Major areas of research in my lab include stem cells in normal hematopoiesis and leukemia, dendritic cell development and function, and mechanisms of autoimmunity.
Stem Cells in Normal Hematopoiesis and Leukemia
Stem cells can both differentiate into various cell types and maintain their own population of undifferentiated cells. Thus, a single hematopoietic stem cell (HSC) can regenerate the entire blood system in irradiated recipients, enabling a potentially life-saving bone marrow transplantation. However, controversies remain on the role and properties of HSCs during normal blood production—hematopoiesis—in unirradiated organisms.
We have developed genetic tools to identify and trace HSCs, and we have shown that these cells are indeed a major source of adult hematopoiesis. Our current studies focus on the mechanisms of HSC differentiation in normal conditions and their subversion in leukemia.
Dendritic Cell Development and Function
Dendritic cells (DCs) detect, capture, and present invading pathogens to lymphocytes, thus representing a critical link between innate and adaptive immunity. DCs encompass several lineages dedicated to distinct pathogens and immune response types, including the antigen-presenting classical DCs (cDCs) and interferon-producing plasmacytoid DCs (pDCs).
Our studies have identified several transcription factors and signaling pathways that control the development and specification of DCs. Our current studies focus on the molecular control of DC function in the steady state and during immune responses.
Mechanisms of Autoimmunity
Aberrant recognition and attack of the body by its own immune system causes autoimmune diseases such as type 1 diabetes, multiple sclerosis, and systemic lupus erythematosus (SLE). We are studying the mechanisms of autoimmunity by focusing on SLE, in which the immune system targets self-DNA and self-RNA. We have characterized a unique nuclease, DNASE1L3, as an essential mechanism of tolerance to self-DNA, the loss of which causes SLE-like autoimmune responses towards self-DNA. We are exploring the mechanism of DNASE1L3 activity and its potential as a therapeutic tool.
Professor, Department of Pathology
Professor, Department of Medicine
Co-Director, Judith and Stewart Colten Center for Autoimmunity
PhD from Weizmann Institute of Science
Journal of experimental medicine. 2018 Sep 03; 215(9):2265-2278
Frontiers in immunology. 2018 Jul 04; 9:1482-1482
Cell reports. 2018 Jun 19; 23(12):3658-33672.e6
Experimental hematology. 2018 May 05; 61:26-35
Notch signaling facilitates in vitro generation of human IRF8-dependent CLEC9A+classical dendritic cells [Meeting Abstract]
European journal of immunology. 2018 MAY; 48:164-164
Immunology & cell biology. 2018 Mar 23;
Notch Signaling Facilitates In Vitro Generation of Cross-Presenting Classical Dendritic Cells
Cell reports. 2018; (),(2018):
Immunity. 2017 Mar 21; 46(3):504-515