Faculty Bio - Bruce R Pitt, Ph.D.
Professor and EOH Chair
Bridgeside Point, 100 Technology Drive
Room 555, BRIDG
Pittsburgh, PA 15219-3130
Phone: (412) 624-8400
Personal Web Page
Dr. Pitt's laboratory efforts are directed towards original studies on the molecular and cellular biology of lung. To date, this work has focused primarily on the role of oxidants and nitric oxide in affecting pulmonary endothelial and vascular smooth muscle cell function. Isolated primary cell cultures, genetically modified murine models and somatic gene transfer to lung have been used as model systems to identify the role of partially reduced oxygen and nitrogen species in the response of the lung to stress and injury.
Recent efforts have been directed towards understanding the role of S-nitrosylation of the metal binding intracellular protein, metallothoinein, on zinc homeostasis and endothelial cell function. These studies are aided by a number of microspectrofluorometric approaches including a green fluorescent protein modified chimera of metallothionein, suitable for fluorescence resonance energy transfer, as outlined in the schema below. This chimera contains an enhanced cyan fluorescent protein (ECYP) that serves as a donor for an enhanced yellow flourescence protein (EYFP) that are fused to the N- and C-termini respectively of human metallothionein Iia (hMTIIa). The result of these live cell fluorescence image studies has identified a unique role for metallothionein in NO mediated zinc release. NO mediated changes in labile zinc appear to be inhibitory in proapoptotic conditions in pulmonary endothelial cells contributing to the notion that S-nitrosylation of zinc sulfur clusters is an important component of NO signaling.
In collaboration with Song Li, M.D., in School of Pharmacy, non viral vectors capable of being targeted to pulmonary endothelium for somatic gene transfer of plasmid DNA or oligonucleotides are being developed. An example of transgene expression of the reporter molecule, beta galactosidase, in murine lung is shown in the figure below. Enhanced efficiency and greatly improved targeting to pulmonary endothelium has been accomplished by including an anti-PECAM antibody to the quaternary complex. This also results in minimizing toxicity and provides rational approach to pharmacogenetic therapy for pulmonary vascular disease such as pulmonary hypertension or acute lung injury.
- Tyurina YY, Basova LV, Knoduru NV, Tyurin VA, Potapovich AI, Cai P, Bayir H, Stoyanovsky D, Pitt BR, Shvedova AA, Fadeel B and Kagan VE.
Nitrosative stress inhibits the aminophospholipid translocase resulting in phosphatidylserine externalizationand macrophage engulfment: implications for the resolution of inflammation.
J. Biol. Chem 282: 8498-8509, 2007. PMID: 17229723
- Li J, Wilson A, Kuruba R, Zhang Q, Gao X, He F, Zhang LM, Pitt BR, Xie W, Li S.
FXR-mediated regulation of eNOS expression in vascular endothelial cells.
Cardiovasc Res. 2007 Oct 19. PMID: 18006476
- Zhang Q, He F, Kuruba R, Gao X, Wilson A, Li J, Billiar TR, Pitt BR, Xie W, Li S.
FXR-Mediated Regulation of Angiotensin Type 2 Receptor Expression in Vascular Smooth Muscle Cells.
Cardiovasc Res. 2007 Nov 13. PMID: 1800643
- Fattman CL, Gambelli F, Hoyle GW, Pitt BR, Ortiz LA.
Epithelial expression of TIMP1 does not alter sensitivity to bleomycin-induced lung injury in C57BL/6 mice.
Am J Physiol Lung Cell Mol Physiol. 2008 Jan 4; PMID: 18178676
- Kleinschmidt AM, Nassiri M, Stitt MS, Wasserloos K, Watkins SC, Pitt BR, Jahroudi N.
Sequences in intron 51 of the von Willebrand factor gene target promoter activation to a subset of lung endothelial cells in transgenic mice.
J Biol Chem. 2008 Feb 1; 283 ( 5 ): 2741-50. Epub 2007 Nov 28. PMID: 18048367
- Kaynar AM, Houghton AM, Lum EH, Pitt BR, Shapiro SD.
