# Mechanisms of SWI/SNF complex assembly and function

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $388,750

## Abstract

Project Summary
Chromatin remodeling complexes play a critical role in regulating gene expression, differentiation, and
development. The SWI/SNF chromatin remodeling complex is mutated in ~25% of all human tumors. The
12-15 positions within SWI/SNF are filled from ~30 unique subunits. The combinatorial assembly of these
genes can yield 1000-2000 biochemically distinct complexes . While often studied as a single complex, these
biochemically distinct forms of SWI/SNF have different functions in gene regulation.Understanding the
mechanisms that regulate SWI/SNF function, and that are therefore disrupted in SWI/SNF mutant tumors, is of
critical importance for developing new therapies.
We propose that post-translational modifications of SWI/SNF and interactions between SWI/SNF and RNA
modulate function of the complex. Understanding how these mechanisms contribute to how different SWI/SNF
complexes are defined is the focus of my lab. The key questions we will address in this project are 1.) Do
variant SWI/SNF complexes have different functions? 2.) What regulates different activities of biochemically
distinct complexes? 3.) How are changes to the composition and the targeting of complexes regulated? Our lab
combines computational, molecular, and biochemical analyses to answer these questions and develop deeper
insight into the mechanisms of SWI/SNF activity. Over the next five years, we will investigate mechanisms that
combine to regulate the composition and function of SWI/SNF and determine how different functional outcomes
are mediated by distinct SWI/SNF complexes. Given the critical role of SWI/SNF in development and disease,
understanding how the complex is regulated to mediate different outcomes is critical for developing new
approaches to targeting cancer and other diseases.

## Key facts

- **NIH application ID:** 10880720
- **Project number:** 5R35GM147286-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Jesse R. Raab
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $388,750
- **Award type:** 5
- **Project period:** 2022-08-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880720

## Citation

> US National Institutes of Health, RePORTER application 10880720, Mechanisms of SWI/SNF complex assembly and function (5R35GM147286-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10880720. Licensed CC0.

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