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Department of Medicine

Department of Medicine

  Division of Pulmonary, Allergy and Critical Care Medicine



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photo Mark T. Gladwin, MD

Jack D. Myers Professor and Chair

Department of Medicine

Director, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute

Email: gladwinmt@upmc.edu

Phone: 412-648-9636

Contact
Office: 1218 Scaife Hall
3550 Terrace Street
Pittsburgh, PA 15261
 
Phone: 412-648-9636
Fax: 412-648-2117
E-mail: gladwinmt@upmc.edu
Administrative Assistant:
Sara Pecora
Address: 1218 Scaife Hall
3550 Terrace Street
Pittsburgh, PA 15261
Email: pecorase@upmc.edu
Phone: 412-648-9636
Administrative Assistant:
Laura Pliske
Address: 1218 Scaife Hall
3550 Terrace Street
Pittsburgh, PA 15261
Email: pliskelj@upmc.edu
Phone: 412-648-9641
Education and Training
Education
BS and MD, University of Miami Honors Program, 1991
Training
Internship, Residency, Oregon Health Sciences University, 1994
Chief Resident, Oregon Health Sciences University, 1995
Critical Care Fellow, Warren G. Magnuson Clinical Center, NIH, 1996
Pulmonary-Critical Care Fellow, University of Washington, 1998
Research Interest
Since 1998, Dr. Gladwin's research activities have led to numerous scientific discoveries. These discoveries have resulted in more than 210 published peer-reviewed manuscripts.
These investigations form the backbone of Dr. Gladwin’s current work in the Department of Medicine:
1) The discovery that the nitrite anion is a circulating storage pool for NO bioactivity (Gladwin, et al. PNAS 2000) that regulates hypoxic vasodilation (Cosby Nature Medicine 2003) and the cellular resilience to low oxygen and ischemia (Duranski JCI 2005).
2) The discovery of a novel physiological function for hemoglobin as an electronically and allosterically-regulated nitrite reductase (Cosby, et al. Nature Medicine 2003; Huang et al. JCI 2005).
3) The characterization of a novel mechanism of disease, hemolysis-associated endothelial dysfunction (Reiter, et al. Nature Medicine 2002; Morris et al. JAMA 2005; Minneci et al. JCI 2005; Rother et al. JAMA 2005).
4) The mechanistic, clinical, and epidemiological description of a human disease syndrome, hemolysis-associated pulmonary hypertension (Gladwin, et al. NEJM 2004).
Clinical Interest
Dr. Gladwin's clinical specialty is in the diagnosis and treatment of patients with pulmonary hypertension and sickle cell disease. He is an expert in heart and lung complications of sickle cell disease, which occur with increasing frequency as patients are aging. He also attends regularly in the Medical Intensive Care Unit at Presbyterian Hospital, focused on the care of critically ill patients and their families.

