George M. Shaw, M.D., Ph.D.
George M. Shaw, M.D., Ph.D.
Professor of Medicine
Department: Medicine
Graduate Group Affiliations
Contact information
Perelman School of Medicine
University of Pennsylvania
409 Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104
University of Pennsylvania
409 Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104
Office: 215-746-8514
Fax: 215-573-8976
Fax: 215-573-8976
Email:
shawg@upenn.edu
shawg@upenn.edu
Education:
B.A.
Dartmouth College, 1975.
Ph.D. (Pharmacology)
The Ohio State University, 1979.
M.D.
The Ohio State University, 1980.
Permanent linkB.A.
Dartmouth College, 1975.
Ph.D. (Pharmacology)
The Ohio State University, 1979.
M.D.
The Ohio State University, 1980.
Description of Research Expertise
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 Lab
Current members of the Shaw lab, with the month and the year they joined the lab, and a brief description of their projects (updated summer 2011):
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:
Ranjit Warrier, Ph.D. (07/10) Molecular analysis of SIV transmission and vaccine prevention.
Graduate Students:
Rui Kong (05/07) Neutralization of HIV-2 in vitro and in vivo.
Joshua Baalwa, M.D. (08/07) Molecular pathogenesis of HIV-1 clade A, C and D viruses.
Michael Lopker (09/09) Molecular pathogenesis of transmitted/founder SIVsmE660 and SIVmac251 viruses.
Mark Stoddard (09/10) Molecular identification and pathogenesis of transmitted/founder hepatitis C viruses.
Lab Manager:
Erica Parrish (10/10) HIV/SIV biology; BSL 2+ tissue culture core facility.
Selected Publications
Wu X, C Wang, S O’Dell, Y Li, BF Keele, Z Yang, H Imamichi, N Doria-Rose, JA Hoxie, M Connors, GM Shaw, RT Wyatt and JR Mascola: Selection pressure on HIV-1 envelope by broadly neutralizing antibodies to the conserved CD4-binding site. J Virol 86(10): 5844-56, May 2012.Pandrea I, NF Parish, K Raehtz, T Gaufin, HJ Barbian, D Ma, J Kristoff, R Gautam, F Zhong, GS Haret-Richter, A Trichel, GM Shaw, BH Hahn and C Apetrei: Mucosal simian immunodeficiency virus transmission in African green monkeys: susceptibility to infection is proportional to target cell availability at mucosal sites. J Virol 86(8): 4158-68, Apr 2012.
Ochsenbauer C, TG Edmonds, H Ding, BF Keele, J Decker, MG Salazar, JF Salazar-Gonzalez, R Shattock, BF Haynes, GM Shaw, BH Hahn and JC Kappes: Generation of transmitted/founder HIV-1 infectious molecular clones and characterization of their replication capacity in CD4 T lymphocytes and monocyte-derived macrophages. J Virol 86(5): 2715-28, Mar 2012.
Kong R, H Li, F Bibollet-Ruche, JM Decker, NN Zheng, GS Gottlieb, NB Kiviat, PS Sow, I Georgiev, BH Hahn, PD Kwong, JE Robinson and GM Shaw: Broad and potent neutralizing antibody responses elicited in natural HIV-2 infection. J Virol 86(2): 947-60, Jan 2012.
Tomaras GD, JM Binley, ES Gray, ET Crooks, K Osawa, PL Moore, N Tumba, T Tong, X Shen, NL Yates, J Decker, CK Wibmer, F Gao, SM Alam, P Easterbrook, S Adbool-Karim, G Kamanga, JA Crump, M Cohen, GM Shaw, JR Mascola, BF Haynes, DC Montefiori and L Morris: Polyclonal B cell responses to conserved neutralization epitopes in a subset of HIV-1-infected individuals. J Virol 85(21): 11502-19, Nov 2011.
Ganusov VV, N Goonetilleke, MK Liu, G Ferrari, GM Shaw, AJ McMichael, P Borrow, BT Korber and AS Perelson: Fitness costs and diversity of the cytotoxic T lymphocyte (CTL) response determine the rate of CTL escape during acute and chronic phases of HIV infection. J Virol 85(20): 10518-28, Oct 2011.
Liao HX, X Chen, S Munshaw, R Zhang, DJ Marshall, N Vandergrift, JF Whitesides, X Lu, JS Yu, KK Hwang, F Gao, M Markowitz, SL Heath, KJ Bar, PA Goepfert, DC Montefiori, GM Shaw, SM Alam, DM Margolis, TN Denny, SD Boyd, E Marshal, M Egholm, BB Simen, B Hanczaruk, AZ Fire, G Voss, G Kelsoe, GD Tomaras, MA Moody, TB Kepler and BF Haynes: Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated. J Exp Med 208: 2237-49, Oct 2011.
Jiang C, NF Parrish, CB Wilen, H Li, Y Chen, JW Pavlicek, A Berg, X Lu, H Song, JC Tilton, JM Pfaff, EA Henning, JM Decker, MA Moody, MS Drinker, R Schutte, S Freel, GD Tomaras, R Nedellec, DE Mosier, BF Haynes, GM Shaw, BH Hahn, RW Doms and F Gao: Primary infection by a human immunodeficiency virus with atypical coreceptor tropism. J Virol 85(20): 10669-81, Oct 2011.
Bonsignori M, KK Hwang, X Chen, CY Tsao, L Morris, E Gray, DJ Marshall, JA Crump, SH Kapiga, NE Sam, F Sinangil, M Pancera, Y Yongping, B Zhang, J Zhu, PD Kwong, S O’Dell, JR Mascola, L Wu, GJ Nabel, S Phogat, MS Seaman, JF Whitesides, MA Moody, G Kelsoe, X Yang, J Sodroski, GM Shaw, DC Montefiori, TB Kepler, GD Tomaras, SM Alam, HX Liao and BF Haynes: Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors. J Virol 85(19): 9998-10009, Oct 2011.
Rudicell RS, AK Piel, F Stewart, DL Moore, GH Learn, Y Li, J Takehisa, L Pintea, GM Shaw, J Moore, PM Sharp and BH Hahn: High prevalence of simian immunodeficiency virus infection in a community of savanna chimpanzees. J Virol 85(19): 9918-28, Oct 2011.