# Structure function studies in intestinal epithelial JAM

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $486,750

## Abstract

ABSTRACT
This proposal lends strong support to the new concept of tight junction associated proteins as key
regulators of epithelial homeostasis in the intestine. It is now appreciated that tight junction (TJ)
proteins are not static barrier forming units, but act as dynamic signaling centers to fine tune many
critical epithelial cellular functions ranging including proliferation, migration and cell survival. Indeed,
inflammatory conditions such as ulcerative colitis and crohns disease are associated with a leaky gut,
epithelial proliferation and impaired wound healing/mucosal ulceration that is, in part, related to altered
expression of tight junction proteins. Pertinent to this project, we have compelling evidence of the
importance of TJ associated CTX proteins, junctional adhesion molecule A (JAM-A) and CAR Like
Membrane Protein (CLMP), that play complementary roles in the regulation of mucosal homeostasis by
promoting epithelial barrier function and downregulating IEC proliferative responses. Intriguingly, we
have observed reduced JAM-A in epithelial cell-cell contacts under inflammatory conditions while
CLMP expression, in contrast, is enhanced, suggesting coordinated fine tuning of CTX-dependent
epithelial responses under conditions of perturbed homeostasis.The goal of this proposal is centered on
elucidating fundamental mechanisms of how JAM-A and CLMP regulate crucial epithelial barrier
function and cellular proliferation. In Aims 1 and 2, we will extend preliminary findings that identify new
signaling elements controlling JAM-A-mediated regulation of barrier and epithelial proliferation,
respectively. In aim 3, with new inducible, tissue targeted knockout mice, we will define, for the first
time, the role of CLMP in regulation of epithelial barrier function and proliferation. The proposed studies
will not only shed new light into mechanisms of outside-in signaling at the TJ that regulate permeability
and proliferation, but may also provide new ideas for therapeutic targets with diverse applications
ranging from enhanced vaccine/drug delivery to wound healing/anti-inflammation or inhibition of cancer
progression.

## Key facts

- **NIH application ID:** 10145658
- **Project number:** 5R01DK061379-18
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** CHARLES A PARKOS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $486,750
- **Award type:** 5
- **Project period:** 2002-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145658

## Citation

> US National Institutes of Health, RePORTER application 10145658, Structure function studies in intestinal epithelial JAM (5R01DK061379-18). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10145658. Licensed CC0.

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