# Novel Roles of Sodium Hydrogen Exchanger 8 (NHE8) in Mucosal Homeostasis

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2020 · $345,375

## Abstract

Abstract
 This is a new application designed to study the novel roles of intestinal NHE8 on mucosal hemostasis. We
have made major discoveries in this field, being the first lab to clone and characterize its expression and transport
kinetics in 2005. We have described changes in postnatal expression of NHE8, defined its regulation by growth
factor and hormones, and (of importance for this proposal) described its abundant expression in the goblet cells
and colonic crypts. We developed NHE8-deficient mice (NHE8KO) and demonstrated fascinating phenotypes
ranging from the impaired gut mucosal integrity (defects in goblet and Paneth cells, enhanced susceptibility to
mucosal injury, microbial dysbiosis, increased bacterial adhesion and disruption of the mucus layer), to male
infertility and development of dry eye syndrome. These and additional preliminary observations presented in this
proposal led us to hypothesize that this transporter plays pleiotropic roles in mucosal homeostasis and that its
reduced expression in IBD contributes to intestinal inflammation and susceptibility to colorectal cancer. To test
this hypothesis, we formulated the following Aims:
Aim 1: Determine the mechanism of NHE8 involvement in goblet cell function
Aim 2: Characterize NHE8 expression in human UC patients and the microbial and
 inflammatory consequences of its loss
Aim 3: Determine the roles of NHE8 in tumorigenesis
 We expect that the planned studies will be transformative and lead to the creation of a new paradigm regard-
ing the role of epithelial Na+/H+ exchange, NHE8 in particular, in gut health.

## Key facts

- **NIH application ID:** 9980395
- **Project number:** 5R01DK113754-04
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Fayez Khalaf Ghishan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $345,375
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980395

## Citation

> US National Institutes of Health, RePORTER application 9980395, Novel Roles of Sodium Hydrogen Exchanger 8 (NHE8) in Mucosal Homeostasis (5R01DK113754-04). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/9980395. Licensed CC0.

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