BME Seminar Series: Dr. Kenneth Barbee, Drexel University

Dr. Kenneth Barbee, Drexel University, School of Biomedical Engineering, Science and Health Systems

“Transport-dependent Signaling Processes in Flow-induced Endothelial Nitric Oxide Production.”

Abstract

Nitric oxide (NO) is mediates a wide range of behaviors critical to normal vascular function. In addition to its primary role as a powerful vasodilator, NO inhibits platelet aggregation, adhesion of leukocytes to endothelium, and prevents vascular smooth muscle cell proliferation. Impairment in NO availability is a characteristic of endothelial dysfunction in atherosclerosis and hypertension. Shear stress-induced NO release is a well-established phenomenon, yet the cellular mechanisms of this response are not completely understood.  Endothelial nitric oxide synthase (eNOS) is not uniformly distributed throughout the cell but rather is spatially compartmentalized in plasma membrane domains known as caveolae where it is co-localized with signaling molecules involved in its regulation. We present evidence for the critical importance of the caveolar localization of eNOS and show how intracellular and extracellular transport phenomena contribute to the control of NO production and its bioavailability. Shear stress-induced release of ATP stimulates NO production in an autocrine fashion that depends on extracellular diffusive and convective transport.  The intracellular signaling leading to NO production also depends on spatial distribution of sources and targets of diffusible signaling intermediates.  Finally, we show that cholesterol enrichment of the plasma membrane interferes with a key component in the pathway.

 

Kenneth Barbee, PhD, is a Professor and Interim Director of the School of Biomedical Engineering, Science, and Health Systems at Drexel University. He received his bachelor’s degree in engineering science and mechanics from the University of Tennessee in 1986 and his PhD from the University of Pennsylvania in 1991. He completed a post-doctoral fellowship in the department of pathology at the University of Chicago. He joined the faculty at Drexel in 1998, shortly after the founding of the School of Biomedical Engineering, Science & Health Systems. In 2014, he became interim Director of the School and PI of the Coulter-Drexel Translational Research Partnership Program. He also directs an NIH-supported undergraduate training program in Biomedical Engineering Design that features a clinical immersion experience leading to the development of a senior design project. He is a Fellow of the American Institute for Medical and Biological Engineering. Dr. Barbee is recognized for his contributions to a wide variety of fields related to mechanics and transport at the cellular level. He was among the first investigators to use Atomic Force Microscopy to image living cells. He used the surface topography data of vascular endothelial cells to determine the subcellular shear stress distribution due to blood flow. Current studies in cardiovascular mechanotransduction focus on the signaling events related to nitric oxide (NO) production, combining novel experimental approaches and mathematical modeling of mass transport phenomena at the cellular level.