Epigenetic reprogramming with Mixed Lineage
Leukemia core complex inhibitors
Dr. Michael Cosgrove, Associate Professor, Departments of Biochemistry
and Molecular Biology, Upstate Medical University
ABSTRACT
Cell identity depends on enzymes that regulate the degree of histone
H3 lysine 4 (H3K4) methylation. We study a multi-protein complex that
is crucial for normal human development and homeostasis called the
Mixed Lineage Leukemia (MLL) core complex. The MLL core complex
catalyzes mono-, di- and trimethylation of H3K4, activities that are
required for normal stem cell differentiation programs such as
hematopoiesis and postnatal neurogenesis. Activating and inactivating
mutations in MLL1 are associated with aggressive infant leukemias and
other cancers, suggesting that the activity of MLL is under tight control. We have discovered a novel
class of molecules that regulate cellular H3K4 methylation levels through inhibition of the MLL core
complex. We are developing this technology for cell type and locus specific epigenetic reprograming of
mammalian cells and for treatment of MLL associated malignancies.
BIOGRAPHY
Dr. Cosgrove is an Associate Professor in the Department of Biochemistry and Molecular Biology at
SUNY Upstate Medical University. He received his Ph.D. degree in biochemistry from Syracuse University
in 1998, doing thesis work with H. Richard Levy on the structure and function of glucose metabolizing
enzymes. This work included spending a semester abroad working with Margaret Adams in the
laboratory of Molecular Biophysics at Oxford University. After a postdoctoral fellowship at Cornell
University, he did further postdoctoral research in the laboratory of Cynthia Wolberger at the Johns
Hopkins School of Medicine, on the crystal structure analysis of chromatin proteins.
Dr. Cosgrove’s research focuses on the molecular mechanisms by which genes are activated by enzymes
that regulate chromatin structure. His laboratory recently made significant discoveries that advance our
understanding of how an enzyme called the Mixed Lineage Leukemia protein works. He is using this
information to design potential drugs for the treatment of leukemia and other cancers. Dr. Cosgrove
has received New Investigator awards from the March of Dimes Birth Defects Foundation, the Leukemia
Research Foundation, and he has been named an American Cancer Society Research Scholar. His
research has received funding from the March of Dimes and Leukemia Research Foundations, the
American Cancer Society, and the National Cancer Institute of the National Institutes of Health.