# Stiff, solid microenvironments induce Chromosome loss and challenge Epigenetic therapies

> **NIH NIH U01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $116,406

## Abstract

ABSTRACT:
This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-
CA-24-029. Our proposed projectfacilitates a new collaboration and introduces Asst Professor Karmella Haynes
as a newInvestigator to NCI and its PSON Program. Our parent award U01-CA254886 has begun yr-4 and
focuses on solid tumors and genetic instability through development of novel fluorescent `ChReporters'. These
enable us to image and track the first induction of chromosome loss and propagation into colonies. This is
expected to decrease the levels of Tumor Suppressors (e.g. p53, PTEN, APC, etc.), which is understudied in
these contexts and is the focus of our efforts. The Haynes lab brings deep expertise in epigenetics including
regulation of Tumor Suppressor genes, which are a major challenge in cancer, because loss of these key factors
is a major modern challenge to rescue (and lagging behind successes in inhibition of Oncogenes). Solid tumors
exhibit more chromosome losses and gains than liquid tumors, and clinical efforts with epigenetic drugs that
possibly rescue Tumor Suppressor levels to some extent are showing better efficacy in Liquid tumors. All of this
motivates our studies of chromosome loss using our ChReporters in Solid Tumor models to address how such
drugs as well as molecularly specific CRISPR approaches affect Tumor Suppressor levels and cancer-related
phenotypes.

## Key facts

- **NIH application ID:** 11074292
- **Project number:** 3U01CA254886-04S2
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Dennis E. Discher
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $116,406
- **Award type:** 3
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11074292

## Citation

> US National Institutes of Health, RePORTER application 11074292, Stiff, solid microenvironments induce Chromosome loss and challenge Epigenetic therapies (3U01CA254886-04S2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11074292. Licensed CC0.

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