Dr. Gladwin’s clinical research focuses on pulmonary hypertension and pulmonary complications of sickle cell disease. He currently serves as PI on a new multi-center clinical trial of Riociguat to treat patients with sickle cell disease and pulmonary hypertension, and has served as PI on the multi-center clinical trials Walk-PHASST (Pulmonary Hypertension and Sickle Sildenafil Therapy Trial) and DeNOVO (Delivery of NO for Vaso-Occlusive pain crisis in sickle cell disease). He has served as a principal or associate investigator on more than 50 human subjects protocols and has held 10 FDA INDs for the use of investigational therapeutic medications, including inhaled, intravenous and oral preparations of sodium nitrite, carbon monoxide, L-NMMA, acetylcholine, riociguat and sildenafil.
Publications
For my complete bibliography, Click Here.
Selected Publications:
Huang Z, Shiva S, Kim-Shapiro DB, Patel RP, Ringwood LA, Irby CE, Huang KT, Ho C, Schechter AN, Hogg N, Gladwin MT. Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control. Journal of Clinical Investigation. 2005; 115(8): 2099-2107.
Gladwin MT, Sachdev V, Jison ML, Plehn JF, Minter K, Brown B, Coles WA, Nichols JS, Ernst I, Hunter LA, Blackwelder W, Schechter AN,, Rodgers GP, Castro O, Ognibene FP. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. New England Journal of Medicine. 2004; 350(9): 886-895.
Cosby K, Partovi KS, Crawford JH, Patel RP, Reiter CD, Martyr S, Yang BK, Waclawiw MA, Zalos G, Xu X, Huang KT, Shields H, Kim-Shapiro DB, Schechter AN, Cannon RO III, Gladwin MT. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nature Medicine. 2003; 9(12): 1498-1505.
Reiter CD, Wang X, Tanus-Santos JE, Hogg N, Cannon RO III, Schechter AN, Gladwin MT. Cell-free hemoglobin limits nitric oxide bioavailability in sickle cell-disease. Nature Medicine. 2002; 8(12): 1383-1389.
Gladwin MT. Cardiovascular Complications and Risk of Death in Sickle-Cell Disease. Lancet. 2016; 387(10037): 2565-74.
Lai YC, Tabima DM, Dube JJ, Hughan KS, Vanderpool RR, Goncharov DA, St Croix CM, Garcia-Ocana A, Goncharova EA, Tofovic SP, Mora AL, Gladwin MT. SIRT3-AMP-Activated Protein Kinase Activation by Nitrite and Metformin Improves Hyperglycemia and Normalizes Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction. Circulation. 2016; 133(8): 717-31.
Lundberg JO, Gladwin MT, Weitzberg E. Strategies to increase nitric oxide signalling in cardiovascular disease. Nature Reviews Drug Discovery. 2015; 14(9): 623-41.
Gladwin MT, O'Donnell CP. Training pulmonary researchers to span the bench-to-bedside "Valley of Death". American Journal of Respiratory and Critical Care Medicine. 2014; 190(9): 977-80.
Klings ES, Machado RF, Barst RJ, Morris CR, Mubarak KK, Gordeuk VR, Kato GJ, Ataga KI, Gibbs JS, Castro O, Rosenzweig EB, Sood N, Hsu L, Wilson KC, Telen MJ, Decastro LM, Krishnamurti L, Steinberg MH, Badesch DB, Gladwin MT. An official American Thoracic Society clinical practice guideline: diagnosis, risk stratification, and management of pulmonary hypertension of sickle cell disease. American Journal of Respiratory and Critical Care Medicine. 2014; 189(6): 727-40.
Donadee C, Raat NJ, Kanias T, Tejero J, Lee JS, Kelley EE, Zhao X, Liu C, Reynolds H, Azarov I, Frizzell S, Meyer EM, Donnenberg AD, Qu L, Triulzi D, Kim-Shapiro DB, Gladwin MT. Nitric oxide scavenging by red blood cell microparticles and cell-free hemoglobin as a mechanism for the red cell storage lesion. Circulation. 2011; 124(4): 465-76.
Sponsored Research/Activities
Title: Training in Translational Research and Entrepreneurship in Pulmonary Vascular Biology
Role: Principal Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: T32 HL110849
Start Year: 2017
End Year: 2022
Title: Vascular Subphenotypes of Lung Disease
Role: Principal Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: P01 HL103455
Start Year: 2016
End Year: 2021
Title: Antidote for Inhaled CO Poisoning Based on Mutationally Engineered Neuroglobin
Role: Principal Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL125886
Start Year: 2014
End Year: 2018
Title: Influence of Treprostenil on RV Function and Metabolism
Role: Principal Investigator
Funding Agency: United Therapeutics Corp.
Start Year: 2014
End Year: 2016
Title: Use of SGC Activators to Bypass NO Scavenging in SCD
Role: Principal Investigator
Funding Agency: Bayer Corporation
Start Year: 2014
End Year: 2016
Title: The Use of sCG Activators to Bypass Nitric Oxide Scavenging by Hemolysis in Sickle Cell Disease
Role: Principal Investigator
Funding Agency: Bayer Corporation
Start Year: 2013
End Year: 2014
