(Taken from the Candidate's Abstract) Acute or chronic exposure of environmental insults and toxicants trigger inflammatory pulmonary conditions, resulting in infiltration of inflammatory cells and elevation of inflammatory mediators, and alteration of the integrity and function of the airway epithelium. Hypersecreted visco-elastic mucus causes obstruction of central and peripheral airways in many inflammatory airway diseases such as asthma, cystic fibrosis, chronic bronchitis, and bronchiectasis. Inhibition of over expressed pathophysiologic mucus is one of the major targets for treatments of airway inflammatory disorders. Previously, the candidate has shown that tetinoic acid (RA), a key element required for mucous cell differentiation, mucin production, and mucin gene expression is mediated through retinoic acid receptor alpha. Based on these findings, the candidate hypothesizes that repressing receptor alpha activity will inhibit over expression of mucin gene mRNAs and mucin hypersecretion induced by inflammatory mediators.
The specific aims are to clarify: 1) the biochemical mechanisms by which inflammatory mediators increase the expression of mucin gene mRNAs and mucin secretion; 2) the molecular mechanisms by which receptor alpha signaling pathway regulate inflammatory mediators-increased mucin production; and, 3) the molecular mechanisms of a cross-talk between receptor alpha and IL-1 beta signaling pathways.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Career Transition Award (K22)
Project #
1K22ES000362-01
Application #
6132595
Study Section
Special Emphasis Panel (ZES1-LKB-C (K3))
Program Officer
Shreffler, Carol K
Project Start
2001-09-25
Project End
2004-07-31
Budget Start
2001-09-25
Budget End
2002-07-31
Support Year
1
Fiscal Year
2001
Total Cost
$102,692
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Surgery
Type
Other Domestic Higher Education
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030