CBE Seminar - Daniel Kim-Shapiro

Professor and Associate Chair, Department of Physics, Wake Forest University

All dates for this event occur in the past.

130 Koffolt Laboratories, CBEC
130 Koffolt Laboratories, CBEC
151 W. Woodruff Ave
Columbus, OH 43210
United States

Nitric Oxide Bioavailability in Health, Disease and Therapeutics

 

Daniel B. Kim-Shapiro

Professor and Associate Chair
Department of Physics

Wake Forest University

Abstract

Nitric oxide (NO) is a key player in modulating vascular tone, angiogenesis, vascular permeability, platelet aggregation and adhesion, and leukocyte adhesion.  The maintenance of sufficient NO bioavailability in the presence of vast quantities of scavenging molecules such as hemoglobin and myoglobin is accomplished largely by compartmentalization, for example of hemoglobin in red cells.  Disruption of NO bioavailability due to hemolysis or other factors contributes to pathology in a variety of diseases and conditions including sickle cell disease, arteriosclerosis, cancer, diabetes, and transfusion of older stored blood.  We present studies elucidating basic physiological mechanisms that preserve NO bioavailability, how these are disturbed in various diseases, and how these can be preserved through therapeutics.  We have found that reduced NO scavenging by hemoglobin in normal physiology is mainly due to rate-limitations for NO to diffuse to the red cell but that red cell membrane permeability also plays a role and this is modulated by oxygen tension.  When hemolysis occurs, as little as one micromolar intravascular hemoglobin can drastically reduce NO bioavailability even in the presence of ten millimolar red cell encapsulated hemoglobin that is usually present.  NO bioavailability may be restored using nitrite therapy.  Contrary to the previously held belief that nitrite is biologically inert in human physiology, we and others have found that nitrite is a vasodilator and may serve as a storage pool for nitric oxide that is activated under hypoxic conditions.  This activation involves a new nitrite reductase/anhydrase activity of hemoglobin or other proteins.  Current therapeutic interventions being explored include use of oral nitrate and some of these intervention will also be discussed, including our recent study on patients with Heart Failure and Preserved Ejection Fraction.

Supported by the NIH.

 

Bio
Dr. Daniel Kim-Shapiro is a Professor and the Associate Chair of Physics and holds the Harbert Family Distinguished Chair for Excellence in Teaching and Scholarship at Wake Forest University. He also is the director of the Wake Forest Translational Science Center (TSC); Fostering Independence in Aging.

Dr. Kim-Shapiro earned a BA in physics at Carelton College, a MS in Physics from Southern Illinois University, and received a PhD in biophysics from the University of California at Berkeley, in 1993. Dr. Kim-Shapiro joined the faculty of Wake Forest in 1996. He employs physical tools and theory to solve problems in biology, focusing generally on reactive oxygen species, heme proteins, and blood flow.  He is currently studying the effects of nitrite and nitric oxide in biological systems, especially as it relates to sickle cell and other blood or cardiovascular diseases.  As director of the TSC, he also has a growing interest in aging research. 

 

Disclosures: Daniel Kim-Shapiro is listed as a co-inventor on several patent applications related to use of nitrite in cardiovascular conditions and/or treatment of hemolysis ,and owns stock in and serves on the scientific advisory board for Beverage Operations LLC which has licensed Wake Forest University intellectual properties and thus has a financial interest in Beverage Operations LLC.  [This company produces and sells a beet juice product].

 

 

Category: Seminar