Bruce Walker, MD

Lab Info:

Principal Investigator: Bruce Walker, MD

Office/Location: 400TS 870

Phone: (857) 268-7073

Email: bwalker@partners.org | Assistant: Marissa Ferrara, mdferrara@mgh.harvard.edu

Category: Core Members, Ragon Members, Steering Committee

Dr. Bruce D. Walker is the founding Director of the Ragon Institute of MGH, MIT and Harvard.


Dr. Walker is a world leader in the study of immune control and evasion in HIV infection. He was the first to describe HIV-specific CD8+ T cells (with Robert Schooley and Martin Hirsch) (Walker et al., Nature, 1987) and HIV-specific CD4+ T-cell responses (Rosenberg et al., Science, 1997), and he has defined the role and fate of these cells in acute and chronic HIV infection and transmission (e.g., Walker et al., Science, 1988; Rosenberg et al., Nature, 2000; Goulder et al., Nature, 2001; Altfeld et al., Nature, 2002; Ndhlovu et al, Immunity 2015). He also discovered the role of immune checkpoints in dysfunctional cellular immune responses to HIV (Day et al., Nature, 2006; Kaufmann et al., Nat Immunol, 2007) and has characterized both host and viral genetic factors involved in modulating viral control (Pereyra et al., Science, 2010; Ferguson et al., Immunity, 2013; Park et al., Nat Genet, 2017).


In 1998, Dr. Walker began scientific collaboration with African scientists in KwaZulu-Natal Province, South Africa. Through the work of Dr. Walker and others, this collaboration eventually led to the establishment of the Doris Duke Medical Research Institute (DDMRI) at the Nelson Mandela School of Medicine in 2003, the first ever dedicated medical research institute at an African university. In 2012, the DDMRI expanded into the KwaZulu-Natal Research Institute for TB and HIV (K-RITH), for which Dr. Walker was a founding co-director. This institute, recently renamed the Africa Health Research Institute, was funded initially by the Howard Hughes Medical Institute and more recently by the Wellcome Trust.


Along with Ragon Institute colleagues Thumbi Ndung’u, Krista L. Dong, and Douglas S. Kwon, Dr. Walker was integral in establishing the FRESH (Females Rising through Education, Support and Health) study in KwaZulu-Natal, South Africa. This effort has successfully merged characterization of the immunology and virology of acute HIV infection with social good in the heart of the African HIV epidemic (Ndung’u et al., Sci Immunol, 2017). Dr. Walker was also instrumental in establishing the MIT course ‘Evolution of an Epidemic’, through which MIT undergraduates across disciplines examine the medical, scientific, policy, and public health responses to the AIDS epidemic through an immersive experience in Durban, South Africa.


Dr. Walker is a Professor of Medicine at Harvard Medical School, Professor of the Practice of Medicine at MIT, and Professor of Medicine at the Nelson Mandela School of Medicine at the University of KwaZulu-Natal in Durban, South Africa. He is also a Howard Hughes Medical Institute investigator.


Dr. Walker is an elected member of the National Academy of Medicine and the American Academy of Arts and Sciences, as well as an elected fellow of the American Academy of Microbiology and the American Association for the Advancement of Science. He is the recipient of numerous awards, including the NIH Merit Award and the Doris Duke Distinguished Clinical Scientist Award.


Dr. Walker received a BS in chemistry from the University of Colorado, Boulder, and an MD from Case Western Reserve University. He completed his internship and residency in internal medicine at MGH and Harvard Medical School, followed by an internship in pathology and fellowship training in infectious disease at MGH and Harvard Medical School.  He is board-certified in both internal medicine and infectious disease.


Listen to Dr. Walker interview actress and activist Elizabeth Taylor about her work on HIV!


Important Accomplishments

  • Identification of strong circulating HIV-specific cytotoxic T lymphocytes in infected persons.
  • Identification of HIV-specific CD4 T cells and their association with immune control of HIV.
  • Identification of immunoregulatory pathways that turn HIV-specific immune responses off in vivo.
  • Demonstration of the superior antiviral efficacy of Gag-specific CD8 T cell responses.

Present Areas of Investigation

  • Define the relative antiviral efficacy of epitope-specific CTL responses in infected persons
  • Define the predicatable pathways to immune escape in infected persons
  • Define the mechanisms that underlie effective cell killing
  • Define the mechanisms of spontaneous control of HIV infection using a genome wide association scan.

