# Calcium entry modulates stem cell proliferation

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2020 · $192,500

## Abstract

Project Summary
Saliva performs a number of extremely important biological functions that are instrumental in maintaining oral
health. It has been estimated that more than 5 million people in the US suffers from salivary gland
dysfunctions that occurs as a results of various pathological conditions such as radiation therapy for head and
neck cancer and Sjögerns syndrome. Loss of saliva in these patients causes mastication and swallowing
difficulties, burning sensation to the mouth and dysgeusia. Although current treatment options reduce the
severity of the symptoms, they cannot restore acini function. Thus, efforts to restore salivary gland tissues are
of utmost importance for these patients. Importantly, stem cells have been suggested as possible source for
tissue regeneration; it has not been used for salivary gland regeneration. One of the major issues in using
stem cells for regeneration is that soon after introduction of these stem cells in an organ system, they start
differentiating, thereby not providing enough stem cells that can restore the organ function. Results obtained
from our ongoing studies indicate that loss of calcium entry induces stem cell differentiation, thereby inhibiting
stem cell proliferation. Furthermore we have identified that Ca2+ entry in mesenchymal stem cells is mediated
via the store-operated Ca2+ entry (SOCE) mechanism that is dependent on TRPC1-STIM1 interaction.
Importantly, overexpression of a mutant STIM1 construct (STIM1D76A) functionally interacts with TRPC1-Orai1
complex (plasma membrane Ca2+ channels that function as SOCE channels) and constitutively activates Ca2+
entry that is essential for cell proliferation. These results are novel, and suggest a strong relationship with
regard to changes in calcium handling that can promote proliferation, but they need to be further validated.
Therefore, in this grant proposal we intend to thoroughly characterize the role of changes in calcium signaling
and to determine if manipulation of these calcium signaling modulators can restore radiation induced
damaged salivary glands. The hypothesis of this study is that regulated Ca2+ entry can support c-kit positive
mesenchymal stem cell proliferation that can regenerate salivary gland cells and restore salivary secretion.
Thus, identification of the mechanism as well as the factors that lead to salivary gland restoration could
represent as new therapeutic options for patients that suffer from salivary gland dysfunction. We have initiated
collaboration with a group, who have developed this technique and will coordinate our efforts in order to
determine the functional significance of calcium channel in regulating stem cell proliferation and differentiation
to restore saliva secretion. We will coordinate our efforts in order to determine the functional significance of
mesenchymal stem cells in restoring salivary gland function. We will also investigate the mechanism and the
ion channels involved in stem cell proliferation/di...

## Key facts

- **NIH application ID:** 9948634
- **Project number:** 5R21DE028265-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Brij B Singh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $192,500
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948634

## Citation

> US National Institutes of Health, RePORTER application 9948634, Calcium entry modulates stem cell proliferation (5R21DE028265-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9948634. Licensed CC0.

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