Mark T. Gladwin

ORCID: 0000-0001-7267-9006
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About
Contact & Profiles
Research Areas
  • Hemoglobinopathies and Related Disorders
  • Nitric Oxide and Endothelin Effects
  • Hemoglobin structure and function
  • Iron Metabolism and Disorders
  • Pulmonary Hypertension Research and Treatments
  • Erythrocyte Function and Pathophysiology
  • Neuroscience of respiration and sleep
  • Heme Oxygenase-1 and Carbon Monoxide
  • Blood groups and transfusion
  • Neonatal Health and Biochemistry
  • Myeloproliferative Neoplasms: Diagnosis and Treatment
  • Cardiovascular Function and Risk Factors
  • Eicosanoids and Hypertension Pharmacology
  • Cardiac Ischemia and Reperfusion
  • Folate and B Vitamins Research
  • Epigenetics and DNA Methylation
  • Renin-Angiotensin System Studies
  • Transplantation: Methods and Outcomes
  • Pregnancy and preeclampsia studies
  • Genetic Associations and Epidemiology
  • High Altitude and Hypoxia
  • Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Bone and Joint Diseases
  • Electron Spin Resonance Studies
  • Heart Failure Treatment and Management

University of Pittsburgh
2016-2025

University of Maryland, Baltimore
2022-2025

National Heart Lung and Blood Institute
2005-2024

University of Maryland, College Park
2024

University of Iowa
2024

Bayer (United States)
2024

Actelion (Switzerland)
2024

University of Baltimore
2023-2024

Acceleron Pharma (United States)
2024

Novartis (Switzerland)
2024

Daniel Taliun Daniel Harris Michael D. Kessler Jedidiah Carlson Zachary A. Szpiech and 95 more Raúl Torres Sarah A. Gagliano Taliun André Corvelo Stephanie M. Gogarten Hyun Min Kang Achilleas Pitsillides Jonathon LeFaive Seung‐been Lee Xiaowen Tian Brian L. Browning Sayantan Das Anne‐Katrin Emde Wayne E. Clarke Douglas P. Loesch Amol C. Shetty Thomas W. Blackwell Albert V. Smith Quenna Wong Xiaoming Liu Matthew P. Conomos Dean Bobo François Aguet Christine M. Albert Álvaro Alonso Kristin Ardlie Dan E. Arking Stella Aslibekyan Paul L. Auer John Barnard R. Graham Barr Lucas Barwick Lewis C. Becker Rebecca Beer Emelia J. Benjamin Lawrence F. Bielak John Blangero Michael Boehnke Donald W. Bowden Jennifer A. Brody Esteban G. Burchard Brian E. Cade James F. Casella Brandon Chalazan Daniel I. Chasman Yii‐Der Ida Chen Michael H. Cho Seung Hoan Choi Mina K. Chung Clary B. Clish Adolfo Correa Joanne E. Curran Brian Custer Dawood Darbar Michelle Daya Mariza de Andrade Dawn L. DeMeo Susan K. Dutcher Patrick T. Ellinor Leslie Emery Celeste Eng Diane Fatkin Tasha E. Fingerlin Lukas Forer Myriam Fornage Nora Franceschini Christian Fuchsberger Stephanie M. Fullerton Søren Germer Mark T. Gladwin Daniel J. Gottlieb Xiuqing Guo Michael E. Hall Jiang He Nancy L. Heard‐Costa Susan R. Heckbert Marguerite R. Irvin Jill M. Johnsen Andrew D. Johnson Robert C. Kaplan Sharon L. R. Kardia Tanika N. Kelly Shannon Kelly Eimear E. Kenny Douglas P. Kiel Robert Klemmer Barbara A. Konkle Charles Kooperberg Anna Köttgen Leslie A. Lange Jessica Lasky‐Su Daniel Levy Xihong Lin Keng‐Han Lin Chunyu Liu Ruth J. F. Loos

Abstract The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood sleep disorders, with ultimate goal improving diagnosis, treatment prevention these diseases. initial phases focused on whole-genome sequencing individuals rich phenotypic data diverse backgrounds. Here we describe TOPMed goals design as well available resources early insights obtained from sequence data. include a variant browser, genotype...

