The Gomez lab studies the functional role of epigenetic and transcriptional mechanisms in controlling fundamental properties of vascular smooth muscle cells. Using a combinatorial approach of epigenomic (Cut&Tag, ATACseq), transcriptomic (RNAseq), and functional studies, we aim to characterize the causal relationship between chromatin states or non-coding RNA signatures establishment and maintenance of vascular cell lineage identity and functions. Identifying and understanding such mechanisms is particularly relevant considering the inherent phenotypic plasticity of vascular smooth muscle cells and their ability to react to changes in their environment dynamically. Vascular smooth muscle cells are highly specialized contractile cells responsible for maintaining vascular integrity and control of the vascular tone. However, during an adaptive or maladaptive response to environmental cues, smooth muscle cells can profoundly alter their contractile phenotype and undergo a dedifferentiation process called “phenotypic switching” characterized by the loss of expression of the smooth muscle lineage gene repertoire and the concomitant enhancement in their ability to proliferate, migrate or produce extracellular matrix. In some instances, including adaptive vascular remodeling, smooth muscle cells can re-differentiate into contractile cells after transient phenotypic switching indicating persistence in lineage identity. Our lab is particularly interested in the epigenetic mechanisms (histone modifications, DNA methylation) guaranteeing the retention of smooth muscle cell lineage identity and their functional relevance during vascular development, remodeling, and diseases. We develop novel tools to perform gene-specific epigenetic editing in vitro and in vivo. We utilize these tools in smooth muscle cell fate mapping mice to determine the role of lineage-specific epigenetic programming in controlling cell identity, lineage memory, differentiation, and plasticity during blood vessel formation, acute vascular injury-repair processes, and chronic vascular diseases such as aortic aneurysm, hypertension, atherosclerosis, and peripheral artery disease.
- Epigenetic control of vascular smooth muscle cell function and microvascular remodeling in peripheral artery disease
- Intersection and interdependence of epigenetic mechanisms in vascular cells
- Identification of new functionally relevant non-coding RNAs regulating SMC functions
- Relationship between epigenetics and mechanotransduction