Research
Our research is focused on understanding the molecular mechanisms of epigenetic gene regulation. Epigenetics is a field of biology that strives to understand how cells inherit information that is independent of changes in DNA sequence. We are focusing on the molecular mechanisms that regulate histone H3 lysine 4 (H3K4) methylation, an epigenetic mark associated with transcriptional activation. H3K4 methylation is catalyzed by the Mixed Lineage Leukemia (MLL) family of enzymes, which are frequently altered in aggressive acute lymphocytic and myeloid leukemias in infants and adults. The genes encoding MLL family enzymes are also altered in human developmental disorders such as Kabuki Syndrome, Weidman-Steiner Syndrome, and Kleefstra Syndrome. In addition, MLL family enzymes are mutated in non-Hodgkin lymphomas, pediatric medulloblastomas, lung, renal, and prostate carcinomas.
MLL family enzymes interact with an evolutionarily conserved group of proteins that include WDR5, RbBP5, Ash2L and DPY-30 (WRAD). We have developed an experimental reconstitution system that has allowed us to dissect the molecular mechanisms of H3K4 methylation by MLL family complexes. We are using this system to address questions about complex formation, mechanism of multiple lysine methylation, and inhibitor design.
MLL family enzymes interact with an evolutionarily conserved group of proteins that include WDR5, RbBP5, Ash2L and DPY-30 (WRAD). We have developed an experimental reconstitution system that has allowed us to dissect the molecular mechanisms of H3K4 methylation by MLL family complexes. We are using this system to address questions about complex formation, mechanism of multiple lysine methylation, and inhibitor design.