Georgia Tech, Emory professor to give vascular biology talk Monday

Dr. Larry V. McIntire, Wallace H. Coulter Professor and chair of the Coulter Department of Biomedical Engineering at the Georgia Institute of Technology and Emory University, will give a talk Monday (Feb. 15) at 4:10 p.m. in Room 104 of the Jack E. Brown Engineering Building on campus.The seminar, "Role of Mechanical Forces in Vascular Biology: From Cells to Molecules," is part of the Texas A&M Department of Biomedical Engineering's seminar series.Abstract Understanding the molecular basis of the modulation of vascular phenotype by mechanical forces (stresses induced by blood flow and vessel wall strain) is an area of great significance in vascular biology. It is hypothesized that certain flow environments (arterial flow, non-reversing) lead to anti-atherogenic endothelium, while low mean wall shear stress reversing flows promote a pro-atherogenic endothelium. We examined in a flow chamber human endothelial cells exposed to high (15 dynes/cm2) and low (1 dyne/cm2) steady shear stress and a reversing waveform characteristic of the carotid sinus (time average 1 dyne/cm2) using whole human genome microarray studies. We demonstrated unique sets of genes controlled by both low average shear stress and by reversing flow, with more genes controlled by low average stress. Functional studies confirmed that reversing flow increases cell proliferation and monocyte adhesion.Detailed studies of two cytochrome P450 genes that are maximally up-regulated by steady arterial levels of shear stress (CYP1A1 and CYP 1B1) demonstrated strong attenuation by reversing flows. Furthermore, CYP1A1 protein and AhR nuclear localization correlate with flow patterns in the mouse aortic arch in vivo. Finally, as a result of changes observed in zinc-binding and zinc transporter proteins, changes in free zinc were measured under different shear stresses. High steady shear stress exposure dramatically increases the levels of free zinc in endothelial cells.In addition, we have utilized AFM force clamp experiments to characterize the effect of force on G-actin/G- actin and G-actin/F-actin bond life lifetimes. We found biphasic catch bond/slip bond behavior with increasing force that could be switched to pure slip bonds by formin regulated by a RhoA-mediated autoinhibition. This gives the cell a mechanism of regulating actin polymerization kinetics by force coupled to biochemical signaling.Biography Dr. Larry V. McIntire joined the Georgia Institute of Technology and the Emory University School of Medicine in 2003 as the Wallace H. Coulter Professor and chair of the Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. McIntire received his B.Ch.E. and M.S. degrees from Cornell University in 1966 and his Ph.D. from Princeton University in 1970 - all in chemical engineering. He joined Rice University in January 1970 as an assistant professor. McIntire served as chair of the Department of Chemical Engineering from 1982 to 1989, the E.D. Butcher Professor at Rice from 1982 to 2003, the founding chair of the Bioengineering Department there from 1997 to 2003 and the chair of the Institute of Biosciences and Bioengineering from 1991 to 2003. He is the author of more than 400 publications and papers in the areas of bioengineering applications in vascular biology, thrombosis, atherosclerosis, and inflammation.McIntire is also a Founding Fellow and past president of the American Institute of Medical and Biological Engineering. He is past president and Fellow of the Biomedical Engineering Society, past president of the North American Society of Biorheology, and a Fellow of the American Heart Association. McIntire was the 1992 recipient of the American Institute of Chemical Engineering Food, Pharmaceutical, and Bioengineering Division Award, chair of that division in 1998, elected a Fellow of that institute in 1994, the 1992 ALZA Distinguished Lecturer for the Biomedical Engineering Society, Sigma Xi National lecturer for 1993‐95 and in 1998, he was elected a Fellow of the American Association for the Advancement of Science. In 2001, McIntire was elected to the National Academy of Engineering and was appointed editor‐in‐chief of the Annals of Biomedical Engineering (the journal of the Biomedical Engineering Society), effective January 2002 through December 2009. Additionally, McIntire is the 2003 recipient of the Biomedical Engineering Society Distinguished Service Award and Presidential Award and the 2009 Distinguished Service Award.Submitted by Nicole A. Priolo,