# Decoding the mechanisms of cell-cell fusion

> **NIH NIH R35** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $21,427

## Abstract

PROJECT SUMMARY/ABSTRACT
Cell-cell fusion is critical to the conception, development and physiology of multicellular organisms, and is
involved in a variety of biological processes, such as fertilization, myogenesis, placenta development, bone
remodeling, immune response, tumorigenesis, and aspects of stem cells-mediated tissue regeneration.
Failure in cell fusion leads to defects such as infertility, congenital myopathy, osteopetrosis, immune
deficiency, and pre-eclampsia. A mechanistic understanding of cell fusion is not only important for
fundamental biology but may also provide basis for its manipulation in therapeutic settings. My lab has
been using Drosophila myoblast fusion as a model to study the general mechanisms underlying cell fusion.
We have made an unprecedented discover that cell fusion is an asymmetric process in which one cell
(attacking cell) invades its fusion partner (receiving cell) using actin-propelled membrane protrusions to
promote fusion pore formation. Building on insights we learned from myoblast fusion in vivo, we have
reconstituted high-efficiency cell fusion in an otherwise non-fusogenic, non-muscle cell line and uncovered
a novel function for invasive membrane protrusions in fusogen engagement. Furthermore, we have
discovered dynamic mechanosensory responses in the receiving fusion partner and demonstrated that
mechanical tension is a driving force for cell fusion. Our studies to date have provided significant insights
into the function of the actin cytoskeleton in promoting cell membrane juxtaposition and fusion. In the next
five years, we will expand our research into two new directions. First, we will extrapolate the mechanisms
that we uncovered in Drosophila to mammals and investigate the potential function of the actin
cytoskeleton in mammalian cell fusion, as well as how transmembrane fusogenic proteins coordinate with
the actin cytoskeleton to promote cell fusion. Second, we will identify and characterize novel
transmembrane proteins, including new fusogens, in cell fusion using the reconstituted cell-fusion culture
system as a model. We will continue to use an interdisciplinary approach including genetics, molecular
biology, biochemistry, biophysics, live imaging, super-resolution microscopy and electron microscopy in our
proposed research. By expanding from Drosophila to mouse, and from the actin cytoskeleton to
transmembrane proteins, our research will not only gain major new insights into the fundamental principles
of cell-cell fusion, but also have far-reaching impact on a broad range of fields, including membrane
biology, cell biology and developmental biology.

## Key facts

- **NIH application ID:** 10595802
- **Project number:** 3R35GM136316-03S1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Elizabeth H Chen
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $21,427
- **Award type:** 3
- **Project period:** 2020-05-04 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10595802

## Citation

> US National Institutes of Health, RePORTER application 10595802, Decoding the mechanisms of cell-cell fusion (3R35GM136316-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10595802. Licensed CC0.

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