Abstract

The long-term goal of this grant is to develop new approaches to improve vascular repair, control angiogenesis and aid wound healing by understanding the biological function of tissue transglutaminase (TTG). TTG is a unique wound-healing enzyme that displays many important biologic activities often overlooked when studying wound healing. There are many gaps in our knowledge of TTG structure and function that we plan to systematically investigate in this grant application.
In aim 1, we plan to investigate at what phase of wound healing TTG functions to promote tissue repair.
In aim 2, we will examine at what phase of wound healing TTG expression and function is needed using the TTG KO mouse model.
In aim3, we plan to investigate the role of the transglutaminase and NO binding activities of Mouse TTG on wound healing; and in aim 4, we plan to investigate whether TTG added to the fibrin chambers in a diabetic mouse model would overcome the documented wound healing defect that exists in diabetes mellitus. Understanding how TTG function in wound repair could lead to important advances in treating diseases such as diabetes with impair wound healing.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL072184-03
Application #
6922840
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Goldman, Stephen
Project Start
2003-09-01
Project End
2007-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
3
Fiscal Year
2005
Total Cost
$346,500
Indirect Cost

  Institution

Name
Duke University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Lai, Thung-S; Greenberg, Charles S (2013) Histaminylation of fibrinogen by tissue transglutaminase-2 (TGM-2): potential role in modulating inflammation. Amino Acids 45:857-64
Lai, Thung-S; Greenberg, Charles S (2013) TGM2 and implications for human disease: role of alternative splicing. Front Biosci (Landmark Ed) 18:504-19
Lai, Thung S; Davies, Christopher; Greenberg, Charles S (2010) Human tissue transglutaminase is inhibited by pharmacologic and chemical acetylation. Protein Sci 19:229-35
Lai, Thung-S; Liu, Yusha; Tucker, Tim et al. (2008) Identification of chemical inhibitors to human tissue transglutaminase by screening existing drug libraries. Chem Biol 15:969-78
Gupta, Madhu; Greenberg, Charles S; Eckman, Delrae M et al. (2007) Arterial vimentin is a transglutaminase substrate: a link between vasomotor activity and remodeling? J Vasc Res 44:339-44
Sane, David C; Kontos, Jimmy L; Greenberg, Charles S (2007) Roles of transglutaminases in cardiac and vascular diseases. Front Biosci 12:2530-45
Lai, Thung-S; Liu, Yusha; Li, Weidong et al. (2007) Identification of two GTP-independent alternatively spliced forms of tissue transglutaminase in human leukocytes, vascular smooth muscle, and endothelial cells. FASEB J 21:4131-43
Lai, T-S; Tucker, T; Burke, J R et al. (2004) Effect of tissue transglutaminase on the solubility of proteins containing expanded polyglutamine repeats. J Neurochem 88:1253-60