# Genome Instability Induced Anti-Tumor Immune Responses

> **NIH NIH P01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $1,625,041

## Abstract

Summary
The overarching objective of this Program Project Grant is to understand fundamental
mechanisms underlying communication between cancer cell genomic instability and the immune
system. Foundational work from the investigators on this P01 demonstrates multivariate ways in
which genomic damage is aberrantly detected as “foreign” by pattern recognition receptors that
are typically used to sense viral nucleic acids. The collective body of work from our groups
establish that DNA damage, changes in tissue architecture, mitotic errors, and nuclear envelope
fragility serve to breach cell intrinsic barriers that prevent endogenous DNA and RNA from
detection by innate immune pattern recognition sensors. These events critically affect the tumor
microenvironment to either promote or suppress tumor growth. To achieve our goals, we have
assembled three Projects that will work closely with three Cores to address critical questions on
detection of genome instability in tumors by the immune response. Project 1 investigates the
relationship between DNA damage responses and pattern recognition of endogenous DNA and
RNA in the cytoplasm. Project 2 tests hypotheses on how disruption in tissue architecture and
mechanical forces result in chromosome missegregation and instability. It describes an approach
to understand innate immune system recognition of this instability. Project 3 investigates in vivo
responses to DNA damage within tumors, while designing rational approaches to enhance anti-
tumor immune activation. Integration of these multidisciplinary projects with Mammalian Artificial
Chromosome and Chemical Biology Cores will advance our primary goal of defining the molecular
basis for immune detection of genome instability in cancer.

## Key facts

- **NIH application ID:** 10838530
- **Project number:** 5P01CA265794-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Roger A Greenberg
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,625,041
- **Award type:** 5
- **Project period:** 2023-05-08 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10838530

## Citation

> US National Institutes of Health, RePORTER application 10838530, Genome Instability Induced Anti-Tumor Immune Responses (5P01CA265794-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10838530. Licensed CC0.

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