Selected Publications

1.   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 individuals. Nature. 1987; 328(6128):345-348.

Link to PubMed

2.   Walker BD, Flexner C, Paradis TJ, Fuller T, Hirsch MS, Schooley RT, Moss B.  HIV-1 reverse transcriptase is a target for cytotoxic T lymphocytes in infected individuals.  Science 1988; 240:64-66.

Link to PubMed

3.   Yang OO, Kalams SA, Trocha A, Cao H, Luster A, Johnson RP, Walker BD.  Suppression of human immunodeficiency virus type 1 replication by CD8+ cells: Evidence for HLA class I-restricted triggering of cytolytic and noncytolytic mechanisms.  J Virol 1997; 71:3120-3128.

Link to PubMed

4.   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):334-338.

Link to PubMed

5.   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.

Link to PubMed

6.   Kaufmann DE, Lichterfeld M, Altfeld M, Addo MM, Johnston MN, Lee PK, Wagner BS, Kalife ET, Strick D, Rosenberg ES, Walker BD. Limited Durability of Viral Control following Treated Acute HIV Infection. PLoS Med. 2004 Nov;1(2):e36. Epub 2004 Oct 26.

Link to PubMed

7.   Altfeld M, Allen TM, Yu XG, Johnston MN, Agrawal D, Korber BT, Montefiori DC, O’Connor DH, Davis BT, Lee PK, Maier EL, Harlow J, Goulder PJR, Brander C, Rosenberg ES, Walker BD. HIV superinfection despite broad CD8+ T-cell responses containing replication of the primary virus. Nature.  2002 Nov 28; 420:434-439.

Link to PubMed

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):350-354.

Link to PubMed

9.   Kaufmann DE, Kavanagh DG, Pereyra F, Zaunders JJ, Mackey EW, Miura T, Palmer S, Brockman M, Rathod A, Piechocka-Trocha A, Baker B, Zhu B, Le Gall S, Waring MT, Ahern R, Moss K, Kelleher AD, Coffin JM, Freeman GJ, Rosenberg ES, Walker BD. Upregulation of CTLA-4 by HIV-specific CD4 (+) T cells correlates with disease progression and defines a reversible immune dysfunction. Nat Immunol. 2007 Nov; 8(11):1246-1254.

Link to PubMed

10.   Gaiha G, McKim KJ, Woods M,  Pertel T, Rohrbach J, Barteneva N, Chin CR, Liu D, Soghoian DZ, Cesa K, Wilton S, Waring MT, Chicoine A, Doering T, Wherry J, Kaufmann, D, Lichterfeld M, Brass AL  & Walker BD.  Dysfunctional HIV-specific CD8+ T cell proliferation is associated with increased caspase-8 activity and mediated by necroptosis.  Immunity 41(6): 1001-1012.

Link to PubMed

11.   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.

Link to PubMed

12.   Pereyra F, Jia X, McLaren PJ, Telenti A, De Bakker P, Walker BD et al. 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.

Link to PubMed

13.   Miura T, Brockman MA, Brumme ZL, Brumme CJ, Pereyra F, Trocha A, Block BL, Schneidewind A, Allen TM, Heckerman D, Walker BD. HLA-associated alterations in replication capacity of chimeric NL4-3 viruses carrying gag-protease from elite controllers of human immunodeficiency virus type 1. J Virol. 2009 Jan; 83(1):140-149.

Link to PubMed

14.   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):606-617.

Link to PubMed

15.   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.

Link to PubMed

16.   Kiepiela P, Leslie AJ, Honeyborne I, Ramduth D, Thobakgale C, Chetty S, Rathnavalu P, … Bunce M, Barber LD, Szinger J, Day C, Klenerman P, Mullins J, Korber B, Coovadia HM, Walker BD, Goulder PJ. Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature. 2004;432(7018):769-775.

Link to PubMed

17.   Kiepiela P, Ngumbela K, Thobakgale C, Ramduth D, Honeyborne I, Moodley E, Reddy S, … 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.

Link to PubMed

18.   Radebe M, Gounder K, Mokgoro M, Ndhlovu ZM, Mncube Z, Mkhize L, van der Stok M, Jaggernath M, Walker BD, Ndung’u T. Broad and persistent Gag-specific CD8+ T-cell responses are associated with viral control but rarely drive viral escape during primary HIV-1 infection. AIDS. 2015;29(1):23-33.

