Signaling, LncRNAs, and Genome Regulation
Signaling pathways integrate extracellular signals to productively reprogram genomic expression. With respect to signaling, the lab focuses on essential pathways in epidermal stem cell differentiation and cancer. These include the Ras-Raf-Mek-Erk MAPK pathway and its interactions with other specific pathways, including those involving PI3K, Notch, and WNT. Work in the lab has been the first to knockout the Ras-Raf-Mek-Erk MAPK pathway in mammals [Developmental Cell (2007)] to demonstrate its essential role in tissue homeostasis, the first to define the genomic programs induced in early cancer progression triggered by oncogenic Ras activation [Cancer Cell (2009)]as well as the first to characterize the dependence of the pathway on the IQGAP1 scaffold in cancer [Nature Medicine (2013)].
In the case of long-noncoding RNAs (lncRNAs), the lab discovered the first lncRNAs involved in somatic stem cell differentiation, including the ANCR stem cell lncRNA [Genes & Development (2012)] and the terminal differentiation lncRNA, TINCR [Nature (2013)]. Discovery and integration of new roles for signaling networks, epigenomic modifiers, TFs, and lncRNAs is a major focus of the lab designed to define essential regulators of stem cell differentiation and cancer.
For genome regulation, the lab focuses on how essential TFs and lncRNAs interact with regulators of DNA methylation and chromatin to control genome expression in stem cell differentiation and cancer. Work in the lab was the first to demonstrate an essential role for DNA methyltransferases [Nature (2010)] and for the EZH2-JMJD3 histone methyltransferase-demethylases [Genes & Development (2008)] in tissue homeostasis. The lab has also identified TFs with new roles in stem cell differentiation, including ZNF750 [Developmental Cell (2012), Genes & Development (2014)] and MAF/MAFB (Developmental Cell (2015)].