Research

Cardiovascular disease is responsible for 18 million deaths each year worldwide, and across the globe the lives of over 460 million are threatened by type 2 diabetes. Endothelial cells make up the single cell lining of larger blood vessels, and are the sole cell type found in capillaries, and they dictate vascular function and macromolecule exchange between the blood and the tissues. The overall goal of our laboratory is to discover the processes in endothelial cells that govern cardiovascular and metabolic health and disease. Striving to have transformative impact on our understanding of conditions that threaten the well-being of millions, we focus our attention on molecules associated with the endothelial cell plasma membrane and how they dictate the responses of the endothelium to extracellular cues. Our mission is to identify novel targets for new preventative and treatment strategies against cardiovascular disease and type 2 diabetes. To meet that mission we employ state-of-the-art techniques in human and mouse genetics, and in cell and molecular biology, and disease models in mice.

Major Contributions to Endothelial Cell Biology

• Discovered that eNOS is targeted to caveolae/lipid rafts where it resides in a signaling module.
• Discovered a caveolae/raft subpopulation of estrogen receptors (ER) in endothelial cells that invokes non-nuclear signaling that affords protection from vascular injury, myocardial infarction and stroke.
• Discovered that SR-BI in endothelial caveolae/rafts mediates both the vasculoprotective actions of HDL and the subendothelial delivery of LDL that drives atherogenesis.
• Discovered that endothelial apoER2 (LRP8) is the linchpin by which antiphospholipid antibodies invoke thrombosis in the antiphospholipid syndrome.
• Identified 27HC as the first endogenous selective ER modulator, or SERM, and showed that 27HC antagonizes the beneficial vascular actions of estrogens.
• Discovered that in obesity IgG is hyposialylated, and that via endothelial FcγRIIB, hyposialylated IgG drives obesity-associated hypertension and insulin resistance.