Link to PubMed

19.   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.

Link to PubMed

20.   Gaiha GD, Rossin EJ, Urbach J, Landeros C, Collins DR, Nwonu C, Muzhingi I, Anahtar MN, Waring OM, Piechocka-Trocha A, Waring M, Worrall DP, Ghebremichael MS, Newman RM, Power KA, Allen TM, Chodosh J, Walker BD. Structural topology defines protective CD8(+) T cell epitopes in the HIV proteome. Science. 2019 May 3;364(6436):480-484.

Link to Full Text

21.   Ndhlovu ZM, Kazer SW, Nkosi T, Ogunshola F, Muema DM, Anmole G, Swann SA, Moodley A, Dong K, Reddy T, Brockman MA, Shalek AK, Ndung’u T, Walker BD. Augmentation of HIV-specific T cell function by immediate treatment of hyperacute HIV-1 infection. Science Translational Medicine. 2019 May 22; 11(493):eaau0528.

Link to Full Text

Relevant Links

Laboratory Staff

Name: Kiera Clayton

Email: klclayton@partners.org

Bio: Kiera Clayton is a Postdoctoral Fellow who joined the Walker Lab in December of 2014. Her work focuses on understanding how co-inhibitory pathways play a role in modulating HIV-specific responses and their impact on protective T cell memory formation during HIV infection. She obtained an Honors BS in Biochemistry followed by her PhD in Immunology, both from the University of Toronto in Canada. During her PhD, she studied the co-inhibitory molecule, Tim-3, and characterized its function and regulation in human CD8+ T cells. In her free time, she enjoys running, skiing, wine tasting, and jazz.


Name: David Collins

Email: drcollins@mgh.harvard.edu

Education: Ph.D., University of Michigan; B.S., University of Rochester

Hometown: Defreestville, New York

Bio: David joined the Walker lab as a Research Fellow in 2015. His research aims to elucidate molecular regulation of antiviral CD8+ T cell dysfunction in HIV-infected individuals. Outside of lab, David enjoys a quiet life with his feline overlords.


Name: Xiaolong Li

Email: xiaolong@crystal.harvard.edu

Education: Ph.D., University of Science and Technology of China, Peking University, and Dana Farber Cancer Institute

Hometown: Anhui province of China, the hometown of Yellow Mountain

Bio: Xiaolong is a research fellow at the Dana-Farber Cancer Institute and the Ragon Institute. He is originally from China and received his Ph.D. in biochemistry and structural biology from the University of Science and Technology of China (USTC) in 2016. He began his graduate education at USTC (2011) then completed his Ph.D program at Peking University (2012-2014) and Dana-Farber Cancer Institute (2014-2016). He has a background in crystallography, biochemistry and molecular biology. He has experiences in biochemical and structural studies of receptor protein, kinase, antibody and axon guidance cue.  However, he has been focusing on structural studies of peptide-HLA (pHLA), TCR and pHLA/TCR complex for a long time. By determining protein structures, he is gaining insight into the molecular mechanism involved in HIV-1 elite controllers who have enhanced CTL responses and cross reactivity for the control of antigen mutations. In his free time, he enjoys hiking, biking and skiing.


Name: Itai Muzhingi

Email: imuzhingi@mgh.harvard.edu

Education: B.A. in Biochemistry and Biophysics, Amherst College

Hometown: Chitungwiza, Zimbabwe

Bio: Itai Muzhingi is a Research Technician in the Walker Lab working under Dr. Gaurav Gaiha. He is testing the efficacy of various HIV vaccines, studying the immunological effects of SNPs in HLA-B57 and screening for host factors that mediate Nef-induced HLA class I downregulation. In college, Itai elucidated a regulatory mechanism for acetyl-CoA synthetase expression in Vibrio cholerae. He is passionate about promoting African talent in the STEM fields. Itai enjoys listening to music and exploring anything that he considers to be truly novel.


