# Davoli/Mita Diversity Supplement

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $124,979

## Abstract

Summary of the funded parent grant
Our cells are constantly exposed to (endogenous and exogenous) mutagens that cause DNA damage, which if
left unrepaired, causes mutations. At the cellular level, the progressive accumulation of mutations in somatic
tissues drives carcinogenesis and other diseases. Despite our large body of knowledge of DNA damage and
repair in model organisms, we lack a deep understanding of this process in human tissues. What are the genetic
causes of mutations in human tissues? How do different cell types control DNA damage and repair?
Answering these questions is critical to understand how mutations lead to human diseases, such as
carcinogenesis.
Here we will use a highly innovative approach to build MutSensor, a set of mutation reporters to estimate
DNA mutation frequency in mammalian cells with a sensitivity >50-fold higher than that of existing
methods. The ability to build and precisely deliver these MutSensors is enabled by “Genetic Writing and Delivery”
method developed in the Boeke lab. This novel method will allow functional genetic screening at an
unprecedented scale. Building on our preliminary data, we aim at comprehensively identify all genes that regulate
mutation frequency in different human cell types, including cancer cell lines. To this purpose, we will utilize loss-
and gain-of-function approaches (from the Davoli lab) to determine the effect of genetic perturbations on mutation
frequency in human cells.
These studies will provide an unprecedented map of genes controlling DNA damage and mutations in different
human cell types. In addition, our novel method will represent an important asset for the scientific community
providing an easy way to study genetic and environmental factors that control mutagenesis in health
and disease states, including carcinogenesis.

## Key facts

- **NIH application ID:** 11090156
- **Project number:** 3R01HG012590-02S1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Jef D BOEKE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $124,979
- **Award type:** 3
- **Project period:** 2023-09-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11090156

## Citation

> US National Institutes of Health, RePORTER application 11090156, Davoli/Mita Diversity Supplement (3R01HG012590-02S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/11090156. Licensed CC0.

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