Neutrophil Elastase Is Needed for Neutrophil Emigration into Lungs in Ventilator-Induced Lung Injury.
Am J Respir Cell Mol Biol. 2008 Feb 14; PMID: 18276796
- Bernal PJ, Leelavanichkul K, Bauer E, Cao R, Wilson A, Wasserloos KJ, Watkins SC, Pitt BR, St Croix CM
Nitric oxide mediated zinc release contributes to hypoxic regulation of pulmonary vascular tone.
Circ Res. 2008 May 15. PMID: 18483408
- Nemec AA, Leikauf G, Pitt BR, Wasserloos KJ, Barchowsky A.
Nickel Mobilizes Intracellular Zinc to Induce Metallothionein in Human Airway Epithelial Cells.
Am J Respir Cell Mol Biol. 2008 Dec 18. PMID: 19097988
- Kagan VE, Bayir HA, Belikova NA, Kapralov O, Tyurina YY, Tyurin VA, Jiang J, Stoyanovsky DA, Wipf P, Kochanek PM, Greenberger JS, Pitt B, Shvedova AA, Borisenko G.
Cytochrome c/cardiolipin relations in mitochondria: A kiss of death.
Free Radic Biol Med. 2009 Mar 11. PMID: 19285551
- Tyurin VA, Tyurina YY, Jung MY, Tungekar MA, Wasserloos KJ, Bayir H, Greenberger JS, Kochanek PM, Shvedova AA, Pitt B, Kagan VE.
Mass-spectrometric analysis of hydroperoxy- and hydroxy-derivatives of cardiolipin and phosphatidylserine in cells and tissues induced by pro-apoptotic and pro-inflammatory stimuli.
J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Mar 13. PMID: 19328050
- Tyurina YY, Tyurin VA. Kaynar M., Kapralova VI, Wasserloos K, Li J, Mosher M, Wright L, Wipf, P, Watkins S, Pitt BR, and Kagan VE.
Oxidative lipidomics of hyperoxic acute lung injury:Mass-spectrometric characterization of cardiolipin and phosphatidylserine peroxidation.
Am. J. Physiol: Lung Cell Mol Physiol. 2010 Jul;299(1):L73-85. Epub 2010 Apr 23. PMID: 20418384
- Szczepaniak WS, Pitt BR and McVerry BJ.
S1P2 receptor dependent Rho-kinase activation mediates vasoconstriction in the pulmonary circulation induced by sphingosine 1-phosphate.
Am. J. Physiol: Lung Cell Mol Physiol. 2010 Jul;299(1):L137-45. Epub 2010 Apr 30. PMID: 20435688
- Li H, Su X, Yan X, Wasserloos K, Chao W, Kaynar AM, Liu ZQ, Leikauf GD, Pitt BR, Zhang LM.
Toll-like Receptor 4-Myeloid Differentiation Factor 88 Signaling Contributes to Ventilator-induced Lung Injury in Mice.
Anesthesiology. 2010 Jul 29. PMID: 20683250
- Li H, Cao R, Wasserloos KJ, Bernal P, Liu ZQ, Pitt BR, St Croix CM.
Nitric oxide and zinc homeostasis in pulmonary endothelium.
Ann N Y Acad Sci. 2010 Aug;1203:73-8. PubMed PMID: 20716286
- John E, Laskow TC, Buchser WJ, Pitt BR, Basse PH, Butterfield LH, Kalinski P, Lotze MT.
Zinc in innate and adaptive tumor immunity.
J Transl Med. 2010 Nov 18;8:118. PMID: 21087493
- Phillippi JA, Eskay MA, Kubala AA, Pitt BR, Gleason TG.
Altered oxidative stress responses and increased type I collagen expression in bicuspid aortic valve patients.
Ann Thorac Surg. 2010 Dec;90(6):1893-8. PMID: 21095332
- Li HH, Xu J, Wasserloos KJ, Li J, Tyurina YY, Kagan VE, Wang X, Chen AF, Liu ZQ, Stoyanovsky D, Pitt BR, Zhang LM.