Name: Geetha Mylvaganam   

Email: gmylvaganam@partners.org

Education: Ph.D., Emory University

Hometown: Longmeadow, MA but was born in Miami, FL

Bio: Geetha Mylvaganam was born in Miami, FL but grew up in Western Massachusetts. She is a Research Fellow who joined the Walker Lab in July of 2016. Her work focuses on understanding mechanisms regulating CD8 T cell function and localization within lymphoid tissue during HIV infection. A better understanding of these mechanisms will lead to the development of novel HIV therapeutics that can enhance trafficking of CD8 T cells to sites of HIV persistence. She obtained her PhD from Emory University in the Immunology and Molecular Pathogenesis program in 2016, where she identified novel T cell subsets within lymphoid tissue during pathogenic SIV infection and assessed the therapeutic effects of PD-1 blockade on anti-viral immunity and destabilization of the viral reservoir during suppressive anti-retroviral therapy. In her free time, Geetha enjoys working out, watching reality TV, socializing with friends, and long-walks.


Name: Zachary Racenet

Email: zracenet@mgh.harvard.edu

Education: B.S. in Biology, Castleton State University

Hometown: Danville, Vermont

Bio: Zachary returned to academia after spending a few years being a technician in industry in hopes of pursing a Ph.D. Originally from northern Vermont, he attended Castleton University and focused his studies on cellular metabolism. Despite beginning his studies outside the realm of immunology he is captivated by the responsiveness and complexity of the immune system as well as the subversive nature of viruses. He works with David Collins researching T-cell dysfunction. Zachary spends his free time pursuing fitness and learning about technology and electronics.


Name: Peter Shahinian

Email: pshahinian@mgh.harvard.edu

Education: B.S., B.A., Boston University; M3, Texas Tech University Health Sciences Center

Hometown: El Paso, Texas

Bio: Peter is a medical student from Texas Tech University who is doing a research year in the Walker Lab before returning to complete his fourth year of medical education. After graduation, he is planning on pursuing a residency in internal medicine. His current research interests are in understanding T-cell cross reactivity, engineering CAR-T cells, and manipulating the immune system in order to treat chronic disease. In his free time, he likes to tend to his indoor garden and digs through SoundCloud for the next up and coming hip-hop artist. He also thinks he’s good at playing the ukulele.


Name: Nishant Kumar Singh

Email: nsingh0@mgh.harvard.edu

Education: Ph.D., University of Notre Dame

Hometown: Jamshedpur, India

Bio: Nishant Singh is a joint Research Fellow in the Walker Lab and the Birnbaum Lab at Koch Institute at MIT. He received his Ph.D. in Biochemistry at the University of Notre Dame in 2019. At Notre Dame, he worked for Dr. Brian Baker, where he conducted structural and biophysical characterization of T cell receptor (TCR) variants with the goal to better understand the factors that govern antigen specificity and TCR mediated signaling in T cells. Since joining the Walker Lab, he has been working on defining the role of TCR recognition and signaling in immune control of HIV infection, using a unique, well-pedigreed bank of human samples. In general, he is interested in understanding the transcriptional and immunologic profiles of T cell responses in HIV infected individuals and recipients of candidate vaccines. In his free time, he likes to read books, run by the river and spend time with friends.


Name: Heather Stuart

Email: hastuart@mgh.harvard.edu

Education: Honors B.S. in Pharmaceutical Sciences, University of Rhode Island

Hometown: Warren, Rhode Island

Bio: Heather is a Research Technician in the Walker Lab working under Kiera Clayton. Her undergraduate studies focused on pharmaceutical science. She previously worked as a research associate intern in a pharmaceutical compounding lab. Her research interests shifted from pharmaceuticals to immunology after completing her senior honors project on EBV’s role in cancer. She plans to pursue a Ph.D. in immunology. In her free time, she enjoys taking care of her pet mice and her aquariums.


Name: Alicja Trocha

Email: atrocha@partners.org

Education: DVM, Polish Agriculture University

Hometown: Gdansk, Poland

Bio: Alicja Trocha is a Senior Laboratory Manager who has worked for Dr. Bruce Walker for many years. She started that journey when the Walker Lab had only handful of members and was embarking on the great expedition to become one of the most recognized leaders in HIV and Immunology research. Trained as veterinarian in Poland, she thought that this job would be the starting point of becoming one in America. Instead, it turned out to be a dream come true. Working alongside a world-class visionary and true leader, the job became incredibly fulfilling in its mission to make an everlasting imprint on the future. Starting as lab technician, she became an expert of growing, cultivating and establishing CD8 T-cells, and now the Walker Lab can call itself the world’s largest repository of HIV CD8 T cells. Over the many years, she has participated in numerous exciting and exceptional projects and was a part of the personal journeys of many Postdocs, Research Fellows and Technicians. In recent years, the move to the 400 Technology Square building brought a considerable expansion in space and research potential with the addition of many new members, and her role has grown to help manage that progress and minimize the obstacles. In her free time, Alicja enjoys nature walks, biking, a good book, and new adventures.


