Abstract

This proposal deals with in depth investigation on the mechanisms responsible for pulmonary injury, pulmonary ischemia-reperfusion and specifically in orthotopic lung transplants in rats. The principal investigator has amassed an impressive body of preliminary data to support his hypothesis that reduced endothelial nitric oxide coupled with enhanced exppression of endothelial cell adhesion molecules are major factors in lung graft failure and pulmonary reperfusion injury. There are three specific aims.
Specific Aim 1 is to evaluate the role of the cAMP and cGMP pathways in maintaining pulmonary integrity.
Specific Aim 2 is to evaluate the role of neutrophil recruitment and particularly the actions of P-selectin expression on the vascular endothelium.
Specific Aim 3 is to determine optimal conditions for lung preservation and particularly to develop an improved preservation solution which preserves the vascular endothelium so that transplants can be successful.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL055397-04
Application #
6043870
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1996-08-01
Project End
2000-07-31
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032

  Publications

Park, Jason; Wrzesinski, Stephen H; Stern, Eric et al. (2012) Combination delivery of TGF-? inhibitor and IL-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy. Nat Mater 11:895-905
Badri, Linda; Murray, Susan; Liu, Lyrica X et al. (2011) Mesenchymal stromal cells in bronchoalveolar lavage as predictors of bronchiolitis obliterans syndrome. Am J Respir Crit Care Med 183:1062-70
Badri, Linda; Walker, Natalie M; Ohtsuka, Takashi et al. (2011) Epithelial interactions and local engraftment of lung-resident mesenchymal stem cells. Am J Respir Cell Mol Biol 45:809-16
Hasegawa, Tomomi; Okada, Kenji; Okita, Yutaka et al. (2011) Antioxidant properties of pioglitazone limit nicotinamide adenine dinucleotide phosphate hydrogen oxidase and augment superoxide dismutase activity in cardiac allotransplantation. J Heart Lung Transplant 30:1186-96
Liao, Hui; Hyman, Matthew C; Baek, Amy E et al. (2010) cAMP/CREB-mediated transcriptional regulation of ectonucleoside triphosphate diphosphohydrolase 1 (CD39) expression. J Biol Chem 285:14791-805
Hasegawa, Tomomi; Iwanaga, Koichiro; Hultquist, Donald E et al. (2009) Suppression of nitrosative and oxidative stress to reduce cardiac allograft vasculopathy. Am J Physiol Heart Circ Physiol 296:H1007-16
Stern, Eric; Jay, Steven M; Demento, Stacey L et al. (2009) Spatiotemporal control over molecular delivery and cellular encapsulation from electropolymerized micro- and nanopatterned surfaces. Adv Funct Mater 19:2888-2895
Heeba, G; Moselhy, M E; Hassan, M et al. (2009) Anti-atherogenic effect of statins: role of nitric oxide, peroxynitrite and haem oxygenase-1. Br J Pharmacol 156:1256-66
Diaz, J A; Booth, A J; Lu, G et al. (2009) Critical role for IL-6 in hypertrophy and fibrosis in chronic cardiac allograft rejection. Am J Transplant 9:1773-83
Hasegawa, Tomomi; Bouis, Diane; Liao, Hui et al. (2008) Ecto-5'nucleotidase (CD73)-mediated adenosine generation and signaling in murine cardiac allograft vasculopathy. Circ Res 103:1410-21

Showing the most recent 10 out of 86 publications