Our lab is interested in blood vessel and lymphatic vessel development. Proper assembly and maintenance of these vascular networks is critical for embryonic survival and adult health. We believe identifying genes that influence vascular development will present new therapeutic options for the treatment of pathological vascular disorders.
In order to identify and study genes involved in vascular development, we exploit ATP-dependent chromatin-remodeling complexes (CRCs). These complexes utilize energy derived from ATP hydrolysis to temporarily unravel and reorganize chromatin, thereby making DNA more accessible to proteins that positively or negatively modulate transcription. CRCs act selectively on the genome to regulate expression of specific target genes and can coordinate regulation of multiple genes to influence precise developmental programs. For these reasons, we believe CRCs present unique opportunities for identifying genes that mediate vascular development and for elucidating their functions.
Each CRC contains a central ATPase catalytic subunit that is required for its assembly and function. In order to study the role of CRCs in vascular development, we genetically delete these catalytic subunits in endothelial cells and look for resulting vascular phenotypes in mutant mice. We then use candidate and unbiased approaches to backtrack and identify misregulated CRC target genes that contribute to the vascular phenotypes. Our Research page describes focus areas that have arisen in the lab using this novel approach to study vascular development.
Finally, we are fortunate to work in a stimulating intellectual environment within the Cardiovascular Biology Research Program at OMRF. The Program is comprised of eight labs, which are all investigating various aspects of blood and vascular biology. Several of our colleagues share our interest in vascular development, and our interactions with them enrich our research.