# Epigenesis of Cell Fate Potential

> **NIH NIH R35** · UNIVERSITY OF CHICAGO · 2020 · $399,048

## Abstract

PROJECT SUMMARY/ABSTRACT
The coordination of cellular function to developmental and environmental cues is essential for organismal
growth and adaptation. Cells have a remarkable ability to sense diverse stimuli and make regulatory decisions
to elicit an appropriate response. Our laboratory is interested in the molecular underpinnings of this cellular
decision-making. Seminal “receptor-switch” experiments demonstrated that the cell’s sensing apparatus does
not alone promote a specific cell fate. Rather, the cell’s sensing mechanism triggers a pre-existing nuclear
program that was poised during development. How is this pre-existing program established? At what stage in
development does it occur? What are the determinants that establish and maintain this potential for lineage-
specific effector responses? The long-term goal of the laboratory is to define the biological processes that
provide answers to these fundamental questions. Our model system is T cells, an ideal framework because
the stages of development are highly characterized and the cells are widely available. Our approach focuses
on the regulation of chromatin, i.e. the 6 billion bases of human DNA wrapped around nucleosomes that can
take on different conformations to define gene activity and cellular identity. One of the modes by which
chromatin is regulated is through the actions of chromatin remodeling complexes that use energy from ATP to
modify which regions of the genome are accessible to transcription factors and signaling pathways. We have
recently identified a novel chromatin remodeling complex that promotes the accessibility of genes encoding
specialized T cell function. This ATPase motor acts early in development to poise cells even prior to the
expression of the T cell receptor. In the next 5 years, we aim to identify the subunit composition of this novel
chromatin remodeling complex and the direct mechanistic modes that mediate complex targeting and function
at T cell effector loci. Achievement of our research goals will also provide a foundation for advances in clinical
applications of T cell biology, e.g modulation of T cell effector programming to enhance the efficacy of
vaccination, cancer immunotherapy, or tolerance induction for autoimmunity.

## Key facts

- **NIH application ID:** 10029167
- **Project number:** 1R35GM138150-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Andrew S Koh
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $399,048
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10029167

## Citation

> US National Institutes of Health, RePORTER application 10029167, Epigenesis of Cell Fate Potential (1R35GM138150-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10029167. Licensed CC0.

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