# Membrane repair boosted by caspase signaling

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $626,750

## Abstract

Abstract
Cells undergo several types of regulated cell death, often initiated by proteases in the caspase family. Once
initiated, regulated cell death activates multiple processes in the cell in order to accomplish the demise of the
cell in a regulated fashion. For example, intestinal epithelial cells undergo the process of extrusion, whereby
the cell is detached from the epithelial monolayer and ejected into the lumen of the intestine. The process of
extrusion takes about 10 minutes, and requires that the extruding cell actively participate in the process by
disassembling its cytoskeleton, reassembling a contractile actomyosin ring, and then constricting and
disassembling adhesions to neighboring cells. Thus, the cell must remain alive for about 10 minutes, and
during that short time it must complete what we term a “bucket list” of tasks that accomplish the extrusion
process. Similarly, cells undergoing apoptosis activate multiple cellular processes to disassemble cellular
structures and package them into apoptotic blebs. This takes perhaps 30-60 minutes, the time in which the cell
must complete a bucket list of apoptotic tasks. Failure to complete these bucket lists will result in a defective
form of cell death that can be pathological. We recently discovered that caspase-7, once thought to be a cell
death executioner, is actually a death delaying caspase that buys the cell time to complete these bucket lists.
Caspase-7 hyperactivates the acid sphingomyelinase membrane repair pathway, allowing dying cells to more
efficiently repair damage to their membranes. Here we study the molecular mechanisms that enable caspase-7
to accomplish this unique function.

## Key facts

- **NIH application ID:** 10851067
- **Project number:** 1R01AI181815-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Edward A Miao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $626,750
- **Award type:** 1
- **Project period:** 2024-01-24 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10851067

## Citation

> US National Institutes of Health, RePORTER application 10851067, Membrane repair boosted by caspase signaling (1R01AI181815-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10851067. Licensed CC0.

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