Major areas of research in the lab include:

Stem cells in normal hematopoiesis and leukemia

Stem cells manifest a unique capacity to differentiate into various cell types while maintaining their own number in an undifferentiated state. Thus, a single hematopoietic stem cell (HSC) can regenerate the entire blood system, enabling the life-saving bone marrow transplantation procedure. Paradoxically, the role and properties of HSC during normal blood production (hematopoiesis) in unirradiated organisms remain controversial. We have developed genetic systems that identify and trace HSC, and showed that these cells are indeed a major source of adult hematopoiesis. Current studies are focused on the mechanisms of HSC differentiation in normal conditions and their subversion in leukemia.

Dendritic cell development and function

Dendritic cells (DC) detect, capture and "present" invading pathogens to lymphocytes, thus representing a critical link between the innate and adaptive immunity. Dendritic cells include several lineages dedicated to distinct pathogens and immune response types, including the classical DCs (cDCs) and interferon-producing plasmacytoid DC (pDCs). Our studies have identified several transcription factors and signaling pathways that control the development and specification of DCs. 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 I diabetes, multiple sclerosis and systemic lupus erythematosus (SLE). We are studying the mechanisms of autoimmune responses focusing on SLE, in which self-DNA and RNA are being targeted by the immune system. Recently, we have characterized a unique nuclease, DNASE1L3, as an essential mechanism of tolerance to self-DNA whose loss causes SLE-like autoimmunity focused on self-DNA. We are exploring the mechanism of DNASE1L3 activity and its potential as a therapeutic tool.