# Determinants of Cell State Reprogramming

> **NIH NIH R35** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $462,508

## Abstract

Determinants of cell state reprogramming
PROJECT SUMMARY
Forced expression of transcription factors (TFs) can reprogram cell state. The discovery of direct reprogramming
has been a catalyst for our understanding of the molecular and genetic drivers of cell state. However, despite its
successes, only a handful of successful reprogramming cocktails have been identified, the conversion process
is often inefficient, and the mechanistic reasons for reprogramming failure are often unclear. Thus, a key obstacle
to further progress is our incomplete understanding of the determinants and mechanisms of cell state conversion.
Our long term goal is to understand the genetic and molecular basis of cell state, which has important implications
for synthetic control of cell state for regenerative medicine. Towards this goal, the objective of this proposal is to
elucidate the molecular and cellular determinants of cell state reprogramming. Specifically, we seek to address
several fundamental gaps in knowledge on cell state reprogramming with three central research directions: 1)
Epigenetic determinants of cellular reprogramming, 2) Genetic and temporal determinants of cellular
differentiation, and 3) Initial cell state determinants on reprogramming. This scope is made possible by our
innovative platform that couples multifactorial, pooled perturbation with multidimensional readouts for each cell
spanning perturbations (induced TFs), mechanisms (epigenome), and phenotypes (transcriptome). By tracing
thousands of individual cells on their path to reprogramming across a multitude of distinct perturbations, our high
throughput functional experiments will reveal insights and suggest mechanisms for the determinants of
reprogramming. Our rationale is that learning these fundamental rules of reprogramming will improve our
understanding of the molecular basis of cell state and enable improved approaches to manipulate it.

## Key facts

- **NIH application ID:** 10406224
- **Project number:** 1R35GM145235-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Gary Chung Hon
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $462,508
- **Award type:** 1
- **Project period:** 2022-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10406224

## Citation

> US National Institutes of Health, RePORTER application 10406224, Determinants of Cell State Reprogramming (1R35GM145235-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10406224. Licensed CC0.

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