Walker Laboratory

Dr. Bruce Walker, Ragon Institute

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/ml without the need for antiviral medications have been recruited, and immunologic, virologic 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 a 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, a major effort is underway 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 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.

Laboratory Highlights

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 Recent Publications

1. Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES, Reddy S, Mackey EW, Miller JD, Leslie AJ, DePierres C, Mncube Z, Duraiswamy J, Zhu B, Eichbaum Q, Altfeld M, Wherry EJ, Coovadia HM, Goulder PJ, Klenerman P, Ahmed R, Freeman GJ, Walker BD. 2006. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443: 350-4

2. 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. 2007. Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction. Nat Immunol 8: 1246-54

3. Chen H, Piechocka-Trocha A, Miura T, Brockman MA, Julg BD, Baker BM, Rothchild AC, Block BL, Schneidewind A, Koibuchi T, Pereyra F, Allen TM, Walker BD. 2009. Differential neutralization of human immunodeficiency virus (HIV) replication in autologous CD4 T cells by HIV-specific cytotoxic T lymphocytes. J Virol 83: 3138-49

4. Miura T, Brockman MA, Brumme ZL, Brumme CJ, Pereyra F, Trocha A, Block BL, Schneidewind A, Allen TM, Heckerman D, Walker BD. 2009. 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 83: 140-9

5. Kosmrlj A, Read EL, Qi Y, Allen TM, Altfeld M, Deeks SG, Pereyra F, Carrington M, Walker BD, Chakraborty AK. 2010. Effects of thymic selection of the T-cell repertoire on HLA class[thinsp]I-associated control of HIV infection. Nature 465: 350-4

6. The International HIV Controller Study. 2010. The major genetic determinants of HIV control affect HLA class I peptide binding. Science in press

Principal Investigator: Bruce D. Walker, MD

Office/Location: 400TS 870
Assistant:Gaby Berger
Phone: (857) 268-7073

Laboratory Staff

Alicja Piechocka-Trocha
Senior Laboratory Manager
Alicja is a Senior Laboratory Manager for the Ragon Institute and has been working for Dr. Bruce Walker for the last 24 years. Trained as a veterinarian from Polish Agriculture University in Olsztyn, she began to perform research, and despite all odds, she truly learned to love it. The aspect of teaching and educating future aspiring scientist as well as cultivating all habits of safe and meticulous lab work in young students and fellows has become a professional journey for her. What they learn with Alicja they will apply in their new endeavors. When not at work she enjoys reading books, long nature walks and skiing.
Kiera Clayton
Postdoctoral Fellow
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.
Paolo Di Pinto
Research Technician
Paolo joined the Walker laboratory in August 2016 as a research technician under the direction of Adrienne Yanez. He attended Northeastern University, majoring in Biology with a minor in Italian. He first became interested in research when he obtained my first internship at Brigham and Womens Hospital in Dr. Raina Fichorova’s laboratory, studying experimental and clinical vaginal lavage samples looking to identify inflammation biomarkers for ovarian cancer. Paolo is originally from Florida and enjoys swimming, tennis, and longs walk on the beach. He plans to pursue a master’s degree in biotechnology and continue doing disease research, focusing on oncology.
Gaurav Gaiha
Originally from Chicago, Gaurav completed his BS in Biochemistry and BA in Economics from the University of Illinois. He obtained a PhD in Biochemistry with a focus in HIV immunology at Oxford University working in the MRC Immunochemistry Unit in collaboration with the MRC Human Immunology Unit. After Oxford, Guarav moved onto the Health Sciences and Technology (HST) program at Harvard Medical School to complete his MD, which he completed with Magna Cum Laude honors. Gaurav is now an Internal Medicine Resident at Massachusetts General Hospital, actively pursuing projects in the lab. His research interests are focused on understanding the properties that define successful and dysfunctional HIV-specific CD8+ T cell responses in patients with divergent clinical outcomes using transcriptional profiling and shRNA knockdown technology. He is also working on a novel network analysis platform to identify critical areas of mutational constraint within the HIV proteome and ultimately hope to parlay this work into novel T-cell based vaccine designs.
Itai Muzhingi
Research Technician
Itai Muzhingi is a rising junior at Amherst College, majoring in Biochemistry and Biophysics. A science enthusiast, he is highly interested in infectious disease research and hopes to pursue an MD/PhD in the near future. He is passionate about discovering affordable, accessible and easily administered methods of boosting the immune system in response to HIV infection. Under the mentorship of Dr. Gaurav Gaiha, Itai is currently performing a genome-wide CRISPR Screen of the pathways and molecules involved in the HLA Class I expression of an HIV epitope on Dendritic Cells. Before joining the Walker lab, Itai worked on developing a method of quantifying molecular Near Attack Conformations using computational chemistry techniques. In the long run, he hopes to use the research skills that he acquires to promote research and STEM education in his home country, Zimbabwe. Outside of work, Itai enjoys listening to music, hiking and exploring his artistic side with the aid of 3D modeling and animation platforms.
Ryan Park
Post Doctoral Fellow
Ryan is an MD student at Harvard Medical School. He received a B.S. and an M.S. in Molecular Biophysics and Biochemistry from Yale University in 2012. He is in the Harvard-MIT Health Sciences & Technology (HST) program and joined the Walker lab in January 2013 for his thesis project. He’s originally from Los Angeles but has also lived in Chicago, Fort Worth, and Seoul. In the lab, he is trying to understand the mechanism for the differential function of CD8+ T cell clones from Elite Controllers and Chronic Progressors. In his dwindling time outside of the lab and classroom, he enjoys cooking, playing the saxophone, and reading and dreaming about fast cars.
Chioma Anthonia Nwonu
Research Technician
Chioma joined the Walker laboratory in September 2015 as a research technician under the direction of Srinika Ranasinghe. She attended Smith College where she majored in Biochemistry with a strong background in molecular biology. She previously worked in a laboratory at Smith College that studies the molecular biology of lymphatic filariasis, a neglected tropical disease. She hopes to pursue a career in medicine and clinical research. Chioma is from Nigeria and enjoys cooking traditional Nigerian dishes.
Joshua Lengieza
Research Technician
Josh joined the Walker Lab in May 2016 as a research technician working under Kiera Clayton. He graduated from MCPHS University with a B.S. in Medical and Molecular Biology. During his undergraduate studies, he worked on nociceptors and their involvement in immune responses. Currently, he is looking at mechanisms responsible for T cell detachment from killed targets as well as characterizing cytolytic HIV-specific CD8+ T cells. Outside of the lab Josh enjoys hiking, going to the beach and reading.
Adrienne Yanez
Research Fellow
Adrienne joined the Walker lab as a research fellow in March 2015. She is working to identify and manipulate gene regulatory networks that improve HIV-specific CD4 T-cell responses to HIV infection. She received her Ph.D. from Harvard University, where she studied global regulation of miRNA activity by translation initiation factors in melanoma. In her spare time, she enjoys playing outside, exploring her surroundings, and gazing into empty centrifuges (see picture above).
Priya Jani

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