Grant: Foundation Grant

Circulating in the blood is a myriad of cells with different functions that are critical for our health, including red blood cells that carry oxygen, platelets that help to stop bleeding and immune cells that fight off infections and cancers. These circulating blood cells are not immortal, but rather are constantly being renewed by a continuous repetition of the process that led to their initial specialization. In this complex process, banks of genes are turned on and off in precursor cells to "steer" their differentiation toward one specialized cell type or another. This occurs primarily through the action of proteins called transcription factors, which reside in the cell nucleus and can regulate the activity of thousands of genes simultaneously. Not surprisingly, mistakes sometimes occur in this complex process and can lead to a number of very serious diseases. My own research has focused on identifying the critical components in normal blood cell differentiation and in characterizing the molecular defects that lead, in particular, to bleeding disorders and blood-borne cancers such as leukemia and lymphoma. Over 20 years ago, I co-discovered two transcription factors (Gfi1 and Gfi1b) and was the first to determine the role of Gfi1 in blood diseases including leukemia. More recently, I discovered the role of another transcription factor and co-factor of Gfi1, called Miz-1, in blood cell formation and leukemia. My goal is to understand how key blood formation processes are controlled on a molecular level and how deficiencies in these processes that lead to diseases can be fixed. Over the next few years, we will bring together clinical expertise and the most advanced biomedical research techniques to address two blood cancers: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) as well as inherited platelet disorders (IPD) that lead to blood clotting problems.