Transcriptional enhancers, eRNAs, and molecular control of early mammalian development. During the development of mammals from a single fertilized egg, there are rapid changes in both the number and types of cells present.  The earliest types of cells which give rise to the embryo proper are termed pluripotent, because of their ability to differentiate into all three primitive germ layers.  Using these pluripotent cells from mice, we can investigate how these cells differentiate into all the different cell types.  In particular, our lab is focused on how different enhancers work collaboratively to regulate gene expression in normal pluripotent cells but also as they differentiate.  Second, we focus on how the eRNAs which arise from highly active enhancers may regulate gene expression.

The molecular mechanism of cohesin complex mutations in cancer. The cohesin complex plays a central role in gene expression by facilitating and stabilizing chromatin loops which permits enhancers to be brought into close physical proximity of the genes they regulate within the nucleus. Importantly, mutations within core cohesin complex subunits (STAG2, SMC3, SMC1A, RAD21) are found in 10-20% of patients with Acute Myeloid Leukemia (AML).  Our lab is focused on understanding how these mutations promote leukemia development, but also how they interact with own known leukemic drivers.