# Cross-Testing Genome Integrity Assays in Primary Human Cells

> **NIH NIH U01** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2020 · $145,389

## Abstract

Project Summary/Abstract
This research proposal is focused on cross-validating three complementary genome integrity assays in multiple
types of primary human cells from different individuals. In addition to a repeated measures study with multiple
blood draws from the same individuals over time, we will compare genome integrity assays in multiple types of
blood cells, fibroblasts, and keratinocytes from the same individuals. These samples are from participants in
IRB approved studies supported by the parent projects, and will be shared without identifying information. Each
of the three parent projects involved in this highly synergistic collaborative supplement will benefit from cross-
testing of assays to reveal possible sources of error that may impact a single assay, but are unlikely to impact
all three. Multiple complementary data streams will also enable a more comprehensive understanding the
biological implications of the assay outputs. In particular, the project lead by Dr. Nagel will benefit by having a
second approach, namely a fluorescence based unscheduled DNA synthesis assay that measures repair in the
context of chromatin, and can be directly compared to fluorescence multiplex host cell reactivation (FM-HCR)
assays, particularly those for nucleotide excision repair. The project lead by Dr. Niedernhofer will benefit in a
reciprocal way. The project lead by Dr. Vijg will benefit from the establishment of a platform for using functional
data to distinguish mutations arising from elevated exposure to DNA damaging agents from those arising from
inefficient DNA repair. The projects led by Niedernhofer and Nagel will also both benefit from determining the
extent to which DNA repair deficiencies as detected using functional assays in ex vivo biological samples are
reflected in the number of mutations acquired in tissues from the same individuals in vivo. By determining the
robustness and reproducibility of our assays, and by benchmarking them against other approaches in primary
samples from human subjects with defined defects in the NER pathway, this supplement also advances the
overall objective of the consortium, namely to facilitate the wider use of genome integrity assays in human
populations.

## Key facts

- **NIH application ID:** 10139218
- **Project number:** 3U01ES029520-03S1
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** David C Christiani
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $145,389
- **Award type:** 3
- **Project period:** 2018-09-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10139218

## Citation

> US National Institutes of Health, RePORTER application 10139218, Cross-Testing Genome Integrity Assays in Primary Human Cells (3U01ES029520-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10139218. Licensed CC0.

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