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Read the Pillai Lab 2017-2018 Annual Report
Shiv Pillai, MD, PhDProfessor of MedicineHarvard Medical School
Associate GeneticistCenter for Cancer Research
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 lupus, 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.
Shiv Pillai MD, PhDPrincipal Investigator
* PhD Candidate
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 (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
Fraschilla I, Pillai S. Viewing Siglecs through the lens of tumor immunology. Immunol Rev. 2017 Mar;276(1):178-191.
Mattoo H, Stone JH, Pillai S. Clonally expanded cytotoxic CD4(+) T cells and the pathogenesis of IgG4-related disease. Autoimmunity. 2017 Feb;50(1):19-24.
Yuen GJ, Demissie E, Pillai S. B lymphocytes and cancer: a love-hate relationship. Trends Cancer. 2016 Dec;2(12):747-757.
Mattoo H, Mahajan VS, Maehara T, Deshpande V, Della-Torre E, Wallace ZS, Kulikova M, Drijvers JM, Daccache J, Carruthers MN, Castelino FV, Stone JR, Stone JH, Pillai S. Clonal expansion of CD4(+) cytotoxic T lymphocytes in patients with IgG4-related disease. J Allergy Clin Immunol. 2016 Sep;138(3):825-38.
Mahajan VS, Demissie E, Mattoo H, Viswanadham V, Varki A, Morris R, Pillai S. Striking Immune Phenotypes in Gene-Targeted Mice Are Driven by a Copy-Number Variant Originating from a Commercially Available C57BL/6 Strain. Cell Rep. 2016 May 31;15(9):1901-9.
Mahajan VS, Pillai S. Sialic acids and autoimmune disease. Immunol Rev. 2016 Jan;269(1):145-61.
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