# Regulation and function of multicellular calcium signaling in epithelial growth and regeneration

> **NIH NIH R35** · UNIVERSITY OF NOTRE DAME · 2020 · $386,250

## Abstract

ABSTRACT
Many diseases including Alzheimer's, cardiac arrhythmias, and multiple metastatic cancers exhibit
dysregulated intercellular Ca2+ transients (ICTs). Calcium ions (Ca2+) serve as critical second messengers
involved in cell signaling and in coordinating proper organ development. Ca2+ is also important in the
transduction of mechanical forces in tissues and for integrating multiple biochemical signals from diffusible
proteins termed morphogens. Both morphogen signaling and mechanical force inputs have been implicated in
the size control and patterning of developing organs. However, much is still unknown about the regulation and
functions of ICTs during tissue growth and regeneration. For example, it has been known for some time that a
left-right asymmetry in intracellular Ca2+ concentrations exists during vertebrate development; however, the
exact mechanism governing this observed asymmetry remains unclear. The overall goal of the research
program is to identify the underlying principles and mechanisms that govern the coordination of cellular
processes during growth and regeneration with a particular emphasis on understanding the regulation and
functions of ICTs. Our lab is at the forefront of developing multi-disciplinary approaches to define the interplay
between ICTs, morphogen signaling, and mechanical forces during tissue growth and regeneration. We have
recently discovered anterior-posterior patterning of ICTs in developing Drosophila (fruit fly) wing discs. We
have identified that genetic disruption of the Hedgehog (Hh) pathway, which directs patterning of the anterior-
posterior axis in the wing primordium, abolishes this observed asymmetry of ICTs. This establishes a
fundamental link between morphogen signaling and ICTs in a developmental context. We are now currently
focused on bridging the large gap between descriptive observations and systems-level quantitative analysis of
ICTs. We are studying the impact of ICTs on morphogen signaling, organ development, and regeneration by
modulating ICTs and morphogen activity both genetically and pharmacologically in Drosophila wing discs.
Further, we are capturing dynamic and multi-scale measurements of ICTs to characterize modulators of Ca2+.
We are also developing computational models to test hypothesized cross-talk between morphogenetic
signaling and Ca2+ signaling dynamics. Cumulatively, this research will result in novel quantitative imaging
approaches to map ICTs to morphogenetic patterning in developing and regenerating tissues. A mechanistic
understanding of ICT regulation and function will lead to critical insights into how tissues grow and regenerate.
This fundamental understanding also will allow us to understand and mitigate unwanted side effects of
targeting Ca2+ signaling therapeutically and will potentially reveal innovative strategies for accelerating tissue
regeneration.

## Key facts

- **NIH application ID:** 9983722
- **Project number:** 5R35GM124935-04
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** Jeremiah James Zartman
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,250
- **Award type:** 5
- **Project period:** 2017-08-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983722

## Citation

> US National Institutes of Health, RePORTER application 9983722, Regulation and function of multicellular calcium signaling in epithelial growth and regeneration (5R35GM124935-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9983722. Licensed CC0.

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