In our recently published work, we discovered that CUB-Domain-Containing Protein 1 (CDCP1) is a new and important ligand of CD6, which is a marker and a critical regulator of T cells, demonstrating a surprising role of CDCP1 in immune regulation. CDCP1 was originally discovered to be overexpressed on certain solid tumor cells, regulating tumor-cell anoikis resistance. However, the distribution of CDCP1 in the eye and its potential role in tissue homeostasis was unknown. In our latest (unpublished) work, using CDCP1 knockout (KO) mice and CDCP1 knocked down human corneal epithelial cells, we discovered that CDCP1 is highly and selectively expressed on corneal epithelial cells among all ocular cells, and that CDCP1 is critical for enhancing corneal wounding healing. In this proposed project, using the unique reagents and models that we have developed, including CDCP1-KO mice, CD6-KO mice, CDCP1-KO human corneal epithelial cells and recombinant mutant CDCP1 proteins, we will elucidate both the intrinsic and extrinsic mechanisms by which CDCP1 enhances corneal wound healing. We will also test novel CDCP1-targeted approaches as new therapeutics for accelerating corneal wound healing. The proposed work would establish a previously unknown role of CDCP1 in corneal wound healing, facilitate the development of new and effective therapies for this corneal pathological condition, and open a new avenue for research on CDCP1 and corneal homeostasis.

Public Health Relevance

This project will investigate the newly discovered roles of CDCP1 in regulating corneal wound healing and P. aeruginosa infection, which would facilitate the development of novel therapeutics for treating corneal pathological conditions such as impaired corneal wound healing and P. aeruginosa keratitis.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY030111-01
Application #
9714534
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Mckie, George Ann
Project Start
2019-04-01
Project End
2023-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Cleveland Clinic Lerner
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
135781701
City
Cleveland
State
OH
Country
United States
Zip Code
44195