Mark T. Gladwin, MD

  • Jack D. Myers Professor and Chair, Department of Medicine
  • Director, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute
  • Co-Director, Heart and Vascular Institute, UPMC

Education & Training

  • Medical School - University of Miami
  • Residency - Oregon Health Sciences University - Internal Medicine

Research Grants

NIH Grants:  2 R01s, P01, T32

Research Summary

Mark Gladwin, MD has a long history of leadership of translational projects and programs. He currently serves as co-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. Dr. Gladwin’s basic and translational research has led to the development and licensing of intravenous and inhaled nitrite as a human therapeutic, with the recent completion of animal toxicology, GMP formulations, and phase Ia and Ib clinical trials. Phase II trials of inhaled nitrite are now underway. 

A central passion of Dr. Gladwin’s is to train the next generation of physicians and scientists in basic and translational research. He has a demonstrated commitment to training and education, and has trained students at many levels including pre-medical students participating yearly in the NIH Intramural Research Training Program, the Howard Hughes young investigator program, the Intramural Clinical Research Training Program, and many successful academic physician-scientists coming out of Pulmonary, Critical Care, Surgical, and Hematology Fellowship Programs. He has been very successful at mentoring these trainees to independent careers in academic medicine. Dr. Gladwin has mentored many to intramural funded faculty positions or extramural K or R awards. He has also mentored pre-doctoral students who have matriculated into both PhD and MD programs. Dr. Gladwin’s publications number well over 150 with current or past trainees as the first author. Dr. Gladwin is currently the PI of an NIH T32 training grant and previously directed another T32 while he was Division Chief of Pulmonary, Allergy and Critical Care Medicine at the University of Pittsburgh.

Representative Publications

  1. Hughan KS, Wendell SG, Delmastro-Greenwood M, Helbling N, Corey C, Bellavia L, Potti G, Grimes G, Goodpaster B, Kim-Shapiro DB, Shiva S, Freeman BA, Gladwin MT. Conjugated Linoleic Acid Modulates Clinical Responses to Oral Nitrite and Nitrate. Hypertension. 2017 Jul 24. pii: HYPERTENSIONAHA.117.09016. PMC5783786
  2. Rose JJ, Nolley E, Gladwin MT. A 53-Year-Old Woman with Severe Carbon Monoxide Poisoning. Ann Am Thorac Soc. 2017 Sep;14(9):1475-1478. doi: 10.1513/AnnalsATS.201701-002CC. PMID: 28862502
  3. Kato GJ, Steinberg MH, Gladwin MT. Intravascular hemolysis and the pathophysiology of sickle cell disease. J Clin Invest. 2017 Mar 1;127(3):750-760. PMC5330745
  4. Gladwin MT. Cardiovascular complications and risk of death in sickle-cell disease. Lancet. 2016 Jun 18;387(10037):2565-74.
  5. Osei-Hwedieh DO, Kanias T, St. Croix C, Jessup M, Xiong Z, Sinchar D, Franks J, Xu Q, Novelli EM, Sertorio J, Potoka K, Binder RJ, Basu S, Belanger M, Kim-Shapiro DB, Triulzi D, Lee JS, Gladwin MT. Sickle cell trait increases storage hemolysis and RBC post-transfusion clearance in mice. EBioMedicine. 11, 239-248, 2016. PMC5049931
  6. Simon MA, Vanderpool RR, Nouraie M, Bachman TN, White PM, Sugahara M, Gorcsan J 3rd, Parsley EL, Gladwin MT. JCI Insight. 2016 Nov 3;1(18):e89620. PMC5085611
  7. Corti P, Xue J, Tejero J, Wajih N, Sun M, Stolz DB, Tsang M, Kim-Shapiro DB, Gladwin MT. Globin X is a six-coordinate globin that reduces nitrite to nitric oxide in fish red blood cells. Proc Natl Acad Sci U S A. 2016 Jul 12. pii: 201522670. PMC4968712
  8. Azarov I, Wang L, Rose JJ, Xu Q, Huang XN, Belanger A, Wang Y, Guo L, Liu C, Ucer KB, McTiernan CF, O'Donnell CP, Shiva S, Tejero J, Kim-Shapiro DB, Gladwin MT. Five-coordinate H64Q neuroglobin as a ligand-trap antidote for carbon monoxide poisoning. Sci Transl Med. 2016 Dec 7;8(368):368ra173. PMC5206801
  9. Lai YC, Tabima DM, Dube JJ, Hughan KS, Vanderpool RR, Goncharov DA, St Croix CM, Garcia-Ocaña 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 Feb 23;133(8):717-31. doi: 10.1161/CIRCULATIONAHA.115.018935. Epub 2016 Jan 26. PMC4766041
  10. Gladwin MT, O'Donnell CP. Training pulmonary researchers to span the bench-to-bedside "Valley of Death". Am J Respir Crit Care Med. 2014 Nov 1;190(9):977-80. doi: 10.1164/rccm.201405-0822ED. PMID: 25360728
  11. 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. ATS Ad Hoc Committee on Pulmonary Hypertension of Sickle Cell Disease. Am J Respir Crit Care Med. 2014 Mar 15;189(6):727-40. doi: 10.1164/rccm.201401-0065ST PMC3983842
  12. Sparacino-Watkins CE, Tejero J, Sun B, Gauthier MC, Thomas J, Ragireddy V, Merchant BA, Wang J, Azarov I, Basu P, Gladwin MT. Nitrite reductase and NO synthase activity of the mitochondrial molybdopterin enzymes mARC1 and mARC2. J Biol Chem. Epub 2014 Feb 5. 2014 Apr 11;289(15):10345-58 ] PMID: 24500710. PMCID: PMC4036158