Pillai

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

Overview

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 human genetics. Some of these questions are: 1) Can we manipulate the immune system to treat 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 arthritis, lupus 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 of autoimmunity. One of the pathways we are currently studying suggests new approaches for the treatment of autoimmune disorders. We have also found a novel way 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

  • Faisal Alsufyani, MD
  • Joe Daccache
  • Ezana Demissie*
  • Jefte Drijvers, MD
  • Isabella Fraschilla
  • Takashi Maehara, DDS, PhD
  • Vinay Mahajan, MD, PhD
  • Hamid Mattoo, PhD
  • Cory Perugino, DO
  • Ian Rosenberg, PhD
  • Vinay Vishwanadham
  • Kai Xin, PhD
  • Kelley Xing

* PhD Candidate

Research Projects

A novel human T cell subset that drives 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 in Rheumatology, we have identified an unusual, clonally expanded and potentially “fibrogenic” human CD4+ effector T cell subset. The differentiation and protective role of these CD4+ CTLs in cancer and chronic viral infections is currently being investigated.

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.

Studies on the genesis of plasmacytoid dendritic cells

The origins of plasmacytoid dendritic cells have long been controversial. We have identified unique bone marrow progenitors that exclusively give rise to plasmacytoid dendritic cells without differentiating into conventional dendritic cells. This work is generating new insights as to the nature of the myeloid versus lymphoid split during hematopoietic cell development.

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.

A novel murine gene on chromosome 11 that regulates T cell memory and T-B collaboration

We have defined a novel locus on murine chromosome 11 that regulates 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.  The identification and characterization of this gene using genetic approaches is currently in progress.

9-O-acetylation of sialic acid and the regulation of autoimmunity

We are currently examining the link between enhanced 9-O-acetylation of sialic acid and a linked propensity towards autoimmunity in mice and humans.

Publications

View a list of publications by researchers at the Pillai Laboratory

Selected Publications

Mahajan VS, Pillai S, Sialic Acids and autoimmunity, Immunological Reviews, in press.

Mahajan V, Mattoo H, Deshpande V, Pillai S, Stone JH. IgG4-related disease. Annual Review of Pathology. 9, 315-47, 2014.

Mattoo H, Mahajan VS, Della-Torre E, Sekigami Y, Carruthers M, Wallace ZS, Deshpande V, Stone JH, Pillai S, De novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG4-related disease. J Allergy Clin Immunol, 2014.

Pillai S. Rethinking Mechanisms of Autoimmune Pathogenesis. Journal of Autoimmunity. 45, 97-103, 2013.

Pillai S, Netravali I, Cariappa A, Mattoo H. Siglecs and Immune Regulation. Annual Review of Immunology. 30:357-392, 2012.

Pillai S, Mattoo H, Cariappa A. The role of B cells in autoimmunity. Current Opinion in Immunology.
23:721-731, 2011.

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, Pillai S. Functionally defective germline variants of sialic acid acetylesterase in autoimmunity. Nature. 466;244-247, 2010.

Contact

Contact Us

Pillai Laboratory

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

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