Pillai Lab

Research topics include: B cell Development and Lineage Commitment; A Novel Cell Surface Acetylation/Deacetylation Paradigm for Regulating Humoral Immunity and Development; Characterizing Peripheral Human B cells and B cells in Patients with Chronic Lymphocytic Leukemia


Shiv Pillai, MD, PhD
Professor of Medicine
Harvard Medical School

Associate Geneticist
Center for Cancer Research

Research Summary

The Pillai laboratory asks questions about the biology of the immune system and susceptibility to disease. Some of these questions are: 1) Can we manipulate the immune system to treat autoimmunity and cancer and to increase immunological memory? 2) Can we understand how genetics and the environment affect lymphoid clones to drive common diseases? and 3) Can this latter information be used to better understand and develop new therapies for chronic inflammatory human diseases such as systemic sclerosis and IgG4-related disease? Our discovery of the role of an enzyme called Btk in the activation of B cells has contributed to the generation of Btk inhibitors that are effective in B cell malignancies and in trials ofautoimmunity. One of the pathways we are currently studying suggests new approaches for the treatment of autoimmune disorders. We are also exploring novel ways to strengthen immune responses and enhance helper T cell memory that provides hope for developing more effective personalized immune-system based treatments for cancer.

Read the Pillai Lab's Annual Report in Full

Group Members

Shiv Pillai MD, PhD
Principal Investigator

Group Members

  • Hugues Allard-Chamard, MD, PhD
  • Faisal Alsufyani, MD
  • Alice Bertocchi
  • Edwin Delfin
  • Jocelyn Farmer, MD, PhD
  • Kelsey Finn*
  • Naoki Kaneko, DDS, PhD
  • Hang Liu, MD
  • Marshall Karpel*
  • Jesper Kers, MD, PhD
  • Vinay Mahajan, MD, PhD
  • Hamid Mattoo, PhD
  • Sam Murphey
  • Cory Perugino, DO
  • Na Sun
  • Grace Yuen, PhD

* PhD Candidate

Research Projects

Pathogenesis of fibrosis (NIAID Autoimmune Center of Excellence at MGH)

In studies on the immunology of IgG4 related disease and scleroderma, performed in collaboration with John Stone (MGH Rheumatology) and Dinesh Khanna, U. of Michigan, Rheumatology, we have identified an unusual, clonally expanded andpotentially fibrogenic human CD4+ effector T cell subset in affected tissues. The differentiation and protective role of these CD4+ CTLs in cancer and chronic viral infections is currently being investigated using chromatin accessibility mapping, DNA methylation studies and single cell RNA-seq approaches.

Studies on murine and human B cell development and activation

We are using a number of single cell transcriptomic, epigenetic and genetic approaches to examine the heterogeneity and development of murine and human B cells, as well as the molecular bases of the processes of T-B collaboration and germinal center formation.

DNA methylation, B cell self-renewal and chronic lymphocytic leukemia

We have long been interested in cell fate decisions in B cell development and in the development of self-renewing B cell subsets. The roles of DNMT3a in B-1a B cell self-renewal and of specific methylation events in chronic lymphocytic leukemia are being investigated.

Dock2 regulates T cell memory and T-B collaboration

We have identified Dock2 as a regulator of the strength of the immune response and the generation of CD8+ and CD4+ T cell memory. This gene also contributes the strength of the germinal center response. The inactivation of this gene leads to the clearance of intracellular pathogens and may enhance anti-tumor immunity.


View a list of publications by researchers at the Pillai Laboratory

Selected Publications

Maehara T, Mattoo H, Mahajan VS, Murphy SJH, Yuen GJ, Ishiguro N, Ohta M, Moriyama M, Saeki T, Yamamoto H, Yamauchi M, Daccache J, Kiyoshima T, Nakamura S, Stone JH and Pillai S. The expansion in lymphoid organs of IL-4+BATF+ T follicular helper cells is linked to IgG4 class switching in vivo. Life Science Alliance 2018 Epub April 13

Perugino C, Al Salem SB, Mattoo H, Della-Torre E, Mahajan VS, Ganesh G, Allard-Chamard H, Wallace Z, Montesi MB, Kreuzer J, Haas W, Stone JH, Pillai S. Identification of Galectin-3 as an auto-antigen in IgG4 related-disease. Journal of Allergy and Clinical Immunology 2018 Epub May 29

Fraschilla I, Pillai S. Viewing Siglecs through the lens of tumor immunology. Immunol Rev. 2017 Mar;276(1):178-191.

Yuen GJ, Demissie E, Pillai S. B lymphocytes and cancer: a love-hate relationship. Trends Cancer. 2016 Dec;2(12):747-757.


Contact Us

Pillai Laboratory

7th FloorBldg 149, 13th Street Charlestown, MA 02129

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