# The Role of EMT signaling and ECM Stiffness in Cytokinetic Abscisssion

> **NIH NIH F30** · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · 2021 · $28,227

## Abstract

Project Summary:
 Cytokinetic abscission, the final stage of cell division, is a complex process that requires the assembly
of proteins in a sequential fashion to successfully sever the intercellular bridge that connects the two daughter
cells. Abscission failure generates multinucleated cells, which are observed in normal tissues, such as human
epidermis, myoblasts, and the terminal epithelium of a lactating mammary gland, as well as in several human
tumors, including those of the breast. Multinucleated cells that continue to divide will lead to aneuploidy, a sign
of chromosomal instability, underlining the importance of understanding how microenvironmental conditions
lead to abscission failure and multinucleation. We recently found that mammary epithelial cells induced to
undergo epithelial-mesenchymal transition (EMT) on stiff microenvironments, similar to what is found at the
terminal ends of a normal mammary gland or in breast tumors, fail to complete cytokinesis, resulting in
multinucleated cells. EMT signaling through Snail leads to an increase in the expression of septin-6, a filament-
forming GTPase that is recruited to the intercellular bridge, specifically the midbody, during cytokinesis. Cells
cultured on soft substrata do not upregulate septin-6 expression, fail to undergo EMT, and are able to undergo
normal abscission. I therefore hypothesize that ECM stiffness along with EMT signaling affects the ability of
Snail to bind to the promoter of septin-6 and affects the balance of factors required for normal abscission. I will
use synthetic microenvironments combined with assays to measure protein-DNA interactions as well as
imaging techniques to understand how Snail and the microenvironment disrupt abscission. In Specific Aim 1, I
will use chromatin immunoprecipitation (ChIP) assays, promoter-reporter assays, and sequencing (ChIP-seq
and RNA-seq) to determine how Snail and stiffness synergistically regulate expression of septin-6 in mammary
epithelial cells. In Specific Aim 2, I will combine synthetic substrata with quantitative imaging and timelapse
analysis to determine the mechanism by which stiff microenvironments and Snail alter abscission. Successfully
completing these aims will deepen our understanding of how the microenvironment regulates abscission
failure, which will provide additional insight into the process of cytokinesis and may also suggest therapeutic
targets for diseases associated with multinucleation. At the same time, this research plan synergizes with my
training plan within a multi-institutional MD/PhD environment, which will strengthen my understanding of
quantitative cell and molecular biology, as well as how this field informs and is informed by clinical practice in
internal medicine.

## Key facts

- **NIH application ID:** 10396266
- **Project number:** 7F30GM134602-03
- **Recipient organization:** RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
- **Principal Investigator:** Emann M Rabie
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $28,227
- **Award type:** 7
- **Project period:** 2020-01-01 → 2022-10-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10396266

## Citation

> US National Institutes of Health, RePORTER application 10396266, The Role of EMT signaling and ECM Stiffness in Cytokinetic Abscisssion (7F30GM134602-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10396266. Licensed CC0.

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