# A novel regulator of Pseudomonas aeruginosa keratitis

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2020 · $565,004

## Abstract

ABSTRACT
 CD6 is a critical regulator of T cells that is present on all T cells including γδ T cells. In our recently
published work, we discovered that CUB-Domain-Containing Protein 1 (CDCP1) is a new and important ligand
of CD6. This new discovery demonstrated a surprising role of CDCP1 in immune regulation. CDCP1 was
originally discovered as an overexpressed transmembrane protein on certain solid tumor cells intrinsically
regulating tumor-cell anoikis resistance. However, the distribution of CDCP1 in the eye and its potential role in
ocular immunity and tissue homeostasis were unknown. In our latest (unpublished) work, we used primary
human and mouse corneal epithelial cells, as well as CDCP1- and CD6-knockout (KO) mice, to demonstrate for
the first time that CDCP1 is highly and selectively expressed on normal corneal epithelial cells among all ocular
cells, and that CDCP1 is critical for controlling P. aeruginosa corneal infection, whose underlying mechanisms
integrally involve CD6-expressing γδ T cells. In this proposed project, we will use unique reagents and models
that we have developed, including CDCP1-KO mice, CD6-KO mice, γδ T cell-deficient mice, CDCP1-KO human
corneal epithelial cells and recombinant CDCP1 proteins, to elucidate both intrinsic and extrinsic mechanisms
by which CDCP1 controls bacterial infection of the cornea. We will also test novel CDCP1-targeted approaches
as new therapeutic strategies for managing P. aeruginosa keratitis. The proposed work is expected to establish
a previously unknown role of CDCP1 in the pathogenesis of P. aeruginosa keratitis, facilitate the development
of new and effective therapies for this painful and blinding disease, and open a new avenue for research on
CDCP1 in corneal immunohomeostasis.

## Key facts

- **NIH application ID:** 9958876
- **Project number:** 1R01EY031463-01
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** FENG C LIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $565,004
- **Award type:** 1
- **Project period:** 2020-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9958876

## Citation

> US National Institutes of Health, RePORTER application 9958876, A novel regulator of Pseudomonas aeruginosa keratitis (1R01EY031463-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9958876. Licensed CC0.

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