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

faculty photo
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
Education:
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 the molecular biology and immunopathogenesis of human immunodeficiency virus (HIV-1) and hepatitis C virus (HCV). Previous highlights of this work include the first molecular clones of HIV-1 (Shaw et al., Science 1984); discovery 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/founder 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). We extended the work to simian immunodeficiency virus (SIV) infection of rhesus macaque monkeys (Keele et al., J Exp Med 2009) and HCV infection of humans (Li et al., PLos Pathogens 2012; Li et al., J Virol 2015; Ke et al., PNAS 2018). Most recently, we have developed novel strategies for constructing simian-human immunodeficiency virus (SHIV) chimeras that replicate efficiently in rhesus macaques (Li et al., PNAS 2016; Li et al., J Virol 2021) and induce broadly neutralizing antibodies (Roark et al., Science 2021).

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 SHIV transmission, persistence and pathogenesis. This project area aims to develop more relevant SHIV-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 is to gain insights into immunopathogenic mechanisms of virus containment and persistence relevant to vaccine design.

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 Winter 2021):

Research Associate Professor:
Hui Li, M.D. (07/03) HIV, SIV, SHIV and HCV transmission biology and immunopathogenesis.

Research Associates:
Fred Bibollet-Ruche, Ph.D.
(07/98) Molecular evolution and pathogenesis of SIV.
Shuyi Wang, M.D. (06/01) Single genome amplification and sequencing of HIV/SIV/HCV to inform vaccine design.
Jesse Connell, M.S. (7/18) Bioinformatics and computational biology.

Graduate Students:
Ryan Roark
(07/16) Novel SHIV designs for the elicitation of V2 apex targeted broadly neutralizing HIV-1 antibodies.
Daniel Morris (7/19) Novel SHIV designs for the elicitation of CD4 binding site and fusion peptide targeted broadly neutralizing HIV-1 antibodies.
Rumi Habib (07/20) Molecular analysis of Env-Ab coevolution leading to novel immunogen designs to elicit V2 apex broadly neutralizing HIV-1 antibodies.

Lab Manager:
Fang-Hua Lee, Ph.D.
(07/15) HIV/SIV entry and neutralization; preclinical trials of novel HIV immunogens.

Staff:
Rachel Baum, Neha Chohan, Wenge Ding, Christie Dionisos, Jinery Lora, Juliette Rando, Chengyan Zhao.

Selected Publications

Li H, S Wang, R Kong, W Ding, F-H Lee, Z Parker, E Kim, GH Learn, P Hahn, B Policicchio, E Brocca-Cofano, C Deleage, X-P Hao, G-Y Chuang, J Gorman, M Gardner, MG Lewis, T Hatzioannou, S Santra, C Apetrei, I Pandrea, SM Alam, H-X Liao, X Shen, GD Tomaras, M Farzan, E Chertova, BF Keele, JD Estes, JD Lifson, RW Doms, DC Montefiori, BF Haynes, JG Sodroski, PD Kwong, BH Hahn, and GM Shaw.: Envelope residue 375 substitutions in simian-human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques. Proceedings of the National Academy of Sciences of the United States of America 113(24): E3413-22, Jun 2016.

Bonsignori M, EF Kreider, D Fera, RR Meyerhoff, T Bradley, K Wiehe, SM Alam, B Aussedat, WE Walkowicz, K-K Hwang, KO Saunders, R Zhang, MA Gladden, A Monroe, A Kumar, S-M Xia, M Cooper, MK Louder, K McKee, RT Bailer, BW Pier, CA Jette, G Kelsoe, WB Williams, L Morris, J Kappes, K Wagh, G Kamanga, MS Cohen, PT Hraber, DC Montefiori, A Trama, H-X Liao, TB Kepler, MA Moody, F Gao, SJ Danishefsky, JR Mascola, GM Shaw, BH Hahn, SC Harrison, BT Korber, BF Haynes: Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies. Sci. Transl. Med. 9(381): eaai7514, March 2017.

Waugh K, EF Kreider, Y Li, HJ Barbian, GH Learn, E Giorgi, PT Hraber, TG Decker, AG Smith, MV Gondim, L Gillis, J Wandzilak, G-Y Chuang, R Rawi, F Cai, P Pellegrino, I Williams, J Overbaugh, F Gao, PD Kwong, BF Haynes, GM Shaw, P Borrow, MS Seaman, BH Hahn, B Korber: Completeness of the HIV-1 envelope glycan shield at transmission determines neutralization breadth. Cell Reports 25(4): 893-908.e7, 2018.

Ke R, H Li, S Wang, RM Ribeiro, EE Giorgi, T Bhattacharya, RJO Barnard, GM Shaw and AS Perelson: Superinfection and Cure of Infected Cells as Novel Mechanisms Contributing to Rapid Hepatitis C Virus Expansion and Persistence. Proc Natl Acad Sci 115(30): E7139-E7148, 2018.

