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George M. Shaw, M.D., Ph.D.

George M. Shaw, M.D., Ph.D.

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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
Office: 215-746-8514
Fax: 215-573-8976
B.A. (Honors Biology)
Dartmouth College, 1975.
Ph.D. (Medicine/Immunobiology)
The Ohio State University, 1979.
M.D. (Medicine/Immunology)
The Ohio State University, 1980.
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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

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), February 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(10.1128/mBio.02510-14.), February 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 February 2015.

Yue L, K Pfafferott, J Baalwa, K Conrod, C Dong, R Rong, DT Claiborne, J Prince, J Tang, R Ribeiro, E Cormier, BH Hahn, A Perelson, GM Shaw, E Karita, J Gilmour, P Goepfert, C Derdeyn, S Allen, P Borrow, and E Hunger. : Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients. PLoS Pathogens January 2015.

Asmal M, C Luedemann, CL Lavine, LV. Mach, H Balachandran, C Brinkley, TN Denny, MG Lewis, H Anderson, R Pal, D Sok, K Le, M Pauthner, BH Hahn, GM Shaw, MS Seaman, NL. Letvin, DR Burton, JG Sodroski, BF Haynes, S Santra. : Infection of monkeys by simian-human immunodeficiency viruses with transmitted/founder Clade C HIV-1 envelopes. Virology January 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. PLoS Pathogens Submitted 2015.

Lopker M, GQ Del Prete, JD Estes, H Li, J Easlick, S Wang, JM Decker, M Piatak, K Bar, G Learn, R Pal, DE Weiss, JD Lifson, BH Hahn, GM Shaw and BF Keele. : Transmitted/founder viruses from the SIVsmE660 and SIVmac251 lineages are replication competent in-vivo. 28th Annual Symposium on Nonhuman Primate Models for AIDS. December 2014.

Del Prete GQ, Ailers B, Moldt B, Keele BF, Estes JD, Rodriguez A, Sampias M, Oswald K, Fast R, Trubey CM, Chertova E, Smedley J, LaBranche CC5, Montefiori DC, Burton DR, Shaw GM, Markowitz M, Piatak M Jr, KewalRamani VN, Bieniasz PD, Lifson JD, Hatziioannou T.: Selection of Unadapted, Pathogenic SHIVs Encoding Newly Transmitted HIV-1 Envelope Proteins. Cell Host Microbe 16(3): 412-8, September 2014.

Gao F, M Bonsignori, H-X Liao, A Kumar, S-M Xia, X Lu, F Cai, K-K Hwang, H Song, T Zhou, RM Lynch, SM Alam, MA Moody, G Ferrari, M Berrong, G Kelsoe, GM Shaw, BH Hahn, DC Montefiori, G Kamanga, M Cohen, P Hraber, PD Kwong, BT Korber, JR Mascola, TB Kepler and BF Haynes: Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies. Cell 158(3): 481-91, July 2014.

Sterret S, Edlefsen PT, Learn GH, Haynes BF, Hahn BH, Shaw GM and Bar KJ.: Low multiplicity of HIV-1 infection and no vaccine enhancement in VAX003 injection drug users. Open Forum Infect Dis June 2014.

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Last updated: 06/25/2015
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