Jeannette Vasquez-Vivar, PhD

Jeannette Vasquez Vivar, PhD

Professor of Biophysics

Associate Director, Redox Biology Program

414-955-8095
jvvivar@mcw.edu


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.

Research Interests

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.

 Selected Publications
  • Yu L, Vásquez-Vivar J, Jiang R, Luo K, Derrick M, Tan S. Developmental susceptibility of neurons to transient tetrahydrobiopterin insufficiency and antenatal hypoxia-ischemia in fetal rabbits. Free Radic Biol Med. 2014 Feb;67:426-36. doi: 10.1016/j.freeradbiomed.2013.11.026. Epub 2013 Dec 4.  PMID:24316196  [PubMed - in process]

  • Whitsett J, Rangel Filho A, Sethumadhavan S, Celinska J, Widlansky M, Vasquez-Vivar J.  Human endothelial dihydrofolate reductase low activity limits vascular tetrahydrobiopterin recycling. Free Radic Biol Med. 2013 Oct;63:143-50. doi: 10.1016/j.freeradbiomed.2013.04.035. Epub 2013 May 23. PMID:23707606 [PubMed - indexed for MEDLINE]

  • Sethumadhavan S, Vasquez-Vivar J, Migrino RQ, Harmann L, Jacob HJ, Lazar J.  Mitochondrial DNA variant for complex I reveals a role in diabetic cardiac remodeling. J Biol Chem. 2012;287(26):22174-82.

  • Drobyshevsky A, Luo K, Derrick M, Yu L, Du H, Prasad PV, Vasquez-Vivar J, Batinic-Haberle I, Tan S.  Motor deficits are triggered by reperfusion-reoxygenation injury as diagnosed by MRI and by a mechanism involving oxidants. J Neurosci. 2012;32(16):5500-9.

  • Wang J, Alexanian A, Ying R, Kizhakekuttu TJ, Dharmashankar K, Vasquez-Vivar J, Gutterman DD, Widlansky ME.  Acute exposure to low glucose rapidly induces endothelial dysfunction and mitochondrial oxidative stress: role for AMP kinase. Arterioscler Thromb Vasc Biol. 2012 Mar;32(3):712-20. doi: 10.1161/ATVBAHA.111.227389.

  • Mao M, Sudhahar V, Ansenberger-Fricano K, Fernandes DC, Tanaka LY, Fukai T, Laurindo FR, Mason RP, Vasquez-Vivar J, Minshall RD, Stadler K, Bonini MG.  Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway. Free Radic Biol Med. 2012;52(2):427-35.

  • Ge ZD, Ionova IA, Vladic N, Pravdic D, Hirata N, Vásquez-Vivar J, Pratt PF Jr, Warltier DC, Pieper GM, Kersten JR.  Cardiac-specific overexpression of GTP cyclohydrolase 1 restores ischaemic preconditioning during hyperglycaemia.  Cardiovasc Res. 2011 Jul 15;91(2):340-9. Epub 2011 Mar 21.

  • Yu L, Derrick M, Ji H, Silverman RB, Whitsett J, Vásquez-Vivar J, Tan S.  Neuronal Nitric Oxide Synthase Inhibition Prevents Cerebral Palsy following Hypoxia-Ischemia in Fetal Rabbits: Comparison between JI-8 and 7-Nitroindazole.  Dev Neurosci. 2011 Jun 10. [Epub ahead of print]

  • Ionova IA, Vásquez-Vivar J, Cooley BC, Khanna AK, Whitsett J, Herrnreiter A, Migrino RQ, Ge ZD, Regner KR, Channon KM, Alp NJ, Pieper GM.  Cardiac myocyte-specific overexpression of human GTP cyclohydrolase I protects against acute cardiac allograft rejection. Am J Physiol Heart Circ Physiol. 2010 Jul;299(1):H88-96. Epub 2010 Apr 23.

  • Du J, Wei N, Xu H, Ge Y, VÁSQUEZ-VIVAR J, Guan T, Oldham KT, Pritchard KA Jr, Shi Y. Identification and functional characterization of phosphorylation sites on GTP cyclohydrolase I. Arterioscler. Thromb. Vasc. Biol. 29:2161-2168 (2009).

  • Hein TW, Singh U, VÁSQUEZ-VIVAR J, Devaraj S, Kuo L, Jialal I. Human C-reactive protein induces endothelial dysfunction and uncoupling of eNOS in vivo. Atherosclerosis 206:61-68 (2009).

  • Ji H, Tan S, Igarashi J, Li H, Derrick M, Martásek P, Roman LJ, VÁSQUEZ-VIVAR J, Poulos TL, Silverman RB. Selective neuronal nitric oxide synthase inhibitors and the prevention of cerebral palsy. Ann. Neurol. 65:209-217 (2009).

  • Pieper GM, Ionova IA, Cooley BC, Migrino RQ, Khanna AK, Whitsett JW, VÁSQUEZ-VIVAR J. Sepiapterin decreases acute rejection and apoptosis in cardiac transplants independent of changes in nitric oxide and iNOS dimerization. J. Pharmacol. Exp. Ther. 329:890-899 (2009).

  • Rabbani ZN, Spasojevic I, Zhang X, Moeller BJ, Haberle S, VÁSQUEZ-VIVAR J, Dewhirst MW, Vujaskovic Z, Batinic-Haberle I. Antiangiogenic action of redox-modulating Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, MnTE-2-PyP(5+), via suppression of oxidative stress in a mouse model of breast tumor. Free Radic. Biol. Med. 47:992-1004 (2009).

  • VÁSQUEZ-VIVAR J. Tetrahydrobiopterin, superoxide, and vascular dysfunction. Free Radic. Biol. Med. 47:1108-1119 (2009).

  • VÁSQUEZ-VIVAR J, Whitsett J, Derrick M, Ji X, Yu L, Tan S.  Tetrahydrobiopterin in the prevention of hypertonia in hypoxic fetal brain. Ann. Neurol. 66:323-331 (2009).

  • Ionova IA, VÁSQUEZ-VIVAR J, Whitsett J, Herrnreiter A, Medhora M, Cooley BC, Pieper GM. Deficient BH4 production via de novo and salvage pathways regulates NO responses to cytokines in adult cardiac myocytes. Am. J. Physiol. Heart Circ. Physiol. 295:H2178-H2187 (2008).

  • VÁSQUEZ-VIVAR J, Whitsett J, Ionova I, Konorev E, Zielonka J, Kalyanaraman B, Shi Y, Pieper GM. Cytokines and lipopolysaccharides induce inducible nitric oxide synthase but not enzyme activity in adult rat cardiomyocytes. Free Radic. Biol. Med. 45:994-1001 (2008).

  • Zielonka J, Srinivasan S, Hardy M, Ouari O, Lopez M, VÁSQUEZ-VIVAR J, Avadhani NG, Kalyanaraman B. Cytochrome c-mediated oxidation of hydroethidine and mito-hydroethidine in mitochondria: Identification of homo- and heterodimers. Free Radic. Biol. Med. 44:835-846 (2008).

  • Zielonka J, VÁSQUEZ-VIVAR J, Kalyanaraman B. Detection of 2-hydroxyethidium in cellular systems: A unique marker product of superoxide and hydroethidine. Nat. Protoc. 3:8-21 (2008).

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