Alan C. Mullen, MD, PhD
Our research is focused on understanding the cell-type-specific responses to TGF-beta signaling in development and disease. TGF-beta signaling regulates diverse process from normal development, wound healing and tissue homeostasis to tumor formation, fibrosis and metastasis. Canonical TGF-beta signaling is mediated through activation of the transcription factors Smad2 and Smad3, which bind DNA in association with other transcription factors to regulate gene expression. Numerous cell types in the human body respond to TGF-beta signaling, but each cell type sees a largely unique pattern of Smad2/3 occupancy across the genome. This unique pattern of Smad2/3 occupancy results in a cell-type-specific response to TGF-beta signaling and regulates transcription of both coding and long noncoding RNAs. We use a combination of genomics, genetics and biochemistry to study how TGF-beta signaling regulates coding and long noncoding genes in endodermal development and in hepatic fibrosis and how these networks of coding and long noncoding RNAs regulate cell fate decisions.