Jeannette Vasquez-Vivar, PhD
Professor of Biophysics
Associate Director, Redox Biology Program
Department of Biophysics
Medical College of Wisconsin
8701 Watertown Plank Road
Milwaukee, WI 53226-0509
Education and Experience
I completed my bachelor's degree in Biochemistry at the Universidad de Concepción Chile, and my PhD degree in Biochemistry from the Universidade de São Paulo, Brazil. As a postdoctoral fellow, I investigated kinetics and mechanisms of free radical formation from reactions involving peroxynitrite and biomolecules, and later I discovered the role of tetrahydrobiopterin in the regulation of superoxide release from nitric oxide synthase. In 1998, I became a faculty member in the Department of Pathology at the Medical College of Wisconsin, studying the endothelial nitric oxide synthase uncoupling in endothelial dysfunction. In 2001, I joined the faculty of the Department of Biophysics at the Medical College of Wisconsin, where I continue my work on redox mechanisms of cardiovascular and fetal brain dysfunction. My research is supported by the National Institutes of Health.
The general interest of my lab is to investigate cell-specific redox mechanisms disrupting normal cellular homeostasis. We have focused on three different systems: fetal brain, heart and endothelial cells.
The project dealing with fetal brain is supported by our discovery that developmentally low tetrahydrobiopterin (BH4) cofactor in the fetal brain increases hypoxia-ischemia injury in specific brain regions and worsens motor disabilities in newborns. Our working hypothesis is that development of motor deficits can be explained by a two hit model where transient low tetrahydrobiopterin represents an important vulnerability state of immature fetal brain neurons.
The heart project investigates the influence of mitochondrial DNA variants in cardiac remodeling. We have shown that hearts from conplastic rat strains (i.e., animals with identical nuclear but different mitochondrial genome) expressing mtDNA variant (mtFHH) leading to low complex I activity and bioenergetic impairments, undergo cardiac remodeling. We hypothesize that the decreased OXPHOS activity translates into NAD+-regulated redox signaling from mitochondria to nuclear genome capable of promoting cardiac adaptive growth responses.
The endothelial project examines the relationship between endothelial dysfunction and eNOS uncoupling in an animal model of atherosclerosis. While eNOS dysfunction is believed to be an important element promoting vascular dysfunction, it is yet unclear whether ‘eNOS-uncoupling’ controls a state of critical oxidant stress to promote disease. In this project we are examining whether eNOS uncoupling is necessary to reach a state of critical oxidative stress causing significant changes in the vascular wall and testing its reversibility by BH4 therapies.