Research > Faculty By Division > Deepta Bhattacharya, PhD
|Research in the Bhattacharya lab focuses on molecular approaches to direct B cell differentiation to establish immunity to infectious disease, and stem cell differentiation for regenerative medicine. Current projects in the lab include:
1) Understanding the cellular and molecular basis of antibody-mediated immunity to variable viruses. After infection or vaccination, B cells that recognize the pathogen proliferate and undergo a massive level of expansion. Upon clearance of the infection a small fraction of the "best" B cells are retained to become memory B cells or long-lived plasma cells. Our recent work has established that memory B cells are excellent at recognizing not only the original pathogen, but also mutant escape variants of the pathogen. In contrast, long-lived plasma cells are highly specific only for the original pathogen. We are studying the transcription factors that regulate the memory B cell vs. long-lived plasma cell fate, and are studying mechanisms to alter this fate to provide effective immunity against mutable viruses such as influenza and Dengue.
2) Engineering human induced pluripotent stem cells to generate antibody-mediated immunity. A small fraction of patients infected with HIV or dengue virus, or vaccinated against influenza develop remarkable antibodies that neutralize nearly all clinical isolates of these viruses. Yet it is unclear how to induce these types of antibodies in the broader population through standard vaccination. Using novel targeted nuclease technologies, we are engineering human iPS cells to express these antibodies and differentiating them into transplantable long-lived plasma cells. The long-term goal of this project is to provide permanent immunity to recipients of these engineered plasma cells.
3) Identifying novel G-protein coupled receptors that regulate hematopoietic stem cell self-renewal and differentiation. The adult stem cell precursor to B cells and all other blood lineages is the hematopoietic stem cell. These hematopoietic stem cells are the only types of stem cells in routine clinical use to date, largely because they can home back to the proper bone marrow environment if injected intravenously. The mechanisms by which these cells find their way to the proper niche to self-renew or differentiate are unknown. We are using genetic approaches to identify novel orphan G-protein coupled receptors and chemokine receptors that guide hematopoietic stem cells to their proper niches.
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|Becker, A.M., Michael, D.G., Satpathy, A., Sciammas, R., Singh, H., and Bhattacharya, D.. IRF-8 extinguishes neutrophil potential and promotes dendritic cell lineage commitment in both myeloid and lymphoid mouse progenitors.. Blood, 119, 2003-2012., 2012 Abstract|
|Purtha, W.E., Swiecki, M., Colonna, M., Diamond, M.S., and Bhattacharya, D.. Spontaneous mutation of the Dock2 gene in Irf5-/- mice complicates analysis of type I interferon production and antibody responses.. Proc Natl Acad Sci U S A, 109, E898-904., 2012 Abstract|
|Purtha W.E., Tedder T.F., Johnson S., Bhattacharya D.*, and Diamond M.S.*.. Memory B cells, but not long-lived plasma cells, possess antigen specificities for viral escape mutants.. J Exp Med, 208, 2599-2606., 2011 Abstract|
|Inlay, M.A.*, Bhattacharya, D.*, Sahoo, D., Serwold, T., Seita, J., Karsunky, H., Plevritis, S.K., Dill, D.L., and Weissman, I.L.. Ly6d marks the earliest stage of B cell specification and identifies the branchpoint between B and T cell development. Genes Dev, 23, 2376-2381., 2009 Abstract|
|Bhattacharya, D.*, Czechowicz, A.*, Ooi, A.G., Rossi, D.J., Bryder, D., and Weissman, I.L.. Niche recycling through division-independent egress of hematopoietic stem cells. J Exp Med 206, 2837-2850., 2009 Abstract|
|Czechowicz, A., Kraft, D., Weissman, I.L.*, and Bhattacharya, D*. Efficient transplantation via antibody-based clearance of hematopoietic stem cell niches. Science 318, 1296-1299., 2007 Abstract|
|Bhattacharya, D., Cheah, M.T., Franco, C.B., Pin, C.L., Sha, W.C., and Weissman, I.L. Transcriptional profiling of antigen-dependent murine B cell differentiation and memory formation. J Immunol 179, 6808-6819., 2007 Abstract|
|Bhattacharya, D., Rossi, D.J., Bryder, D., and Weissman, I.L. Purified hematopoietic stem cell engraftment of rare niches corrects severe lymphoid deficiencies in unconditioned hosts. J Exp Med 203, 73-85., 2006 Abstract|
|Bhattacharya, D.*, Bryder, D.*, Rossi, D.J., and Weissman, I.L. Rapid lymphocyte reconstitution of unconditioned immunodeficient mice with non-self-renewing multipotent hematopoietic progenitors. Cell Cycle 5, 1135-1139., 2006 Abstract|
|Luckey, C.J.*, Bhattacharya, D.*, Goldrath, A.W.*, Weissman, I.L., Benoist, C., and Mathis, D. Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells. Proc Natl Acad Sci U S A 103, 3304-9., 2006 Abstract|