1) Heart DevelopmentWe pursue mouse genetic-based projects focused on understanding the contributions of 1) the BAF chromatin remodeling complex and 2) Wnt signaling to heart valve development and disease. Both projects characterize cellular and molecular origins of heart valve phenotypes that manifest in a collection of transgenic mouse models we have developed. From these observations, we determine origins and progression of congenital valve defects that affect up to 5% of humans. We also define molecular connections between the BAF complex and Wnt and other pathways and identify key target genes using candidate gene and transcriptome approaches. Additional heart development projects are studying mechanisms of myocardial trabeculation and the contributions of chromatin regulators to cardiac specification. This latter work includes zebrafish genetics research, which emerged as a field here at the University of Oregon.
2) Organ RegenerationIn collaboration with Scott Stewart, we use zebrafish as a model to determine roles of cell signals and chromatin reprogramming during vertebrate regeneration. Unlike humans, zebrafish possess the remarkable ability to perfectly regrow lost appendages (and other organs, including the heart). We intend to uncover the keys to zebrafish regeneration to inspire logical approaches to enhance mammalian organ repair. As an example, we showed how two signaling pathways (Wnt and BMP) direct formation of de-differentiated bone progenitors upon caudal fin amputation and then balance simultaneous needs for those cells to proliferate and re-differentiate into replacement bone cells. We are pursuing how additional pathways are integrated into this network and how the signals cooperate with chromatin regulators to “switch” gene expression programs that promote transitions between progenitor-like and differentiated states.
3) Chemical Genetic Technologies for Gene Regulation StudiesWe collaborate closely with Chris Doe’s lab developing the “TU-tagging” technology to label newly synthesized RNA transcripts in specific cell types in mice, which are then purified and analyzed by RNA-Seq. Our initial TU-tagging studies identified novel heart and vasculature expressed genes whose developmental functions and regulation we are studying. Further, we are optimizing TU-tagging to expand its utility while applying the method to answer questions about dynamic gene regulation during organogenesis and regeneration.
(pulled from pubmed)