Subglottic and tracheal stenosis can lead to high morbidity and mortality of individuals, due to limited airflow. Two forms of stenosis exist, congenital, caused by abnormal development of the trachea, and acquired, usually due to iatrogenic causes. The study of subglottic and tracheal stenosis has been limited to gross morphologic descriptions of inadequate airways. Surgical correction remains challenging, often with poor results. The principal investigator has a strong interest in the prevention and treatment of pediatric airway abnormalities. The proposed projects represent a rare opportunity to investigate both forms of tracheal stenosis using immunohistochemical and gene identification techniques. Support for this project will allow the principal investigator to develop the needed basic science expertise to make significant improvements to existing techniques to prevent and treat tracheal stenosis. The murine model will be used to test the hypothesis that regional tissue controls the growth and morphology of underlying tracheal cartilage. Individual study elements include 1) identification of growth influences of individual tissue layers that surround the tracheal cartilage 2) conditioned media experiments to test the influence of soluble proteins derived from epithelium and perichondrium on tracheal cartilage growth 3) identification of the proteins that control growth. Long-term goals of the principal investigator involve establishment of an independent research laboratory that can investigate hyaline cartilage growth and respiratory mucosal inflammation, and identify genes and their protein products that control tracheal morphology.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL070116-02
Application #
6750045
Study Section
Special Emphasis Panel (ZHL1-CSR-M (F2))
Program Officer
Colombini-Hatch, Sandra
Project Start
2003-05-19
Project End
2008-04-30
Budget Start
2004-05-01
Budget End
2005-04-30
Support Year
2
Fiscal Year
2004
Total Cost
$125,982
Indirect Cost
Name
Massachusetts Eye and Ear Infirmary
Department
Type
DUNS #
073825945
City
Boston
State
MA
Country
United States
Zip Code
02114
Baig, Samir M; Martinez-Alvernia, Efrain A; Mankarious, Leila A (2011) Immunoglobulin A defines secretions from salivary tissue in post-Sistrunk procedure drainage. Otolaryngol Head Neck Surg 144:888-90
Martinez-Alvernia, Efrain A; Mankarious, Leila A (2010) Matrix metalloproteinase inhibition causes luminal narrowing and ring thickening in the cricoid cartilage. Otolaryngol Head Neck Surg 142:510-5
Martinez-Alvernia, Efrain A; Mankarious, Leila A (2008) Matrix metalloproteinases 2 and 9 are concentrated in the luminal aspect of the cricoid cartilage, diminish with loss of perichondrium, and are reinstated by transforming growth factor beta 3. Ann Otol Rhinol Laryngol 117:925-30
Martinez-Alvernia, Efrain A; Rudnick, Jennifer A; Mankarious, Leila A (2008) Transforming growth factor beta3 increases chondrocyte proliferation and decreases apoptosis in murine cricoid cartilage in vitro. Otolaryngol Head Neck Surg 138:435-40