Ongoing Research Projects
Overall Lab Strategy
Endothelial cells line all the blood vessels of the body and are a critical interface that communicates changes in blood composition (oxygen, glucose, lipids and metabolites) with all major organs of the body. We study the molecular and cellular biology of endothelial cells and have applied this information to the physiology and pathophysiology of inflammation and diseases such as atherosclerosis and hypertension. Our experimental systems utilize a wide variety of techniques spanning from single molecule approaches, protein biochemistry, structural biology, cell biology to integrated function using genetic models of disease.
Present Projects Include
Model of LDL transcytosis
1. Elucidating the role of low density lipoprotein (LDL) transcytosis as a driver of atherosclerosis using mouse genetics, biochemical mapping of protein-protein interactions of LDL with novel binding proteins and antibody development to antagonize the pathways. (above)
Inflammatory cytokines regulate cholesterol synthesis
2. Examining the role of caveolin-1, LDL receptor and the sterol responsive transcription factor (SREBP2 interfacing with cellular energetics and inflammation using RNA seq, lipidomics, metabolomics and flux approaches (above).
3. Defining the role of endothelial nitric oxide synthase (eNOS) in the development of heart failure and exercise intolerance and regulation of eNOS by plasminogen activator inhibitor-1. (above)
Cis-prenyltransferase (cis-PTase) catalyzes the condensation of 5-carbon isopentenyl diphosphate (IPP) with an allylic diphosphate
In addition to our focus in the cardiovascular system, we discovered an evolutionarily conserved enzyme(cis-prenyltransferase) that generates dolichol, the essential lipid for all protein glycosylation reactions in the endoplasmic reticulum. Mutations of this gene are linked to retinitis pigmentosa, type 2 diabetes, epilepsy and movement disorders. We are performing structural and biochemical analysis and mouse genetic studies are ongoing to assess enzyme regulation and function, respectively. (above)