Research Summary
The overall goal of Dr. Cowley’s research program is to understand, at the epigenetic and molecular levels, how exposure to environmental stressors during development programs susceptibility to metabolic disease in later life. By understanding these mechanisms, he hopes to identify novel targets for therapeutic intervention that could protect against environmentally induced disease. One of the central hypotheses is that imprinted genes – defined by their expression from only one of their two parental alleles – play a central role in this process. His lab integrates data from mouse models, cell culture systems, and human samples to understand how imprinted genes respond to developmental stress and to elucidate the molecular mechanisms through which they drive disease. His group identified a transcriptional network of imprinted genes, driven by the transcription factor Zac1, that is activated in hepatocytes of young mice in response to adverse developmental environments. Using a combination of in vivo and in vitro models, they showed that hepatocyte-specific activation of Zac1 and the imprinted gene network is sufficient to drive metabolic dysfunction-associated steatotic liver disease (MASLD). They have begun to elucidate the molecular and cellular mechanisms through which this network acts to disrupt hepatic lipid homeostasis and drive fibrotic transformation of hepatocytes.
CGIBD Focus Area(s): Regeneration and Repair
Pilot and Feasibility Award 2019
Collaborators: Diehl
