This is a revised application for continued support of a programmatic, multi-disciplinary project aimed at investigating the regulation and adaptation of gastrointestinal (GI) function. The objectives of the first project (P.I.: G.A. Castro) are to further our understanding of how the mucosal immune system regulates epithelial cell and smooth muscle functions in the gastrointestinal tract and its role in physiological adaptations and maladaptations. The objectives of the second project (P.I.: Mari K. Haddox) are to elucidate the biochemical and molecular mechanisms responsible for expression and regulation of ornithine decarboxylase activity in gastrointestinal epithelia. The third project (P.I.: L.R. Johnson) is a logical extension of the P.I.'s efforts during the past five years to elucidate the roles of ornithine decarboxylase and polyamines in cell division, cell migration and cell-substrate interactions that are essential for the healing processes in response to mucosal damage. All of these projects will require the continued use of the Computational Core (C) supported by our current PPG Award and extensive use of a newly-established Cytobiology Core (B); the Administrative Core (A) will provide secretarial services and financial management for the research projects and scientific cores. The proposed studies involve a multidisciplinary approach aimed at resolving important questions at the molecular, cellular, tissue and organ levels. The unifying theme of these studies is to further our understanding of how the gastrointestinal tract adapts to environmental stresses in an integrative fashion.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK037260-09
Application #
2140043
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1986-07-21
Project End
1997-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
9
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Physiology
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Ray, Ramesh M; Patel, Anami; Viar, Mary Jane et al. (2002) RhoA inactivation inhibits cell migration but does not mediate the effects of polyamine depletion. Gastroenterology 123:196-205
Wang, J Y; Viar, M J; Li, J et al. (1998) Differences in transglutaminase mRNA after polyamine depletion in two cell lines. Am J Physiol 274:C522-30
Santos, M F; McCormack, S A; Guo, Z et al. (1997) Rho proteins play a critical role in cell migration during the early phase of mucosal restitution. J Clin Invest 100:216-25
Wang, J Y; Viar, M J; Li, J et al. (1997) Polyamines are necessary for normal expression of the transforming growth factor-beta gene during cell migration. Am J Physiol 272:G713-20
Santos, M F; Viar, M J; McCormack, S A et al. (1997) Polyamines are important for attachment of IEC-6 cells to extracellular matrix. Am J Physiol 273:G175-83
Wang, J Y; McCormack, S A; Johnson, L R (1996) Role of nonmuscle myosin II in polyamine-dependent intestinal epithelial cell migration. Am J Physiol 270:G355-62
Banan, A; Wang, J Y; McCormack, S A et al. (1996) Relationship between polyamines, actin distribution, and gastric healing in rats. Am J Physiol 271:G893-903
Mayorga-Wark, O; Dubinsky, W P; Schultz, S G (1996) Reversal of glibenclamide and voltage block of an epithelial KATP channel. Am J Physiol 271:C1122-30
Harari, Y; Grossie Jr, V B; Castro, G A (1996) Nutritional support for adaptation to radiation-induced suppression of mucosal immunity in the intestine of the rat. Radiat Res 145:754-61
Mayorga-Wark, O; Dubinsky, W P; Schultz, S G (1995) Reconstitution of a KATP channel from basolateral membranes of Necturus enterocytes. Am J Physiol 269:C464-71

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