV.Hui Li, M.D. (07/03) HIV, SIV and hepatitis C virus transmission biology and pathogenesis.Research Associate:Shuyi Wang, M.D. (06/01) Single genome amplification and sequencing of HIV/SIV/HCV.Post-doctoral Research Fellow:Muhammad Nauman Zahid (08/16) Graduate Students:Ryan Roark (07/16) SHIV design for the elicitation of broadly neutralizing antibodies and HIV/SHIV-antibody co-evolution.Lab Manager:Fang-Hua Lee, Ph.D. (07/15) HIV/SIV entry and neutralization.
Kell A, Stoddard M, Li H, Marcotrigiano J, Shaw GM, Gale M Jr.: Pathogen-Associated Molecular Pattern Recognition of Hepatitis C Virus Transmitted/Founder Variants by RIG-I Is Dependent on U-Core Length. Journal of Virology 89 (21): 11056-68.,2015.
Hui Li, Mark Stoddard, Shuyi Wang, Elena Giorgi, Lily Blair, Gerald Learn, Beatrice Hahn, Harvey J Alter, Michael Busch, Daniel Fierer, Ruy Ribeiro, Alan Perelson, Tanmoy Bhattacharya, and George Shaw: Single Genome Sequencing of Hepatitis C Virus in Donor-Recipient Pairs Distinguishes Modes and Models of Virus Transmission and Early Diversification Journal of Virology : 02156-15,2015.
Hraber P, B Korber, K Wagh, EE Giorgi, T Bhattacharya, S Gnanakaran, AS Lapedes, GH Learn, E Kreider, Y Li, GM Shaw, BH Hahn, DC Montefiori, SM Alam, M Bonsignori, MA Moody, H-X Liao, F Gao, BF Haynes.: Longitudinal Antigenic Sequences and Sites from Intrahost Evolution (LASSIE) Identifies Immune-Selected HIV Variants over Time. Viruses 7 (10): 5443-5475,2015.
Moody MA, Gao F, Gurley TC, Amos JD, Kumar A, Hora B, Marshall DJ, Whitesides JF, Xia SM, Parks R, Lloyd KE, Hwang KK, Lu X, Bonsignori M, Finzi A, Vandergrift NA, Alam SM, Ferrari G, Shen X, Tomaras GD, Kamanga G, Cohen MS, Sam NE, Kapiga S, Gray ES, Tumba NL, Morris L, Zolla-Pazner S, Gorny MK, Mascola JR, Hahn BH, Shaw GM, Sodroski JG, Liao HX, Montefiori DC, Hraber PT, Korber BT, Haynes BF.: Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses. Cell Host Microbe 18 (3): 354-62,2015.
Santra S, Tomaras GD, Warrier R, Nicely NI, Liao HX, Pollara J, Liu P, Alam SM, Zhang R, Cocklin SL, Shen X, Duffy R, Xia SM, Schutte RJ, Pemble Iv CW, Dennison SM, Li H, Chao A, Vidnovic K, Evans A, Klein K, Kumar A, Robinson J, Landucci G, Forthal DN, Montefiori DC, Kaewkungwal J, Nitayaphan S, Pitisuttithum P, Rerks-Ngarm S, Robb ML, Michael NL, Kim JH, Soderberg KA, Giorgi EE, Blair L, Korber BT, Moog C, Shattock RJ, Letvin NL, Schmitz JE, Moody MA, Gao F, Ferrari G, Shaw GM, Haynes BF.: Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques. PLoS Pathogen 11 (8): e1005042,2015.
Barbian HJ, Decker JM, Bibollet-Ruche F, Galimidi RP, West AP Jr, Learn GH, Parrish NF, Iyer SS, Li Y, Pace CS, Song R, Huang Y, Denny TN, Mouquet H, Martin L, Acharya P, Zhang B, Kwong PD, Mascola JR, Verrips CT, Strokappe NM, Rutten L, McCoy LE, Weiss RA, Brown CS, Jackson R, Silvestri G, Connors M, Burton DR, Shaw GM, Nussenzweig MC, Bjorkman PJ, Ho DD, Farzan M, Hahn BH.: Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas. mBio 6 (2): e00296-15,2015.
Stoddard MB, H Li, S Wang, M Saeed, L Andrus, W Ding, X Jiang, GH Learn, M von Schaewen, J Wen, PA Goepfert, BH Hahn, A Ploss, CM Rice, GM Shaw.: Identification, molecular cloning, and analysis of full-length hepatitis C virus transmitted/founder genotypes 1, 3, and 4. mBio 6 (2): e02518-14,2015.
Mitchell AM, AEL Stone, L Cheng, K Ballinger, MG Edards, M Stoddard, H Li, L Golden-Mason, GM Shaw, S Khetani, HR Rosen.: Transmitter/founder hepatitis C viruses induce cell type- and genotype-specific differences in innate signaling within the liver. mBio 6 (2): e02510-14,2015.
Giugliano S, M Kriss, L Golden-Mason, E Dobrinskikh, AEL Stone, A Soto-Gutierrez, A Mitchell, SR Khetani, D Yamane, M Stoddard, H Li, GM Shaw, MG Edwards, SM Lemon, M Gale, VH Shah, HR Rosen.: Hepatitis C Virus Infection Induces Autocrine Interferon Signaling by Human Liver Endothelial Cells and Release of Exosomes, Which Inhibits Viral Replication. Gastroenterology 148 (2): 392-402,2015.
Perelman School of MedicineUniversity of Pennsylvania409 Johnson Pavilion3610 Hamilton Walk