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
PhD from Weizmann Institute of Science
Immunity. 2017 Mar 21; 46(3):504-515
Immunity. 2016 Dec 13; 46(1):65-77
Cancer cell. 2016 Nov 14; 30(5):764-778
Immunity. 2016 Sep 20; 45(3):597-609
Cell. 2016 Jun 30; 166(1):88-101
Journal of experimental medicine. 2016 Mar 07; 213(3):415-431
Immunity. 2015 Aug 18; 43(2):277-288
Journal of experimental medicine. 2014 Sep 22; 211(10):1969-1976