# Reducing Cancer Transcriptional Heterogeneity through Regulation of Chromatin Structure

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $607,121

## Abstract

PROJECT SUMMARY
Carcinogenesis involves the dysregulation, both mutational and transcriptional, of the complex interactions
of hundreds of genes. Currently no platform allows for the predictable transcriptional modulation of this many
genes simultaneously. Gene transcription is modulated by a number of mechanisms including the well-studied
histone modification and genome compartmentalization mechanisms as well as the still insufficiently
understood role of the complex physical nanoenvironment within chromatin. Since transcriptional molecular
interactions are chemical reactions, they depend on the local physical environment within the chromatin
which, in turn, depends on the physical pattern of chromatin folding at supra-nucleosomal length scales. The
overarching goal of this project is to develop new tools to modulate the chromatin nanoenvironment for whole-
scale transcriptional engineering for cancer prevention and therapeutics. Transcriptional diversity plays a
major role in carcinogenesis by allowing cancer cells to explore their genomic space and has been shown to
foster the emergence of resistance to chemotherapy in cancer cells. The project will leverage the methods of
bioengineering to develop new tools to physico-chemically regulate chromatin structure toward a normalized,
constrained, and less-adaptive state. The project will identify physico-chemical mechanisms that can be targeted
to reduce transcriptional heterogeneity and validate the efficacy of the chromatin folding-normalization in patient-
derived xenograft (PDX) tumor models of colon cancer as an adjuvant therapy for alleviating chemoresistance
through the reduction of the transcriptional heterogeneity of tumors.

## Key facts

- **NIH application ID:** 10376877
- **Project number:** 5R01CA228272-05
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Vadim Backman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $607,121
- **Award type:** 5
- **Project period:** 2018-04-09 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10376877

## Citation

> US National Institutes of Health, RePORTER application 10376877, Reducing Cancer Transcriptional Heterogeneity through Regulation of Chromatin Structure (5R01CA228272-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10376877. Licensed CC0.

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