Van Beusecum Research Lab

Assistant Professor
Division of Nephrology

The pathogenesis of hypertension is still poorly understood, but over the last decade it has become clear that inflammation plays a critical role in development of high blood pressure. Virtually all cells of both the innate and adaptive immune system contribute to the genesis of hypertension. We investigate the role of dendritic cells (DCs) in the development of essential hypertension. Specifically, we focus on the role of growth arrest specific-6 (GAS6), the ligand for the Axl receptor signaling pathway in blood pressure elevations. In the past year, we have discovered that hypertensive human subjects have increased circulating Axl+ Siglec-6+ DCs compared to normotensive human subjects. Moreover, we found that mice lacking Axl, Axl knockout mice, are protected from hypertension and its associated renal inflammation. We found that an activated endothelium secretes GAS6, which in turn activates monocytes and DCs to promote a pro-inflammatory phenotype. Lastly, we have recently found that deletion of Axl on somatic cells (vessels, epthelial cells, etc.) or on immunological cells prevents hypertension, suggesting that both the immune system and somatic cells play a role in the development of hypertension.

Although the exact mechanism by which the endothelium and innate immune cells interact, we hypothesize that mechanical forces (endothelial stretch or shear stress), activate the endothelium and promote the secretion of GAS6 to activate Axl on monocytes and DCs. We propose that targeted deletion of either GAS6 or Axl on endothelial cells or DCs would prevent hypertension and its associated renal inflammation.

As a basic scientist trained in cardiovascular and renal physiology, I am particularly interested in translational research that brings novel mechanisms and therapeutic targets from bench to bedside.

Publications

PubMed Collection

Google Scholar