Pauthner MG, JP Nkolola, C Havenar-Daughton, B Murell, SM Reiss, R Bastidas, J Prevost, R Nedellec, B von Bredow, CA Cottrell, DW Kulp, T Tokatlian, B Nogal, M Bianchi, H Li, JH Lee, ST Butera, DT Evans, L Hangartner, A Finzi, IA Wilson, RT Wyatt, DJ Irvine, WR Schief, AB Ward, RW Sanders, S Crotty, GM Shaw, DH Barouch and DR Burton.: Vaccine-induced protection from homologous tier 2 SHIV challenge in nonhuman primates depends on serum-neutralizing antibody titers. Immunity 50(1): 241-252.e6, January 2019.

Bibollet-Ruche F, RM Russell, L Weimin, GBE Stewart-Jones, S Sherrill-Mix, Y Li, GH Learn, AG Smith, MVP Gondim, LJ Plenderleith, JM Decker, JL Easlick, KS Wetzel, RG Collman, S Ding, A Finzi, A Ayouba, M Peeters, FH Leendertz, J van Schijndel, A Goedmakers, E Ton, C Boesch, H Kuehl, M Arandjelovic, P Dieguez, M Murai, C Colin, K Koops, S Speede, MK Gonder, MN Muller, CM Sanz, DB Morgan, R Atencia, D Cox, AK Piel, FA Stewart, JN Ndjango, D Mjungu, EV Lonsdorf, AE Pusey, PD Kwong, PM Sharp, GM Shaw and BH Hahn.: CD4 receptor diversity in chimpanzees protects against SIV infection. Proc Natl Acad Sci USA 116(8): 3229-3238, February 2019.

Felber BK, Z Lu, X Hu, A Valentin, M Rosati, CAL Remmel, JA Weiner, MC Carpenter, K Faircloth, S Stanfield-Oakley, WB Williams, X Shen, GD Tomaras, CC LaBranche, D Montefiori, HV Trinh, M Rao, MS Alam, NA Vandergrift, KO Saunders, Y Wang, W Rountree, J Das, G Alter, SG Reed, PP Aye, F Schiro, B Pahar, JP Dufor, RS Veazey, PA Marx, DJ Venzon, GM Shaw, G Ferrari, ME Ackerman, BF Haynes, GN Pavlakis: Co-immunization of DNA and Protein in the Same Anatomical Sites Induces Superior Protective Immune Responses against SHIV Challenge. Cell Reports 31(6): 107624, May 2020.

Arunachalam PS, TP Charles, V Joag, SV Bollimpelli, MKD Scott, F Wimmers, SL Burton, CC Labranche, C Petitdemange, S Gangadhara, TM Styles, CF Quarnstrom, KA Walter, TJ Ketas, T Legere, PBJ Reddy, SP Kasturi, A. Tsai, B Yeung, S Gupta, KA Walter, M Tomai, J Vasilakos, GM Shaw, JP Moore, S Subramaniam, P Khatri, D Montefiori, PA Kozlowski, C Derdeyn, E Hunter, D Masopust, RR Amara and B Pulendran: T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers. Nature Medicine 26(6): 932-940, June 2020.

Roark RS, H Li, WB Williams, H Chug, RD Mason, J Gorman, S Wang, F Lee, J Rando, M Bonsignori, K Hwang, KO Sanders, K Wiehe, MA Moody, PT Hraber, K Wagh, EE Giorgi, RM Russell, F Bibollet-Ruche, W Liu, J Connell, AG Smith, J DeVoto, AI Murphy, J Smith, W Ding, C Zhao, N Chohan, M Okumura, C Rosario, Y Ding, E Lindemuth, AM Bauer, KJ Bar, D Ambrozak, CW Chao, G Chuang, H Geng, BC Lin, MK Louder, R Nguyen, B Zhang, MG Lewis, D. Raymond, NA Doria-Rose, CA Schramm, DC Douek, M Roederer, TB Kepler, G Kelsoe, JR Mascola, PD Kwong, BT Korber, SC Harrison, BF Haynes, BH Hahn, GM Shaw: Recapitulation of HIV-1 Env-Antibody Coevolution in Macaques Leading to Neutralization Breadth. Science 371(6625): eabd2628, January 2021.

Li H, S Wang, FH Lee, RS Roark, AI Murphy, J Smith, C Zhao, J Rando, N Chohan, Y Ding, E Kim, E Lindemuth, KJ Bar, I Pandrea, C Apetrei, BF Keele, JD Lifson, MG Lewis, TN Denny, BF Haynes, BH Hahn, GM Shaw: New SHIVs and improved design strategy for modeling HIV-1 transmission, immunopathogenesis, prevention and cure. J Virol (bioRxiv https://doi.org/10.1101/2021.01.13.426578) January 2021.

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Last updated: 03/29/2021
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