The immune system comprises hundreds of highly specialized cell types that collectively protect us from infection while tolerating our own body. We are interested in the process whereby this amazing diversity is generated from a single source, the hematopoietic stem cell (HSC). We are applying genetic tools to understand normal HSC function and its subversion during malignant transformation leading to leukemia. Among the immune cell types, one of our favorites is the plasmacytoid dendritic cell (pDC) – an antiviral defense specialist and a key immune weapon against SARS, MERS and similar viruses. Conversely, aberrant activation of pDCs and other dendritic cell types may facilitate the breakdown of tolerance and the resulting autoimmunity. We are studying the development of dendritic cells, their function during immune responses and their malfunction in autoimmune diseases such as systemic lupus erythematosus.