Name: Onyinyechi Ukaire (Ukay)

Email: oukaire@mgh.harvard.edu

Education: B.S. in Biochemistry and Computer Science, Tufts University

Hometown: Abuja, Nigeria

Bio: After graduating in May 2018, Ukay joined Bruce Walker’s lab as a research technician in bioinformatics under the mentorships of Adrienne Yanez and Jonathan Urbach. By applying computational techniques, Ukay organizes, analyzes and visualizes gene expression data from RNA sequencing of HIV-specific CD4+ and CD8+ T cells. He has developed his own informatics pipelines, which he will deploy again for future projects. In his free time, he enjoys stepping out of his comfort zone to do something new. Recently, he cooked butter chicken and ramen; surprisingly, they both turned out well and their pictures ended up on Instagram. Importantly, he loves A Song of Ice and Fire by George R.R. Martin and wrote predictions on events that would unfold. For current news, please see oukaire.com.


Name: Jonathan Urbach

Email: jurbach@mgh.harvard.edu

Education: A.B., Cornell University; Ph.D., Harvard University

Hometown: Annapolis, Maryland

Bio: Jonathan is a bioinformatics specialist, who joined the Walker lab in May 2017. Jonathan completed his Ph.D. in Chemistry in the laboratory of Jack Szostak, then worked 15 years as a bioinformatician in the lab of Fred Ausubel studying innate immunity. His main research focus is on the transcriptional changes that occur in CTLs of elite and viremic HIV controllers leading up to the loss of control. He’s also interested in how structural information can be used to predict amino acid mutational tolerance in proteins and predict optimal epitopes for vaccines to elicit cellular immune responses. In his spare time, he runs the Ragon Bioinformatics Working Group and listens to loud music.


Name: Alonso Villasmil Ocando

Email: avillasmilocando@mgh.harvard.edu

Education: B.A. in Biology, Williams College

Hometown: Orlando, Florida

Bio: Alonso is a Research Technician in the Walker Lab. As an HHMI EXROP fellow in the Walker Lab during the summer of 2017, he worked on understanding the transcriptional regulation of T cell trafficking and lymph node dynamics. After graduating from Williams College with a B.A. in Biology, he rejoined the lab and is currently investigating CAR T cell therapies against HIV. Outside of lab, Alonso enjoys walks along the Esplanade, dancing, and planning his next travel adventures.


Name: Olivia Mae Waring

Email: omwaring@mit.edu

Education: B.A. Princeton University; M.St. Oxford University; S.M. Harvard-MIT HST Division

Hometown: Morristown, New Jersey

Bio: Olivia is a graduate student researcher in the Medical Engineering and Medical Physics program at Harvard and MIT. She is expanding upon the Walker Lab’s signature structure-based network analysis approach to vaccine design under the supervision of Gaurav Gaiha and Lizzy Rossin. A former software engineer, journalist, linguist, and aspiring Doctors Without Borders physician, Olivia’s long-term research interests include humanitarian aid, disaster relief, and global public health in resource-limited contexts. When not coding, Olivia enjoys singing, acting, playing violin, learning languages, watching Bollywood films, and rearing guinea pigs.


Name: Adrienne Yanez

Email: adrienneg_yanez@dfci.harvard.edu      

Education: B.S. University of Notre Dame; Ph.D. Harvard University

Hometown: Lake Station, Indiana

Bio: Adrienne is a Research Fellow in the Walker Lab. Her thesis work focused on the mechanism of miRNA-mediated translational repression and the global regulation of miRNA activity by translation initiation factors in melanoma. She is working to identify and manipulate gene regulatory networks that control HIV-specific CD4+ T cell functions in HIV infection. In her spare time, she enjoys playing outside and performing as a background extra in exclusive Ragon film productions.


Former Laboratory Members