Cytoprotective effects of Albumin, Nitrosated or Reduced, in Cultured Rat Pulmonary Vascular Cells.
Am J Physiol Lung Cell Mol Physiol. 2011 Jan 14. PMID: 21239532
- Thambiayya K, Wasserloos KJ, Huang Z, Kagan VE, St Croix CM, Pitt BR.
LPS-induced decrease in intracellular labile zinc [Zni] contributes to apoptosis in cultured sheep pulmonary artery endothelial cells (SPAEC).
Am J Physiol Lung Cell Mol Physiol. 2011 Jan 14. PMID: 21239534
- Bernal PJ, Bauer EM, Cao R, Maniar S, Mosher M, Chen J, Wang QJ, Glorioso JC, Pitt BR, Watkins SC, St Croix CM.
A Role for Zinc in Regulating Hypoxia-Induced Contractile Events in Pulmonary Endothelium.
Am J Physiol Lung Cell Mol Physiol. 2011 Mar 4. PMID: 21378023
- Tyurina YY, Tyurin VA, Kapralova VI, Wasserloos K, Mosher M, Epperly MW, Greenberger JS, Pitt BR, Kagan VE.
Oxidative lipidomics of Υ-radiation-induced lung injury: mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation.
Radiat Res. 2011 May;175(5):610-21. Epub 2011 Feb 21. PMID:21338246
- Cambal LK, Swanson MR, Yuan Q, Weitz AC, Li HH, Pitt B, Peterson J, Pearce LL.
Acute, Sub-lethal Cyanide Poisoning in Mice is Ameliorated by Nitrite Alone: Complications Arising from Concomitant Administration of Nitrite and Thiosulfate as an Antidotal Combination.
Chem Res Toxicol. 2011 Jul 18;24(7):1104-12. Epub 2011 May 11. PMID:21534623
- Pitt BR, Christman JW, Gunst SJ, Matthay MA, Stevens T, Ware LB.
Physiology, reductionism, and translational medicine: the right mix.
Am J Physiol Lung Cell Mol Physiol. 2011 Oct;301(4):L389-90. Epub 2011 Aug 19. No abstract available. PMID:21856812
- Atkinson J, Kapralov AA, Yanamala N, Tyurina YY, Amoscato AA, Pearce L, Peterson J, Huang Z, Jiang J, Samhan-Arias AK, Maeda A, Feng W, Wasserloos K, Belikova NA, Tyurin VA, Wang H, Fletcher J, Wang Y, Vlasova II, Klein-Seetharaman J, Stoyanovsky DA, Bayîr H, Pitt BR, Epperly MW, Greenberger JS, Kagan VE.
A mitochondria-targeted inhibitor of cytochrome c peroxidase mitigates radiation-induced death.
Nat Commun. 2011 Oct 11;2:497. doi: 10.1038/ncomms1499. PubMed PMID: 21988913
- Gorbunov NV, Atkins JL, Gurusamy N, Pitt BR.
Iron-induced remodeling in cultured rat pulmonary artery endothelial cells.
Biometals. 2012 Feb;25(1):203-17. Epub 2011 Nov 17. PMID:22089858
- Thambiayya K, Wasserloos KJ, Kagan VE, Stoyanovsky D, Pitt BR.
A critical role for increased labile zinc in reducing sensitivity of cultured sheep pulmonary artery endothelial cells to LPS-induced apoptosis.
Am J Physiol Lung Cell Mol Physiol. 2012 Apr 20. PMID: 22523284
- Cioffi DL, Wu S, Chen H, Alexeyev M, St Croix CM, Pitt BR, Uhlig S, Stevens T.
Orai1 Determines Calcium Selectivity of an Endogenous TRPC Heterotetramer Channel.
Circ Res. 2012 Apr 24. PMID: 22534489
- BA Brown University
- Ph.D. Environmental Health Science, Johns Hopkins University School Hygiene and Public Health