Faculty

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

Professor of Medicine (Hematology-Oncology)

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Department: Medicine

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1f Graduate Group Affiliations 8

Cell and Molecular Biology

46 Contact information
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Perelman School of Medicine
22 University of Pennsylvania
1c 409 Johnson Pavilion
35 3610 Hamilton Walk
Philadelphia, PA 19104

2e Office: 215-746-8514
32 Fax: 215-573-8976
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Email:
shawg@pennmedicine.upenn.edu

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13 Education:
21 9 B.A. 1b (Honors Biology) c
2a Dartmouth College, 1975.
21 a Ph.D. 23 (Medicine/Immunobiology) c
32 The Ohio State University, 1979.
21 9 M.D. 20 (Medicine/Immunology) c
32 The Ohio State University, 1980.
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Links
83 Department of Microbiology Faculty Page
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5 3 3 92 Permanent link
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b6 > Perelman School of Medicine > Faculty > Details a

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Description of Research Expertise

5d4 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), serving as a model system for HIV-1 vaccine development.
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3a Current projects in the laboratory include:
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19f 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.
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19b 2. Molecular studies of SHIV-induced broadly neutralizing antibodies (bNAbs). This project area aims to elucidate viral-host interactions underlying the development of bNAbs in SHIV-infected monkeys. The lab focuses on canonical bNAb supersites including V2 apex, V3 glycan, CD4-binding site and fusion peptide. A practical application of this work is in HIV/SIV vaccine design and assessment.
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1b7 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 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.
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26 Members of the Shaw Lab
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9b Current members of the Shaw lab, with the month and the year they joined the lab, and a brief description of their projects (updated Spring 2024):
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2c Research Associate Professor:
7c Hui Li, M.D. (07/03) HIV, SIV, SHIV and HCV transmission biology, immunopathogenesis and vaccine development.
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29 Senior Research Investigators:
8b Fred Bibollet-Ruche, Ph.D. (07/98) Molecular evolution and pathogenesis of SIV; HIV immunopathogenesis and vaccine development.
53 Jesse Connell, M.S. (7/18) Bioinformatics and computational biology.
5b Kasirajan (Nathan) Ayyanathan, Ph.D. (01/24) HIV and SHIV molecular biology.
64 Weimin Liu, M.D. (07/98) HIV, SIV and SHIV immunobiology; origins of HIV and Malaria.
65 Yingying Li, M.D. (07/98) HIV, SIV and SHIV immunobiology; origins of HIV and Malaria.
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1d Graduate Students:
c9 Daniel Morris (7/19) Novel SHIV designs for the elicitation of CD4 binding site and fusion peptide targeted broadly neutralizing HIV-1 antibodies; CD4bs and fusion peptide immunogen design.
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9e Rumi Habib (07/20) Molecular analysis of Env-Ab coevolution leading to V2 apex broadly neutralizing HIV-1 antibodies; V2 apex immunogen design.
89 Michael Hogarty (07/22) Immunobiology of SHIV-infection versus mRNA vaccination targeting the V3 glycan epitope supersite.
6a Ashwin Skelly (07/21) Elicitation of V3 glycan supersite bNAbs; V3 glycan immunogen design.
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17 Lab Manager:
5c Ajay Singh (07/22) SHIV development; preclinical trials of novel HIV immunogens.
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11 Staff:
ae Mary Campion, John Carey, Wenge Ding, Colette Gordon, Emily Lewis, Jinery Lora, Christian Martella, Younghoon Park, Samantha Plante, Kirsten Sowers, Chengyan Zhao.
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Selected Publications

2be 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.

292 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.

1de Wagh 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.

159 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.

248 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.

2cc 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.

284 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.

271 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.

2e8 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 2 37 371(6625): eabd2628, January 2021.

1b0 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 95(11): e00071-21, March 2021.

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