10.1038/s41586-021-03205-y article EN cc-by Nature 2021-02-10

The prevalence of pulmonary hypertension in adults with sickle cell disease, the mechanism its development, and prospective prognostic significance are unknown.We performed Doppler echocardiographic assessments pulmonary-artery systolic pressure 195 consecutive patients (82 men 113 women; mean [+/-SD] age, 36+/-12 years). Pulmonary was prospectively defined as a tricuspid regurgitant jet velocity at least 2.5 m per second. Patients were followed for 18 months, data censored time death or...

10.1056/nejmoa035477 article EN New England Journal of Medicine 2004-02-25

Sickle cell disease is characterized by a state of nitric oxide resistance and limited bioavailability l-arginine, the substrate for synthesis. We hypothesized that increased arginase activity dysregulated arginine metabolism contribute to endothelial dysfunction, pulmonary hypertension, patient outcomes.To explore role in sickle pathogenesis, mortality.Plasma amino acid levels, plasma erythrocyte activities, hypertension status as measured Doppler echocardiogram were prospectively obtained...

10.1001/jama.294.1.81 article EN JAMA 2005-07-05

Nitrite represents a circulating and tissue storage form of NO whose bioactivation is mediated by the enzymatic action xanthine oxidoreductase, nonenzymatic disproportionation, reduction deoxyhemoglobin, myoglobin, heme proteins. Because rate generation from nitrite linearly dependent on reductions in oxygen pH levels, we hypothesized that would be reduced to ischemic exert NO-dependent protective effects. Solutions sodium were administered setting hepatic cardiac ischemia-reperfusion (I/R)...

10.1172/jci22493 article EN Journal of Clinical Investigation 2005-04-14

Previous studies have revealed a novel interaction between deoxyhemoglobin and nitrite to generate nitric oxide (NO) in blood. It has been proposed that acts as an endocrine reservoir of NO contributes hypoxic vasodilation signaling. Here, we characterize the reductase activity deoxymyoglobin, which reduces approximately 36 times faster than because its lower heme redox potential. We hypothesize physiologically this reaction releases proximity mitochondria regulates respiration through...

10.1161/01.res.0000260171.52224.6b article EN Circulation Research 2007-02-10

Background— Intravascular red cell hemolysis impairs nitric oxide (NO)–redox homeostasis, producing endothelial dysfunction, platelet activation, and vasculopathy. Red blood storage under standard conditions results in reduced integrity of the erythrocyte membrane, with formation exocytic microvesicles or microparticles hemolysis, which we hypothesized could impair vascular function contribute to putative lesion banked blood. Methods Results— We now find that human cells banking accumulation...

10.1161/circulationaha.110.008698 article EN Circulation 2011-07-12

Nitrite (NO2−) is an intrinsic signaling molecule that reduced to NO during ischemia and limits apoptosis cytotoxicity at reperfusion in the mammalian heart, liver, brain. Although mechanism of nitrite-mediated cytoprotection unknown, a mediator ischemic preconditioning cell-survival program. Analogous temporally distinct acute delayed cytoprotective phenotypes, we report both (24 h before ischemia) exposure physiological concentrations nitrite, given systemically or orally, potently cardiac...

10.1084/jem.20070198 article EN The Journal of Experimental Medicine 2007-08-06

To determine the relative contributions of endothelial-derived nitric oxide (NO) vs. intravascular nitrogen species in regulation human blood flow, we simultaneously measured forearm flow and arterial venous levels plasma nitrite, LMW-SNOs HMW-SNOs, red cell S-nitrosohemoglobin (SNO-Hb). Measurements were made at rest during regional inhibition NO synthesis, followed by exercise. Surprisingly, found significant circulating arterial-venous nitrite gradients, providing a novel delivery source...

10.1073/pnas.97.21.11482 article EN Proceedings of the National Academy of Sciences 2000-10-10
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