Wallace H. Coulter Laboratory

Cardiovascular Dynamics and Biomolecular Transport Laboratory

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Back row: Zhong-Dong Shi, Limary M. Cancel, Danielle E. Berardi, Mishal Rahman, Giya Abraham
Front row: Veronica Lopez, Maria Nikmanesh, Dr. John M. Tarbell, Ronny Amaya, Henry Qazi.

Cardiovascular Dynamics and Biomolecular Transport Laboratory

The Wallace Coulter Laboratory for Cardiovascular Dynamics and Biomolecular Transport is directed by John Tarbell, The CUNY and Wallace Coulter Distinguished Professor of Biomedical Engineering, and is housed in 3500 ft2 of newly renovated space in Steinman Hall.The Laboratory contains extensive facilities for cell culture, molecular biology, biomaterials and microscopy that support a broad range of biotransport and biomechanics experiments. The Laboratory is also active in computer simulations of biotransport processes and has been involved in large scale simulations through the National Supercomputer Center.Currently six Ph.D. students, one post doctoral fellow and several undergraduate assistants are conducting research in the Laboratory, while several collaborations with U.S. scientists and foreign scientists broaden the scope of the Laboratory’s studies.

The role of fluid mechanics and transport processes in the physiological and pathophysiological functions of the cardiovascular system are of primary interest to the Coulter Lab group. One of our major efforts is to understand the influence of fluid dynamics in the initiation and progression of atherosclerosis, a degenerative disease of the large human arteries that leads to heart attacks and strokes. We are investigating the fluid mechanics of arteries and the response of arterial cells (endothelial and smooth muscle cells) to fluid mechanical forces using cell culture models in vitro, computer simulations, and animal models in vivo in collaboration with other scientists. We were the first group to compute the fluid flow shear stresses on smooth muscle cells (SMCs) induced by transmural flow and have subsequently exposed cultured SMCs to similar stress environments in defined flow fields to determine their biomolecular responses.We have recently demonstrated that transvascular flow driven by vascular pressure plays a major role in the myogenic response by which arterioles control blood flow distribution in response to changes in pressure.We have also demonstrated that transvascular flow inhibits smooth muscle migration and is therefore an important factor in modulating vascular remodeling in intimal hyperplasia.We have shown that unique patterns of vessel stretch and fluid shear stress driven by blood flow may predispose coronary, carotid and other vessels at risk for atherosclerosis, to an atherogenic gene profile.Most recently we have observed that the surface glycoprotein layer on endothelial and smooth muscle cells (the glycocalyx layer) is a mechanosensor that recognizes the state of fluid flow (shear stress) over the cell surface and transmits this information into a cellular biochemical signaling cascade.

In complementary research, we have pioneered in vitro studies of convection and diffusion of macromolecules across monolayers of endothelial cells that form the blood contacting surface of all blood vessels. We were the first group to clearly demonstrate that the transport properties of the endothelial layer are very sensitive to their fluid mechanical environment and respond to changes in fluid shear stress. Studies of the biomolecular mechanisms underlying these responses, including the disassembly of inter-endothelial tight molecular junctions are in progress.The transport properties of the endothelium also respond to changes in transvascular pressure, and our group has uncovered important mechanisms mediating these responses.A very active area for the group has been the study of low density lipoprotein (LDL) transport across the endothelium.Most current therapies directed at controlling LDL accumulation in the vascular wall to reduce the risk of heart attacks and strokes have focused on lowering LDL levels in blood (the use of statins, for example).We are pursuing a novel strategy of manipulating the permeability of the endothelium to LDL.This requires a thorough understanding of the mechanisms by which LDL is transported across the endothelial layer.

 

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