# Comprehensive identification of E3 ubiquitin ligases that degrade heart, lung, and blood-relevant transcription factors

> **NIH NIH F31** · UNIVERSITY OF WASHINGTON · 2024 · $43,808

## Abstract

Project Summary
Faithful development and maintenance of individual cell types in the heart, lungs, and blood (HLB) are
dependent upon cell type-specific decoding of the genome. These cell type-specific transcriptional programs
are the result of the coordinated actions of many transcription factors (TFs), which regulate transcriptional
output in a temporal and locus specific fashion. Due to their central role in HLB biology, a comprehensive
molecular understanding of TF function would reveal the contribution of TFs to maintaining homeostasis, as
well as inform how disruption of this balance can lead to the progression of HLB disorders. While methods to
understand how TFs regulate gene expression exist, we lack methods and analytical tools to assay how TFs
themselves are regulated post-translationally. By narrowly focusing on well-known phenotypes (DNA-binding)
with well-developed methods (CHIP-seq, CUT&Tag), we fail to capture biological information at other
regulatory levels, such as the post-translational control of TF degradation by E3 ubiquitin ligases. Importantly,
this failure is not one of interest, but rather stems from the dearth of facile, scalable methods to study
post-translation regulation of TFs.
To address this critical shortcoming, I will develop a novel assay capable of measuring the effect of genetic
perturbations on TF protein abundance at a scale that is not possible with current methods (Aim 1). I will
initially apply this method to a library of 127 TFs previously demonstrated to have tissue specific expression in
heart, lung, blood, bone marrow, or lymph node 1, and then subsequently scale the method to study the effect of
genetic perturbation on 2000 TFs to comprehensively discover E3 ubiquitin ligases that regulate TF
abundance. (Aim 2). Finally, I will map the minimal peptides necessary for observed changes in protein levels
(Aim 3). This study will provide a target-linked map of E3-TF pairs, and lead to a broader understanding of the
factors controlling transcription factor protein levels. Further, we will gain insights into the role of
post-translational TF regulation in homeostasis as well as the mechanisms by which this homeostasis
becomes dysregulated. Importantly, the E3-TF pairs discovered in this project will be of interest as therapeutic
targets, with each pair representing a novel protein-protein interaction to target for stabilization or ablation.
As a part of the fellowship, I will also undergo a training plan aimed at expanding my abilities as an
experimental biologist as well as improving my knowledge of computational methods and statistics. The
research and training plan will be performed in collaboration with my sponsor and co-sponsor, Dr. Jay
Shendure and Dr. Ning Zheng, both at the University of Washington. My advisors were specifically chosen
because they each have outstanding records of performing cutting edge research and training the next
generation of scientific thought leaders.

## Key facts

- **NIH application ID:** 10874425
- **Project number:** 5F31HL168982-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Chase Cameron Suiter
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $43,808
- **Award type:** 5
- **Project period:** 2023-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10874425

## Citation

> US National Institutes of Health, RePORTER application 10874425, Comprehensive identification of E3 ubiquitin ligases that degrade heart, lung, and blood-relevant transcription factors (5F31HL168982-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10874425. Licensed CC0.

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