Research & Publications
Our laboratory is interested in the role of microdomains in regulating the fidelity of signal transduction in vascular endothelial cells using a variety of cell biological, molecular and biochemical techniques and genetic models in vivo. We are interested in how growth factors and mechanical stress couples to activation of nitric oxide synthesis via phosphorylation and protein-protein interactions. We also are studying how vascular endothelial cells process lipids such as triglycerides and cholesterol and are defining novel pathways that regulate lipid uptake and metabolism. Finally, we have identified the primary mechanism of how mammalian cells generate lipids required for protein glycosylation reactions and are committed to elucidate the structural basis of this conserved enzyme system.
Extensive Research Description
The vascular endothelium is the largest endocrine organ in the body, at the interface of blood and tissue. As such, many common diseases such as atherosclerosis, heart disease, cancer, macular degeneration and diabetes have a common signature of endothelial cell dysfunction. Our laboratory is focused on understanding the etiology of vascular dysfunction in these diseases and is focused on several broad aspects of endothelial cell biology and function.
We are exploring multiple avenues of research with a critical eye towards discovering new, biologically relevant therapeutic targets and pathways.
1. Elucidation how endothelial NOS (eNOS) is regulated in the context of normal physiology and in disease using cellular and molecular approaches in signal transduction. Particular areas are the study of cholesterol enriched plasmalemmal microdomains, caveolins, cavins, and downstream pathways.
2. Identification of new pathways that mediate the uptake and transcytosis of low density lipoprotein (LDL) and determining how LDL receptor influences vascular disease.
3. Proteomic analysis of protein phosphorylation using optogenetic approaches;
4 NgBR structure function and cellular biology in cholesterol metabolism and protein N-glycosylation;
We typically use basic molecular and cellular approaches and apply our findings to complex genetic systems (compound mutant mouse strains) to study blood vessel structure and function in physiology and disease.
Cardiovascular Diseases; Cell Membrane Permeability; Circulatory and Respiratory Physiological Phenomena; Neoplasms; Chemicals and Drugs