We study molecular control of immune system development and immune function

Systemic Autoimmunity

Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) are characterized by autoreactivity to nuclear antigens including ribonucleoproteins and DNA. The lab is studying the mechanisms of anti-DNA responses, which are prevalent and pathogenic in SLE. In particular, we have defined extracellular nuclease DNASE1L3 as an essential gatekeeper of tolerance to self-DNA, and are currently characterizing mechanisms whereby its disruption facilitates anti-DNA responses in SLE.

Dendritic Cells

Dendritic cells (DCs) are key sentinel cells that comprise the antigen-presenting classical DCs (cDCs) and interferon-producing plasmacytoid DC (pDCs). The lab has identified several key transcriptional regulators and signaling pathways that control the DC lineage, such as the "master regulator" of pDC development (Tcf4/E2-2), the driver of cDC differentiation in the periphery (Notch2) and the key “pan-DC” regulator (Trim33). We are using these genetic insights to better characterize the role of DCs in immune response to infections, immune homeostasis and autoimmunity.

Immune System Development In Unmanipulated Animals

The majority of immune cels including DCs are being continuously generated from hematopoietic stem cells (HSCs) in the adult bone marrow. The lab has been using genetic tools to characterize immune cell development from endogenous HSCs, including its kinetics and clonal composition in unmanipulated animals. We are currently characterizing the abnormalities of HSC-driven immune development that are associated with inflammation, aging or malignant transformation.