# Pilot Project 4: Calcium (Dys)regulation in Smokers vs. E-cig users - Uniquely Targeting the Ca2+ Senor STIM1

> **NIH NIH U54** · NORTH CAROLINA CENTRAL UNIVERSITY · 2020 · $68,746

## Abstract

The long-term goal of this initiative is the interrogation of a novel mechanism of lung disease initiation and progression as relates to ecigarette
(E-Cig) use. We have found that the flavor constituents of many e-liquid (the actual product consumed/vaped by the E-Cig user,
which is composed of a propylene glycol (PG)/vegetable glycerin(VG) vehicle, any number of added flavoring constituents and +/-
nicotine), beyond nicotine itself, cause cytosolic Ca2+ responses. Additionally, a number (>25) of Ca2+ homeostasis and signaling
proteins, including the endoplasmic reticulum Ca2+ sensor STIM1 (stromal interacting molecule-1), are known to be upregulated due to
E-Cig, but NOT traditional cigarette, use.
As a sensor for the activation of store-operated Ca2+ entry (SOCE), STIM1 is a crucial regulator of Ca2+ homeostasis. Ca2+ itself
serves as a universal second messenger that not only controls apoptosis but also influences cell division/growth and gene expression.
Furthermore, abnormal Ca2+ homeostasis has been linked to several ailments, including airway inflammation, chronic obstructive
pulmonary disease (COPD), inflammatory bowel diseases and lung cancer. Growing evidence suggests that the molecular components
of SOCE (STIM1 and the Ca2+ channels that it regulates) play a crucial role in pulmonary disease initiation and progression, indicating
that SOCE inhibition is potentially therapeutic.
Based upon the available information laid out here, might E-Cig use lead to more aggressive/severe (in comparison to the use of
traditional cigarettes) lung disease in the future? This question cannot currently be answered since E-Cigs have only recently been
available to the population at large (~10 yrs). Because these products are so new, relatively little is known about their physicochemical
properties. Hence, the goals of the current proposal are to (Aim 1) demonstrate STIM1 protein upregulation as a result of E-Cig exposure
using a lung epithelial cell line (CALU-3) and to assess Ca2+ regulation/dysregulation in our cell line model (Aim 2). Completion of the
proposed Aims will ultimately shed light on the possible health implications of new and emerging tobacco products (such as E-Cigs),
provide mechanistic detail on the progression of lung disease in smokers vs. E-Cig users and deliver valuable data on a promising new
therapeutic target, STIM1.

## Key facts

- **NIH application ID:** 10247150
- **Project number:** 3U54CA156735-10S1
- **Recipient organization:** NORTH CAROLINA CENTRAL UNIVERSITY
- **Principal Investigator:** Rob U Onyenwoke
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $68,746
- **Award type:** 3
- **Project period:** 2010-09-29 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247150

## Citation

> US National Institutes of Health, RePORTER application 10247150, Pilot Project 4: Calcium (Dys)regulation in Smokers vs. E-cig users - Uniquely Targeting the Ca2+ Senor STIM1 (3U54CA156735-10S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10247150. Licensed CC0.

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