Title: Hemostasis and Vascular Biology Research Institute - Gladwin
Role: Principal Investigator
Funding Agency: Hemophilia Center of Western PA
Start Year: 2012
End Year: 2018
Title: Translational Pulmonary Vascular Biology
Role: Principal Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: T32 HL110849
Start Year: 2012
End Year: 2017
Title: Vascular Subphenotypes of Lung Disease - Project 3
Role: Principal Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: P01 HL103455
Start Year: 2011
End Year: 2016
Title: The Effects of Selective Adenoside A2B Receptor Antagonist GC-6201 on Adenosine Induced Red Blood Cells Sickling in SCD Patients
Role: Principal Investigator
Funding Agency: Gilead Sciences, Inc
Start Year: 2011
End Year: 2013
Title: Hemostasis and Vascular Biology Research Institute - Administrative Core
Role: Principal Investigator
Funding Agency: Institute for Transfusion Medicine
Start Year: 2008
End Year: 2028
Title: Storage Lesion in Banked Blood Due to Disruption of Nitric Oxide Hemostasis
Role: Co-Principal Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL098032
Start Year: 2014
End Year: 2015
Title: Myoglobin as a Nitrate Reductase that Regulates Hypoxic Cardiac NO Signaling
Role: Co-Principal Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL096973
Start Year: 2010
End Year: 2014
Title: Storage Lesion in Banked Blood Due to Disruption of Nitric Oxide Hemostasis
Role: Co-Principal Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL098032
Start Year: 2009
End Year: 2014
Title: Dual Role of HMGB1 in Pathogenic Platelet Biology in Pulmonary Hypertension
Role: Co-Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL130268
Start Year: 2017
End Year: 2022
Title: Nitrite Benefits to Mediate Fatigability in Older HFpEF Patients
Role: Co-Investigator
Funding Agency: National Institute of Aging
Grant Number: R01 AG051637
Start Year: 2016
End Year: 2017
Title: Network Management Core (NEMO) for the Pulmonary Trials Cooperative (PTC)
Role: Co-Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: U01 HL128954
Start Year: 2015
End Year: 2020
Title: Role of Erythroid DAMP Molecules in the Pathogenesis of Vascular Injury in Sepsis
Role: Co-Investigator
Funding Agency: National Institute of General Medical Science
Grant Number: R01 GM113816
Start Year: 2015
End Year: 2019
Title: Reactive Oxygen Species in Vascular Disease
Role: Co-Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL079207
Start Year: 2015
End Year: 2019
Title: Genetic Basis of Differential Blood Donor RBC Storage Capacity/Polymorphisms that Improve Hemoglobin and/or Storage Iron in High Intensity Blood Donors
Role: Co-Investigator
Funding Agency: Institute for Transfusion Medicine
Start Year: 2015
End Year: 2016
Title: A Dose Escalation Study to Evaluate the Effect of Inhaled Nitrite on Cardiopulmonary Hemodynamics in Subjects with Pulmonary Hypertension
Role: Co-Investigator
Funding Agency: Aires Pharmaceuticals, Inc.
Grant Number: DRUG
Start Year: 2014
End Year: 2016
Title: Genetic Basis of Differential Blood Donor RBC Storage Capacity/Polymorphisms that Improve Hemoglobin and/or Storage Iron in High Density Blood Donors Study - Phase 1
Role: Co-Investigator
Funding Agency: Blood Systems, Inc./National Institute of Health
Start Year: 2013
End Year: 2017
Title: RV/PA Recoupling by Bone Marrow Derived Mesenchymal Stem Cells
Role: Co-Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL114795
Start Year: 2012
End Year: 2017
Title: Effects of Nitric Oxide in Sickle Cell Blood
Role: Co-Investigator
Funding Agency: Wake Forest University/National Heart, Lung, & Blood Institute
Grant Number: R37 HL058091
Start Year: 2012
End Year: 2017
Title: Biodegradable Synthetic Vascular Graft
Role: Co-Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL089658
Start Year: 2012
End Year: 2017
Title: Small Molecule, Gas Based Therapies to Prevent Organ Injury from Trauma/Hemorrhage
Role: Co-Investigator
Funding Agency: Department of Defense
Start Year: 2010
End Year: 2014
Title: Role of Nitrate and Hemoglobin in Vascular NO Homeostasis in the Fetus and Adult
Role: Co-Investigator
Funding Agency: Loma Linda Univeristy/National Heart, Lung, & Blood Institute
Grant Number: R01 HL095973
Start Year: 2009
End Year: 2013
Notable Achievements
Achievement Medal, US Public Health Service, NIH, 1999
Clinical Center Director’s Award, Science Category, 2002
NIH Director’s Award for Mentoring, 2006
American Society of Clinical Investigations (ASCI), 2006-present
Recognition Award for Scientific Accomplishments from the American Thoracic Society, 2013
Recognized as Distinguished Professor at the University of Pittsburgh, 2014