Richard Wyatt, PhD
Scripps Research Joint Appointments
Research Focus
HIV-1 Envelope Glycoprotein Structure and Immunogenicity
The human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of AIDS causing a huge toll of human malaise and morbidity. Although a substantial arsenal of drugs can treat this devastating disease, a broadly effective vaccine remains the most cost-effective way to halt further spread of this virus in the human population. However, due to the approximately 32 million infected individuals already infected in the human population world-wide, and the incredible diversity of this virus in the individual and the population, such a vaccine has proven difficult to develop. Because most viral vaccines protect against disease by neutralizing antibodies, we study the HIV-1 envelope glycoproteins (Env) as antigens, as immunogens and at the atomic level of structural refinement to gain insight in how to better elicit antibodies directed against these external, variable and heavily glycosylated neutralizing determinants. We make specialized Env variants and analyze their biochemical and biophysical features, use them as probes to isolate new and novel broadly neutralizing antibodies and assess their immunogenicity all as part of the plan to better elicit neutralizing antibodies by rational, structure-guided vaccine design.
Education
Ph.D. (Immunology), Tufts University, School of Medicine, 1991M.S. (Biology), Southern Connecticut State University, 1982
B.S. (Biology), Trinity College, 1974
Professional Experience
2009-2017 Professor of Immunology, Immunology and Microbial Science (IMS), Scripps Research2007-2009 Senior Investigator (tenure), Chief, Structural Virology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
2001-2006 Investigator, Chief, Structural Virology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
1999-2000 Instructor, Department of Medicine, Harvard Medical School, Harvard University
1997-2000 Instructor, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute
1994-1999 Instructor, Department of Pathology, Harvard Medical School, Harvard University
1994-1997 Instructor, Division of Human Retrovirology, Dana-Farber Cancer Institute
1991-1994 Research Fellow, Department of Pathology, Dana-Farber Cancer Institute
1991-1994 Research Fellow, Division of Human Retrovirology, Dana-Farber Cancer Institute
1991-1993 Research Fellow, NIAID AIDS Postdoctoral Training Grant, Dana-Farber Cancer Institute
Awards & Professional Activities
1998-present: Member of the American Foundation for AIDS Research (AmFAR) Scientific Advisory Committee 1998 - Presenter to the Dana-Farber Cancer Institute Scientific Advisory Board 2006 - 2009 Member – NIAID Promotion and Tenure Title 42 Sub Committee 1996 - present: Member of the American Association for the Advancement of Science 2000 - present: Member of the American Microbiology Association 2000 -present: Charter member of the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Consortium (NAC)Editorial Board
2005 - present: Journal of Virology 2002 - present: Aids Fonds Grant Applications, Netherlands
Selected References
Guenaga J, Garces F, de Val N, Stanfield RL, Dubrovskaya V, Higgins B, Carrette B, Ward AB, Wilson IA, Wyatt RT. Glycine Substitution at Helix-to-Coil Transitions Facilitates the Structural Determination of a Stabilized Subtype C HIV Envelope Glycoprotein. Immunity. 2017 May 16;46(5):792-803.e3. doi:10.1016/j.immuni.2017.04.014. PMID: 28514686
Martinez-Murillo P, Tran K, Guenaga J, Lindgren G, Àdori M, Feng Y, Phad GE, Vázquez Bernat N, Bale S, Ingale J, Dubrovskaya V, O'Dell S, Pramanik L, Spångberg M, Corcoran M, Loré K, Mascola JR, Wyatt RT, Karlsson Hedestam GB. Particulate Array of Well-Ordered HIV Clade C Env Trimers Elicits Neutralizing Antibodies that Display a Unique V2 Cap Approach. Immunity. 2017 May 16;46(5):804-817.e7. doi:10.1016/j.immuni.2017.04.021. PMID: 28514687
Dubrovskaya V, Guenaga J, de Val N, Wilson R, Feng Y, Movsesyan A, Karlsson Hedestam GB, Ward AB, Wyatt RT. Targeted N-glycan deletion at the receptor-binding site retains HIV Env NFL trimer integrity and accelerates the elicited antibody response. PLoS Pathog. 2017 Sep 13;13(9):e1006614. doi: 10.1371/journal.ppat.1006614. PMID: 28902916
Bale S, Martiné A, Wilson R, Behrens AJ, Le Fourn V, de Val N, Sharma SK, Tran K, Torres JL, Girod PA, Ward AB, Crispin M, Wyatt RT. Cleavage-Independent HIV-1 Trimers From CHO Cell Lines Elicit Robust Autologous Tier 2 Neutralizing Antibodies. Front Immunol. 2018 May 24;9:1116. doi: 10.3389/fimmu.2018.01116. PMID: 29881382