# TRPM7 at the Crossroads of Tissue Homeostasis and inflammation

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2022 · $367,990

## Abstract

In all organ systems, timely and non-inflammatory clearance of senescent, damaged and dead cells is a
crucial checkpoint at the crossroads of tissue homeostasis and inflammation. Through a specialized form of
phagocytosis, termed efferocytosis, the tissue-resident phagocytes recognize, engulf and digest cell corpses
without the inflammatory and self-destructive activation of the immune system. Efferocytosis of virally infected cell
corpses is also a prerequisite to antigen processing and presentation that lies at the heart of anti-viral
immunosurveillance. The mechanisms through which the engulfed corpses are digested in the efferophagosome
are highly dependent on Ca2+-signaling but underlying ion channel mechanisms have not been studied. Our
preliminary data indicates that the ion channel TRPM7 plays a crucial role in the maturation of the efferophagosome
and its ultimate fusion with the lysosomes. Pursuing these tantalizing leads has now laid a strong scientific
foundation to hypothesize that: Efferophagosome maturation is controlled by the fusion of M7Vs to the
efferophagosome and through TRPM7 channel activity in the efferophagosome membrane. In Aim 1, to establish
the physiological significance, we will interrogate TRPM7 function across three main forms of efferocytosis,
including its role in coordinating inflammatory signals. In Aim 2, we distill key insights about the nature and function
of TRPM7-containing vesicles in efferophagosome maturation. In Aim 3, we develop a mechanistic picture of how
TRPM7 is activated and how this activity controls efferophagosome maturation. This research is conceptually
innovative because it unravels new molecular machinery involving TRPM7 in the understudied process of
efferophagosome maturation. Our research is also the first thrust toward a complete biochemical characterization
of TRPM7-containing vesicles (M7Vs) and their cell biological function. Technical innovations include novel
transgenic/gene-edited mouse lines, and membrane fusion assays designed specifically to interrogate M7V-efferophagosome fusion. Deconstructing the efferophagosome in terms of its maturation stages, molecular
architecture, and biophysical/biochemical activities may advance TRPM7 as a drug target to modify tissue
regeneration and anti-viral immunity.

## Key facts

- **NIH application ID:** 10409807
- **Project number:** 5R01GM108989-07
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** BIMAL N. DESAI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $367,990
- **Award type:** 5
- **Project period:** 2016-01-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10409807

## Citation

> US National Institutes of Health, RePORTER application 10409807, TRPM7 at the Crossroads of Tissue Homeostasis and inflammation (5R01GM108989-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10409807. Licensed CC0.

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