# Regulation of alternative splicing during epithelial-mesenchymal transition

> **NIH NIH R35** · BAYLOR COLLEGE OF MEDICINE · 2022 · $400,000

## Abstract

ABSTRACT
 Alternative splicing of pre-mRNA enables a gene to give rise to multiple distinct mRNA transcripts,
yielding protein isoforms with different, even opposing, functions. The long-term goal of our research is to
understand the molecular mechanisms and function of alternative splicing on biological activities. The focus of
this proposal is to investigate the regulation of alternative splicing in epithelial-mesenchymal transition (EMT).
EMT is an essential developmental process that allows cells to change from a tightly packed cobble-stone-like
epithelial cellular state to a motile and spindle-shaped mesenchymal cellular state. When abnormally activated,
EMT promotes many types of diseases, including tissue fibrosis and cancer metastasis. Through working at the
intersection of RNA splicing and cell biology, my lab has made several important findings connecting RNA
regulation and EMT. Our work revealed, for the first time, that splice isoform switching of the CD44 gene causally
controls EMT. By manipulating CD44 alternative splicing, we were able to convert cells between the epithelial
and mesenchymal states. We have also identified the RNA-binding protein (RBP) hnRNPM as a critical splicing
factor that promotes EMT through the regulation of alternative splicing. These results suggest that RNA splicing
regulation could serve as an important mechanism that provides cellular plasticity. By shifting the programs of
alternative splicing, cells are able to convert between the epithelial and mesenchymal cellular states. This
capacity of reversing phenotypes is important for normal developmental EMT, as well as for cancer metastasis.
Major new discoveries are necessary to fully understand this phenomenon and its underlying mechanisms. Our
proposed research program is focused on (1) determining whether splice isoform switching acts as a prevalent
mechanism that drives EMT or, if it is largely a phenomenon of byproducts; (2) understanding how RBPs
precisely control alternative splicing during EMT; and (3) dissecting how signaling cascades elicit signals to RBPs
and trigger alternative splicing changes during EMT. We have made major efforts in the past several years to
build up experimental systems and gain expertise to help carry out our proposed studies. These efforts include
large-scale RNA profiling of alternative splicing in multiple EMT systems, bioinformatics and experimental
analysis of RBPs, as well as our recently completed kinase screen for EMT-associated alternative splicing
alterations. Accomplishing the proposed work will provide new insights into our understanding of the regulatory
mechanisms of alternative splicing, thus contributing to biological relevance in normal development and diseases.

## Key facts

- **NIH application ID:** 10364651
- **Project number:** 5R35GM131876-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Chonghui Cheng
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $400,000
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364651

## Citation

> US National Institutes of Health, RePORTER application 10364651, Regulation of alternative splicing during epithelial-mesenchymal transition (5R35GM131876-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10364651. Licensed CC0.

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