Immunology Faculty Member - Bruce Walker, MD

Bruce Walker, MD

Director, Ragon Institute of MGH, MIT and Harvard
Professor of Medicine, Harvard University
Investigator, Howard Hughes Medical Institute


Ragon Institute of MGH, MIT and Harvard
400 Technology Square, Room 870

Cambridge, MA 02139
Tel: 857-268-7072
Fax: 857-268-7142
Email: bwalker@mgh.harvard.edu



Dr. Bruce Walker is the Director of the Ragon Institute of MGH, MIT and Harvard, a Professor of Medicine at Harvard Medical School, and a Howard Hughes Medical Institute Investigator. A physician-scientist board-certified in Infectious Disease, his research focuses on cellular immune responses in chronic viral infections, with a particular focus on HIV and human immunology. Currently the lab is focused on understanding durable immune control of HIV in unique clinical cohorts, integrating studies of host genetics, adaptive immune responses and virology. This includes studies utilizing an extensive cohort of persons who control HIV infection without the need for medication. These so-called “elite controllers” maintain undetectable viral loads and normal CD4+ T cell counts in the absence of antiretroviral therapy. Genetic studies performing a genome wide association study of persons revealed that amino acids lining the HLA class I binding groove modulate host control of HIV, accounting for approximately 20% of variability observed. These studies implicated class I restricted CD8+ T cells in modulating control, which we have shown is due in part to fitness-impairing mutations that arise under differential immune selection pressure. Through computational modeling coupled with experimental verification, we have been able to show that HIV sequences can be converted to quantitative fitness landscapes that predict viral vulnerabilities for rational immunogen design. In more recent studies we are using a new approach– structure-based network analysis– that applies network theory to protein structure data to quantitatively determine the importance of individual amino acids to the structure and function of HIV proteins, further defining regions of vulnerability that are being applied to immunogen design. Additional studies are examining the earliest immune responses induced following acute HIV infection, using a unique cohort of high risk uninfected women in KwaZulu Natal, South Africa who are followed twice weekly to identify cases of “hyperacute infection.”
Early treatment of these infections is providing important insights into the evolution of HIV-specific immune responses in the absence of CD4 T cell depletion.



Last Update: 6/18/2018



Publications

For a complete listing of publications click here.

 


 

1. Ferguson AL, Mann JK, Omarjee S, Ndung'u T, Walker BD, Chakraborty AK. Translating HIV Sequences into Quantitative Fitness Landscapes Predicts Viral Vulnerabilities for Rational Immunogen Design. Immunity. 2013 Mar 21; 38(3):606-17. PubMed PMID: 23521886.
2. Ndhlovu ZM, Kamya P, Mewalal N, Kløverpris HN, Nkosi T, Pretorius K, Laher F, Ogunshola F…… Chakraborty A, Dong K, Ndung'u T, Walker BD. Magnitude and Kinetics of CD8(+) T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point. Immunity. 2015 Sep 15; 43(3):591-604.
3. Ranasinghe, S., P. A. Lamothe, D. Z. Soghoian, S. W. Kazer, M. B. Cole, A. K. Shalek, N. Yosef, R. B. Jones, F. Donaghey, C. Nwonu, P. Jani, G. M. Clayton, F. Crawford, J. White, A. Montoya, K. Power, T. M. Allen, H. Streeck, D. E. Kaufmann, L. J. Picker, J. W. Kappler and B. D. Walker (2016). "Antiviral CD8+ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion." Immunity 45(4): 917-930.
4. Park RJ, Wang T, Koundakjian D, Hultquist JF, Lamothe-Molina P, Monel B, Schumann K, Yu H, Krupzcak KM, Garcia-Beltran W, Piechocka-Trocha A, Krogan NJ, Marson A, Sabatini DM, Lander ES, Hacohen N, Walker BD. A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors. Nat Genet. 2017;49(2):193-203
5. Clayton, K. L., D. R. Collins, J. Lengieza, M. Ghebremichael, F. Dotiwala, J. Lieberman and B. D. Walker (2018). "Resistance of HIV-infected macrophages to CD8(+) T lymphocyte-mediated killing drives activation of the immune system." Nat Immunol 19(5): 475-486.



© 2016 President and Fellows
of Harvard College