# Project 1 Rabadan

> **NIH NIH P01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $341,519

## Abstract

PROJECT SUMMARY/ABSTRACT:
Large-scale genomic studies of human tumors have uncovered a series of characteristic “mutation signatures”;
i.e., statistically enriched patterns of DNA substitutions and rearrangements common across tumors. While
some of these signatures are associated with particular cancer subtypes, known genotoxic insults, and/or
rough mutational patterns arising from specific DNA repair defects, most remain uncharacterized without
known biological correlates. To determine the mechanisms by which mutation signatures arise, we will initially
focus on triple-negative breast cancers (TNBCs) with lesions in the BRCA1 tumor suppressor pathway. Recent
studies have identified at least five distinct mutation signatures in TNBCs. However, we do not know if
additional signatures exist, nor do we understand the molecular mechanisms by which these signatures are
generated. BRCA1 acts to preserve genome integrity through multiple processes, including homology-directed
repair (HDR) and stalled fork protection (SFP), and it does so in association with a number of distinct protein
partners. Thus, the mutation signatures associated with TNBC may reflect the loss of particular BRCA1
pathway functions and/or defects in other as yet unidentified DNA repair factors. To address these issues, we
will combine expertise in computation analysis of genomic data and the molecular biology of DNA repair to 1)
elucidate the molecular mechanisms responsible for TNBC mutation signatures, and 2) determine the full
spectrum of mutation signatures associated with TNBC patients bearing pathogenic lesions in the BRCA1
pathway.

## Key facts

- **NIH application ID:** 10819476
- **Project number:** 5P01CA174653-10
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Raul Rabadan
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $341,519
- **Award type:** 5
- **Project period:** 2014-04-08 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10819476

## Citation

> US National Institutes of Health, RePORTER application 10819476, Project 1 Rabadan (5P01CA174653-10). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10819476. Licensed CC0.

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