Grant: Operating Grant

The cells of our blood and immune system are produced in the bone marrow, from a small population of hematopoietic stem cells, in the process of cell division and differentiation known as hematopoiesis. Hematopoiesis requires precise regulation of gene expression and efficient repair of DNA damage, and its disruptions result in many life-threatening disorders. In recent work we and others demonstrated the essential role of protein MYSM1 in the process of hematopoiesis (Nijnik et.al., Blood 2011; Jiang. et.al., Immunity 2011). MYSM1 binds DNA and catalyzes the removal of ubiquitin from a DNA-packaging protein Histone H2A. MYSM1 therefore functions to organize the DNA in our cells, controlling gene expression and potentially also DNA repair. The proposed research program will characterize the functions of MYSM1 at different stages of hematopoietic process and the molecular mechanisms of its activity. This will enhance our knowledge of the fundamental biology of hematopoiesis, blood, and immune systems, and in the long-term may contribute to better understanding and treatment of hematological disorders.