Research Abstract:
My laboratory employs immunological, cell biological, and functional genomics approaches to gain insight into the diverse mechanisms by which fate decisions are made within the hematopoietic system. We are particularly interested in three aspects of hematopoietic and immunological development: 1) the control of quiescence vs. proliferation in hematopoietic stem cells (HSCs); 2) the transcriptional pathways that direct the common lymphoid progenitor (CLP) to differentiate into the B cell and dendritic cell lineages; 3) the intrinsic signals that allow for the formation and self-renewal of memory B cells.
HSCs undergo cellular divisions only rarely under normal conditions. However, HSCs begin to divide rapidly when placed into irradiated environments or other settings in which there are hematopoietic deficiencies, presumably to mediate hematopoietic recovery. Through proteomic and genetic approaches, my lab is interested in identifying both the cell-intrinsic and extrinsic cues that trigger HSCs to divide.
As HSCs differentiate, some cells diverge into the lymphoid pathway through the generation of CLPs. These progenitors can generate cells of the lymphoid pathway, but not myeloid, erythroid, or megakaryocytic cells. My lab is interested in the transcriptional mechanisms and gene regulatory networks that direct CLPs to differentiate into B cells, T cells, dendritic cells, and natural killer cells. We use a combination of prospective isolation of lineage-restricted progenitors, functional genomics, and genetic manipulations to study these decisions.
Although the ability to self-renew is progressively lost during the immediate stages of differentiation downstream of the HSC, this ability is regained at the diametric opposite end of the hematopoietic developmental spectrum in memory lymphocytes. Memory B cells, like HSCs, have the capacity to self-renew for life and can give rise to more short-lived progeny upon antigenic re-encounter. My lab is using microarray-based functional genomics approaches to understand how memory B cells are generated and how they maintain themselves for life, both of which are critical to the development of effective vaccines.
Selected Publications:
Inlay MA*, Bhattacharya D*, Sahoo D, Serwold T, Seita J, Karsunky H, Plevritis SK, Dill DL and Weissman IL. Ly6d marks the earliest stage of B cell specification and identifies the branchpoint between B and T cell development. Genes Dev 2009 (In Press).
Bhattacharya D, Ehrlich LI and Weissman IL. Space-time considerations for hematopoietic stem cell transplantation. Eur J Immunol 2008 38: 2060-2067.
Czechowicz A, Kraft D, Weissman IL* and Bhattacharya D*. Efficient transplantation via antibody-based clearance of hematopoietic stem cell niches. Science 2007 318: 1296-1299.
Bhattacharya D, Cheah MT, Franco CB, Pin CL, Sha WC and Weissman IL. Transcriptional profiling of antigen-dependent murine B cell differentiation and memory formation. J Immunol 2007 179: 6808-6819.
Bhattacharya D, Rossi DJ, Bryder D and Weissman IL. Purified hematopoietic stem cell engraftment of rare niches corrects severe lymphoid deficiencies in unconditioned hosts. J Exp Med 2006 203: 73-85.
Last Updated: 09/14/2009 |