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), serving as a model system for HIV-1 vaccine development.

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-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.

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.

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 Spring 2024):

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

Senior Research Investigators:
Fred Bibollet-Ruche, Ph.D. (07/98) Molecular evolution and pathogenesis of SIV; HIV immunopathogenesis and vaccine development.
Jesse Connell, M.S. (7/18) Bioinformatics and computational biology.
Kasirajan (Nathan) Ayyanathan, Ph.D. (01/24) HIV and SHIV molecular biology.
Weimin Liu, M.D. (07/98) HIV, SIV and SHIV immunobiology; origins of HIV and Malaria.
Yingying Li, M.D. (07/98) HIV, SIV and SHIV immunobiology; origins of HIV and Malaria.

Graduate Students:
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.

Rumi Habib (07/20) Molecular analysis of Env-Ab coevolution leading to V2 apex broadly neutralizing HIV-1 antibodies; V2 apex immunogen design.
Michael Hogarty (07/22) Immunobiology of SHIV-infection versus mRNA vaccination targeting the V3 glycan epitope supersite.
Ashwin Skelly (07/21) Elicitation of V3 glycan supersite bNAbs; V3 glycan immunogen design.


Lab Manager:
Ajay Singh (07/22) SHIV development; preclinical trials of novel HIV immunogens.

Staff:
Mary Campion, John Carey, Wenge Ding, Colette Gordon, Emily Lewis, Jinery Lora, Christian Martella, Younghoon Park, Samantha Plante, Kirsten Sowers, 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): E3413-22,2016.

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): eaai7514,2017.

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.

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.e6,2019.

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): 3229-3238,2019.

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): 107624,2020.

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): 932-940,2020.

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): eabd2628,2021.

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 95 (11): e00071-21,2021.

Academic Contact Information

Perelman School of Medicine
University of Pennsylvania
409 Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104
Phone: 215-746-8514