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Katherine Wood, PhD
Katherine Wood, PhD
Research Assistant Professor
E1341A Thomas Starzl Biomedical Science Tower
200 Lothrop Street
Pittsburgh, PA 1 5261
katherine.wood@pitt.edu
Education
B.A. (Political Science), University of Southwestern Louisiana, 1991
Ph.D. (Molecular and Cellular Physiology), Louisiana State University Health Sciences Center, 2006 Postdoctoral Research Fellow (Pulmonary and Vascular Medicine 2006-2009, Vascular Biology and Hypertension 2009-2010), (Neuroendocrine Tumor Program) Louisiana State University Health Sciences Center, 2012-2014;
Research Details
Publications
Research Areas
Cardiovascular and Renal Pharmacology
Neuropharmacology
Pulmonary Pharmacology
Redox Pharmacology
Signal Transduction
Research Focus
Dr. Wood’s research centers on molecular and cellular mechanisms of dysfunctional redox-dependent homeostasis in vasculo-, neuro- and hemato-symptomatic disease states, such as anemia, ischemic stroke and sickle cell disease (SCD). High levels of oxidative stress that uncouples the nitric oxide-soluble guanylate cyclase-protein kinase G (NO-sGC-PKG) signaling pathway for vascular relaxation responses to altered blood flow are common to these disease states. Cytochrome b5 reductase 3 (CYB5R3), also known as methemoglobin reductase, is critical for maintaining the sensitivity and signaling integrity of the NO-cGMP-PKG pathway. CYB5R3 is important for recycling oxidized sGC heme iron (Fe
3+
) back to its NO-receptive Fe
2+
state, which has been shown both in vitro and in mouse models of NO resistance, pulmonary hypertension, brain infarct and anemia.
Molecular and Cellular Studies of CYB5R3-NO-sGC-PKG Signaling in Disease
It is noteworthy that some disease states occur with greater frequency and worse outcomes in persons of African ancestry: SCD, ischemic stroke, anemia. The reasons for this, however, remain largely unknown. There are more than 40 identified variants of
CYB5R3
and a variant of particular interest is CYB5R3 T117S because it occurs with high frequency (0.23 minor allele) in persons of African ancestry but is rare in other racial groups (<1%). The T117S variant has roughly 50% decreased reductase activity, rendering it a logical mediator of impaired NO-cGMP-PKG signaling in these disease states. A novel mouse model of T117S is being used to investigate the variant’s effects on ischemic stroke, as well as SCD vasculopathy and anemia. Parallel studies with CYB5R3 knockout or overexpression in specific cell types (smooth muscle cell, endothelial cell, platelet, and bone marrow) are also ongoing to understand the importance of CYB5R3 activity at a cell-specific level.
Translational Research
The goal of these studies is to uncover identifiers/determinants of disease processes that can be used at the clinical level to improve diagnoses and treatment options for high-risk patients. Opportunities for harnessing the potential of CYB5R3-targeted pharmaceuticals, such as sGC agonists (stimulators and activators), for improved clinical management of lung, blood and vascular diseases in high-risk patients are also being explored and exploited by Dr. Wood.
Journal Articles
Wood KC
, Gladwin MT and Straub AC. Sickle cell disease at the crossroads of pulmonary hypertension and diastolic heart failure. Heart 106(8):562-568, 2020.
Wood KC
, Durgin BG, Schmidt HM, Hahn SA, Baust JJ, Bachman T, Vitturi DA, Ghosh S, Ofori-Acquah SF, Mora AL, Gladwin MT and Straub AC. Smooth muscle cytochrome b5 reductase 3 deficiency accelerates pulmonary hypertension development in sickle cell mice. Blood Adv 3(23)4104-4116, 2019.
Potoka KP,
Wood KC
, Baust JJ, Bueno M, Hahn SA, Vanderpool RR, Bachman T, Mallampalli GM, Osei-Hwedieh DO, Schrott V, Sun B, Bullock GC, Becker-Pelster EM, Wittwer M, Stampfuss J, Mathar I, Stasch JP, Truebel H, Sandner P, Mora AL, Straub AC and Gladwin MT. Nitric oxide-independent soluble guanylate cyclase activation improves vascular function and cardiac remodeling in sickle cell disease. Am J Respir Cell Mol Biol 58(5):636-647, 2018.
Wood KC
, Cortese-Krott MM, Kovacic JC, Noguchi A, Liu VB, Wang X, Raghavachari N, Boehm M, Kato GJ, Kelm M and Gladwin MT. Circulating blood endothelial nitric oxide synthase contributes to the regulation of systemic blood pressure and nitrite homeostasis. Arterioscler Thromb Vasc Biol 33(8):1861-1871, 2013.
Wood KC
, Hebbel RP, Lefer DJ and Granger DN. Critical role of endothelial cell-derived nitric oxide synthase in sickle cell disease-induced microvascular dysfunction. Free Radic Biol Med 40(8):1443-1453, 2006.
Wood KC
, Hebbel RP and Granger DN. Endothelial cell NADPH oxidase mediates the cerebral microvascular dysfunction in sickle cell transgenic mice. FASEB J 19(8):989-991, 2005.