# Measuring genomic DNA damage and DNA repair capacity in longitudinal population samples - a step towards precision prevention

> **NIH NIH U01** · UNIVERSITY OF SOUTH ALABAMA · 2021 · $549,244

## Abstract

Project Summary
Advanced technologies for characterizing human populations at the molecular level have set the stage for
personalized therapeutic strategies that may also provide an opportunity for personalized prevention.
Personalized or ‘Precision Prevention’ would therefore provide an opportunity to identify those at high risk for a
given disease, in part based on defined functional defects (such as a defect in genome maintenance), so as to
advise for targeted screening and primary prevention interventions early in life to alter disease susceptibility. DNA
repair pathways maintain the integrity of the genome and thereby help prevent the onset of cancer, disease and
aging phenotypes and play a significant role in the cellular and organismal response to environmental exposures.
In the vein of precision prevention, identifying those with functional defects in the maintenance of genome integrity
would be a first step as such ‘carriers’ would have an increased risk of exposure-associated pathologies. Many of
these cancer- or disease-specific DNA repair defects can be detected using current "omics" technologies such as
evaluating changes in mRNA expression, alterations in the DNA coding sequence or modulations in cellular
metabolites such as NAD+ metabolites known to regulate mitochondrial function and regulate DNA repair
pathways, as we have shown. However, there are many defects that can only be detected from a direct analysis
of basal genome integrity and a direct measure of the cellular capacity to repair the genome in response to
exogenous genotoxins. In response to RFA-ES-17-006: Expanding Genome Integrity Assays to Population
Studies, we propose Aims that will advance our capacity to examine human populations for genome damage and
genome repair capacity, illuminating variations between individuals at discrete time-points as well as within
individuals across a five-year period. Genome integrity and DNA repair capacity in sentinel PBMCs at basal level
and following challenge by environmental genotoxins will be evaluated using a newly developed next-generation
high-throughput DNA damage detection platform. The advances of this new platform have now opened the door
for the analysis of large-scale population cohorts, providing a huge step forward in human biomonitoring
opportunities. These studies will provide the first look at a longitudinal measure of genome integrity in a
community-based cohort of mostly African American descent and will advance our capacity to interrogate human
populations for genome damage and genome repair capacity.

## Key facts

- **NIH application ID:** 10202602
- **Project number:** 5U01ES029518-04
- **Recipient organization:** UNIVERSITY OF SOUTH ALABAMA
- **Principal Investigator:** Robert W Sobol
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $549,244
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10202602

## Citation

> US National Institutes of Health, RePORTER application 10202602, Measuring genomic DNA damage and DNA repair capacity in longitudinal population samples - a step towards precision prevention (5U01ES029518-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10202602. Licensed CC0.

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