New Investigator Research Grant Program

Our research focuses on a devastating blood cancer called MLL-rearranged (MLLr) acute myeloid leukemia (AML), an aggressive disease with poor prognosis. This cancer is driven by a genetic change that produces an abnormal MLL fusion protein. MLL fusions hijack two other proteins, LEDGF and Menin, and together they activate genes that promote leukemia growth. A major advance in treating MLLr AML has been the development of Menin inhibitors, which block the interaction between MLL fusions and Menin. Although these drugs show strong anti-leukemic effects and have received regulatory approval, many patients eventually relapse and do not survive five years after diagnosis. Because LEDGF tethers MLL fusions and Menin to oncogenic genes, understanding exactly how LEDGF supports MLLr leukemia will provide new opportunities to address the cancers that stop responding to Menin inhibitors. Notably, removing LEDGF can stop leukemia cell growth while sparing healthy blood cells, making it an attractive therapeutic target. To define LEDGF’s direct roles, we will examine what happens immediately after it is removed from MLLr leukemia cells. Using advanced chemical methods, we can eliminate LEDGF in under an hour and capture early molecular changes. We will also use imaging to visualize how LEDGF regulates MLL fusions in the nucleus. This work will clarify mechanisms of resistance and uncover new vulnerabilities, with the goal of preventing relapse and improving patient survival.