This proposal describes a 5-year training program for the development of an academic career in surgery. The principal investigator has completed surgical training at Brown University and a research fellowship in tissue engineering at Harvard University and now, will expand upon his scientific skills through a unique integration of interdepartmental resources. This program will further develop the principal investigators command of tissue engineering techniques for the treatment of cardiovascular diseases. W. Mark Saltzman will mentor the principal investigator's scientific development. Dr. Saltzman is a recognized leader in the field of tissue engineering. He is chairman of the Department of Biomedical Engineering and has trained numerous postdoctoral fellows and graduate students. Jordan S. Pober will co-mentor the principal investigator's scientific development. Dr. Pober is a recognized leader in the field of vascular biology. He is director of the Interdepartmental Vascular Biology and Transplantation Program and has trained many postdoctoral fellows including a number of surgeon-scientists. In addition, an advisory committee of highly regarded medical scientists will provide scientific and career advice. Research will focus on development of tissue engineered vascular conduits for use in bypass surgery. In this proposal we will explore the application of both drug delivery and genetic engineering principles to the design of tissue engineered vascular conduits in an attempt to inhibit the formation of neointimal hyperplasia, a leading cause of vascular graft failure.
Specific aims i nclude: 1) Establishing a model for investigating the development of neointimal hyperplasia in tissue engineered vascular grafts in vivo, 2) Determining if controlled release of sirolimus (rapamycin) from the scaffold used to construct tissue engineered vascular conduits can inhibit the development of neointimal hyperplasia, and 3) Determining if overexpression of endothelial nitric oxide synthase (eNOS) by the cells used to create tissue engineered vascular conduits can inhibit the formation of neointimal hyperplasia. Yale University provides an ideal setting for training physician scientists by incorporating expertise from diverse resources into customized programs. Such an environment maximizes the potential for the principal investigator to establish a scientific niche from which an academic career can be constructed.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL083980-03
Application #
7433215
Study Section
Special Emphasis Panel (ZHL1-CSR-O (F1))
Program Officer
Commarato, Michael
Project Start
2006-06-01
Project End
2011-05-31
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
3
Fiscal Year
2008
Total Cost
$133,110
Indirect Cost
Name
Yale University
Department
Surgery
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Patterson, Joseph T; Gilliland, Thomas; Maxfield, Mark W et al. (2012) Tissue-engineered vascular grafts for use in the treatment of congenital heart disease: from the bench to the clinic and back again. Regen Med 7:409-19
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Hibino, Narutoshi; Villalona, Gustavo; Pietris, Nicholas et al. (2011) Tissue-engineered vascular grafts form neovessels that arise from regeneration of the adjacent blood vessel. FASEB J 25:2731-9
Mirensky, Tamar L; Hibino, Narutoshi; Sawh-Martinez, Rajendra F et al. (2010) Tissue-engineered vascular grafts: does cell seeding matter? J Pediatr Surg 45:1299-305
Roh, Jason D; Sawh-Martinez, Rajendra; Brennan, Matthew P et al. (2010) Tissue-engineered vascular grafts transform into mature blood vessels via an inflammation-mediated process of vascular remodeling. Proc Natl Acad Sci U S A 107:4669-74

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