Shiv Pillai

Shiv Pillai, MD, PhD

Principal Investigator


Core Member

Ragon Institute of MGH, MIT and Harvard

Professor of Medicine and Health Sciences and Technology

Harvard Medical School

Director

Harvard Immunology PhD program

Contact


857.268.7005

Rm. 894

TikTok

B-cell biology and T-B collaboration

Research Overview

The Pillai lab has made fundamental discoveries about immune cells called B lymphocytes. This work has led to novel treatments currently in use in patients with B cell leukemias and autoimmune diseases. This laboratory also studies how immune cells can “go rogue” in autoimmune diseases like systemic sclerosis and IgG4-related disease, in patients with genetic disorders of the immune system, and in COVID-19 and other severe viral infections and uses the knowledge gained to collaborate with colleagues on clinical trials.

The Pillai lab explores the contributions of B cells to the development and function of T follicular helper cells and cytotoxic CD4+ T cells. We study these cells and their subsets in the context of inflammatory diseases like systemic sclerosis, IgG4-related disease, atherosclerosis, and COVID-19. We also explore how chromatin changes, including DNA methylation, influence B and T cell lymphocyte development, and B cell-T cell collaboration and immune function. We are interested in the development of subsets of T follicular helper cells and how alterations in T and B cell collaboration can drive different types of memory B cell responses, alter the durability of antibody responses, and may be of causal importance in severe infections like COVID-19.  We also investigate how novel single-gene mutations in humans alter regulatory T cell function and lead to a breakdown in B cell tolerance and thus cause autoimmunity.

Recognition and Media

Dr. Pillai received the Indian National Science Academy Medal for Young Scientists in 1980 and the Irving London Award for Excellence in Teaching, HST, from the Harvard Medical School in 2001. He received a Thomas McMahon mentoring award, from Harvard Medical School in 2013 and was named Harvard Crimson Professor of the Year in 2017. He directs an NIAID Autoimmune Center of Excellence at MGH. Dr. Pillai is a member of the American Association of Immunologists and the Federation of Clinical Immunology Societies.

About

Dr. Pillai received his medical degree at the Christian Medical College in Vellore, India, and a Ph.D. in Biochemistry from the University of Calcutta, working with Bimal Bachhawat. He was a postdoctoral fellow with David Baltimore at the Whitehead Institute and MIT and joined the faculty at MGH and the Harvard Medical School in 1988. Shiv is the author of “Lymphocyte Development” and the co-author with Abul Abbas and Andrew Lichtman of “Cellular and Molecular Immunology” and “Basic Immunology.” He heads the Harvard Immunology PhD and Masters' programs and directs courses in immunology at Harvard College, Harvard Medical School, the Federation of Clinical Immunology Societies, and the HMX platform.

Selected Publications

The ω Ig light chain: an 18 kd protein that forms disulfide-linked μ2ω2 tetramers in pre-B cells

Pillai S, Baltimore D.

Nature 1987; 329:172-174

Bruton’s tyrosine kinase is tyrosine phosphorylated and activated in pre-B lymphocytes and receptor ligated B cells

Aoki Y, Isselbacher KJ, Pillai S.

Proc. Natl. Acad. Sci. USA 1994; 91:10606-10609

Nuclear factor κ B is required for the development of marginal zone B lymphocytes

Cariappa A, Liou, HC, Horwitz B, Pillai S.

J.Exp. Med. 2000. 192, 1175-1182

The marginal zone versus follicular B lymphocyte cell-fate decision is regulated by Aiolos, Btk, and CD21

Cariappa A, Tang M, Parng C, Nebelitsky E, Carroll M, Georgopoulos K, Pillai S.

2001. Immunity 14, 603-615

Functionally defective germline variants of sialic acid acetylesterase in autoimmunity

Surolia I, Pirnie SP, Chellappa V, Taylor KN, Cariappa A, Moya J, Liu HY, Bell DW, Driscoll D, Diederichs S, Haider K, Netravali I, Le S, Elia R, Dow E, Lee A, Freudenberg J, DeJager PL, Chretien Y, Varki A, MacDonald ME, Gillis T, Behrens TW, Bloch D, Collier D, Korzenik J, Podolsky DK, Hafler D, Murali M, Sands B, Stone JH, Gregersen PK, and Pillai S.

Nature 2010, 466, 244-247

Decreased mTORC1 signaling and induction of metabolic quiescence define the transitional to follicular B cell switch

Farmer J, Allard-Chamard H, Sun N, Bertocchi A, Mahajan VS,Aicher T, Arnold J, Benson MD, Morningstar J, Barmettler S, Yuen J, Murphy SJH, Walter JR, Ghebremichael M, Shalek AK, Gerzsten R, Pillai S.

Science Signaling 2019 12(604). pii: eaaw5573. doi: 10.1126/scisignal.aaw5573

CD4+ cytotoxic T lymphocytes and apoptosis of HLA-DR expressing endothelial cells in systemic sclerosis

Maehara T*, Kaneko N*, Perugino CA*, Mattoo H, Kers J, Allard-Chamard H, Mahajan VS, Liu H, Murphy SJH, Ghebremichael M, Fox D, Payne AS, Lafyatis R, Stone JH, Khanna D, Pillai S.

J Clin Invest. 2020 130, 2451-2464

Loss of Bcl-6-expressing T follicular helper cells and germinal centers in COVID-19

Kaneko N, Kuo HH, Boucau J, Farmer JR, Allard-Chamard H,Mahajan VS, Piechocka-Trocha A, Lefteri K, Osborn M, Bals J, Bartsch YC, Bonheur N, Caradonna TM, Chevalier J, Chowdhury F, Diefenbach TJ, Einkauf K, Fallon J, Feldman J, Finn KK, Garcia-Broncano P, Hartana CA, Hauser BM, Jiang C, Kaplonek P, Karpell K, Koscher EC, Lian X, Liu H, Liu J, Ly NL, Michell AR, Rassadkina Y, Seiger K, Sessa L, Shin S, Singh N, Sun W, Sun X, Ticheli HJ, Waring MT, Zhu AL, Li JZ, Lingwood D, Schmidt AG, Lichterfeld M, Walker BD, Yu X, Padera RF, Pillai S and the Mass CPR specimen working group.

Cell, 2020. 183, 143-157. PMID: 32877699

Lab Team

Reetuparna Biswas

Graduate Student

Daniel DiToro

Postdoctoral Fellow

Jocelyn Farmer

Instructor In Medicine

Blythe Gulley

Project Coordinator

Kirsty Hillier

Postdoctoral Fellow

Naoki Kaneko

Postdoctoral Fellow

Marshall Karpel

Staff Scientist

Suparna Kumar

Graduate Student

Hang Liu

Postdoctoral Fellow

Vinay Mahajan

Instructor In Pathology

Zayd Mian

Undergraduate Student

Cory Perugino

Instructor In Medicine

Katie Premo

Research Technician I

Neal Shekar

Graduate Student

Tong Xu

Graduate Student

Grace Yuen

Postdoctoral Fellow

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