Ragon Institute
400 Technology Square
Cambridge, MA 02139
Degrees
- MD, Case Western Reserve University
- BA in Chemistry, University of Colorado
Bio
Dr. Bruce Walker is the founding Director of the Ragon Institute of MGH, MIT, and Harvard, a Professor of Medicine at Harvard Medical School, Professor of Practice at MIT, and a Howard Hughes Medical Institute (HHMI) Investigator. In addition to his clinical duties as a board certified Infectious Disease specialist, his research focuses on cellular immune responses in chronic human viral infections, with a particular focus on HIV immunology and vaccine development. He leads an international translational clinical and basic science research effort to understand how some rare people who are infected with HIV, but have never been treated, can fight the virus with their immune system. Dr. Walker is also an Adjunct Professor at the Nelson Mandela School of Medicine in Durban, South Africa. There he collaborates with the Doris Duke Medical Research Institute at the University of KwaZulu-Natal and serves as a Principal Investigator in the HIV Pathogenesis Program, an initiative to study the evolution of the HIV and the immune responses effective in controlling this virus, as well as to contribute to training African scientists. He is a co-founder of the the KwaZulu-Natal Research Institute for TB and HIV (K-RITH, recently renamed the Africa Health Research Institute), an initiative initially funded by HHMI to build a state of the art TB-HIV research facility at the heart of these dual epidemics in South Africa. Dr. Walker is also a member of the American Academy of Arts and Sciences, American Society for Clinical Investigation (ASCI), the American Association of Physicians (AAP), and the Institute of Medicine (IOM) of the National Academy of Sciences.
Research Interests
The Walker laboratory focuses on mechanisms of immune control in HIV infection, focusing in particular on persons who control HIV infection spontaneously without the need for medication. Through an international collaboration now funded by the Gates Foundation, more than 1500 persons who control HIV infection to less than 2000 RNA Copies/mil without the need for antiviral medications have been recruited, and immunologic, virology and host genetic mechanisms accounting for this remarkable phenotype are being investigated. Our results, published in Science, indicate that the major genetic determinants of HIV control affect the nature of the peptide-HLA binding. We are currently focusing our research efforts on this interaction and how it impacts the inductive and effector phases of the CD8 T cell response.
Other projects currently underway are building on an observation that the antiviral efficacy of CTL varies dramatically among different epitopes and different restricting HLA alleles, in an attempt to define the major antiviral effector functions and apply these to vaccine development. At the same time, efforts are underway to define the subset of CD8 T cell responses that exert the strongest antiviral effect, and to define those responses that are simply passengers and fail to contribute to immune control.
In addition to these efforts in Boston, we are undertaking a major project at our laboratory at the Nelson Mandela School of Medicine at the University of KwaZulu-Natal, South Africa, where a major population based effort is underway to define evolution of clade C virus infection under immune selection pressure, and to define the predictable pathways to immune escape. We have established a mechanism for recruitment of persons with acute HIV infection by screening persons who test antibody negative at VCT (now HCT) sites in KZN. We anticipate an expanding collaboration with persons at the Ithembalebantu Clinic in Umlazi to accelerate these studies, which will include examination of tissue biopsies.
Selected Awards/Societies
- Bernard Fields Lectureship, 2015
- NIH Merit Award, 2011, 2004
- American Academy of Arts and Sciences, 2010
- National Academy of Medicine, 2009
- American Association of Physicians, 2000
- Doris Duke Charitable Foundation Distinguished Clinical Scientist Award, 1999
- American Society for Clinical Investigation, 1993
- Alpha Omega Alpha Medical Honor Society, 1980
- Phi Beta Kappa, 1975
Selected Publications
- Walker BD, Chakrabarti S, Moss B, Paradis TJ, Flynn T, Durno AG, Blumberg RS, Kaplan JC, Hirsch MS, Schooley RT. HIV-specific cytotoxic T lymphocytes in seropositive inidividuals. Nature. 1987; 328(6128):345-8.
- Rosenberg ES, Billingsley JM, Caliendo AM, Boswell SL, Sax P, Kalams SA, Walker BD. Vigorous HIV-1-specific CD4+ T cell responses correlate with control of viremia. Science 1997; 278:1447-1450.
- Rosenberg ES, Altfeld M, Poon SH, Phillips MN, Wilkes BM, Eldridge RL, Robbins GK, D’Aquila RT, Goulder PJ, Walker BD. Immune control of HIV-1 after early treatment of acute infection. Nature 2000; 407(6803):523-6.
- Goulder PJ, Brander, C, Tang Y, Tremblay C, Colbert RA, Addo MA, Rosenberg ES, Nguyen T, Allen R, Trocha A, Altfeld M, He S, Bunce M, Funkhouser R, Pelton SI, Burchett SK, McIntosh K, Korber BTM, Walker BD. Evolution and transmission of stable CTL escape mutations in HIV infection. Nature. 2001; 412(6844):334-8.
- Day C.L., Kaufmann D.E., Kiepiela P., Brown JA., Moodley ES., Reddy S., Mackey EW., Miller J.D., Leslie A.J., DePierres C., Mncube Z., Duraiswamy J., Zhu B., Eichbaum Q., Altfeld M., Wherry E.J., Coovadia H.M., Goulder P.J., Klenerman P., Ahmed R., Freeman GJ., Walker B.D. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature. 2006 Sep 21; 443(7109):350-4.
- Kiepiela P, Ngumbela K, Thobakgale C, Ramduth D, Honeyborne I, Moodley E, Reddy S, de Pierres C, Mncube Z, Mkhwanazi N, Bishop K, van der Stok M, Nair K, Khan N, Crawford H, Payne R, Leslie A, Prado J, Prendergast A, Frater J, McCarthy N, Brander C, Learn GH, Nickle D, Rousseau C, Coovadia H, Mullins JI, Heckerman D, Walker BD, Goulder P. CD8(+) T-cell responses to different HIV proteins have discordant associations with viral load. Nat Med. 2007 Jan;13(1):46-53.
- Pereyra F, Jia X, McLaren PJ, Telenti A, De Bakker P, Walker BD. The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation; The International HIV Controller Study. Science 2010 Dec 10; 330(6010):1551-1557. [Epub ahead of print] 2010 Nov 4 PubMed PMID: 21051598
- Chen H, Ndhlovu ZM, Liu D, Porter LC, Fang JW, Darko S, Brockman MA, Miura T, Brumme ZL, Schneidewind A, Piechocka-Trocha A, Cesa KT, Sela J, Cung TD, Toth I, Pereyra F, Yu XG, Douek DC, Kaufmann DE, Allen TM, Walker BD. TCR clonotypes modulate the protective effect of HLA class I molecules in HIV-1 infection. Nat Immunol. 2012 Jun 10; 13(7):691-700. doi: 10.1038/ni.2342. PubMed PMID: 22683743
- Ndhlovu ZM, Kamya P, Mewalal N, Kløverpris HN, Nkosi T, Pretorius K, Laher F, Ogunshola F, Chopera D, Shekhar K, Ghebremichael M, Ismail N, Moodley A, Malik A, Leslie A, Goulder PJ, Buus S, 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. doi: 10.1016/j.immuni.2015.08.012. Epub 2015 Sep 8. PubMed PMID: 26362266; PubMed Central PMCID: PMC4575777.
Courses Taught
- AIDS: Evolution of an Epidemic