# Novel roles for the DNA damage response kinase CHK1 in TCR/ITAM signaling

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $459,342

## Abstract

Project Summary
 The cellular machinery coordinating responses to DNA damage is critically important to ensure that cells
with potentially deleterious defects do not progress through the cell cycle and promote malignant transformation.
To this end, the ATR-activated CHK1 kinase has key functions in the nucleus upon recognition of replication
stress at stalled DNA replication forks by triggering a signaling cascade that halts the cell cycle. However, the
roles for this kinase pair outside the nucleus are less well understood, and a non-canonical function specific to
the immune response has not been explored previously. Using cutting-edge biochemistry, super-resolution
imaging, and cellular and in vivo immunology approaches, two specific aims will be pursued. Aim 1) To define
the molecular connections between CHK1 and T cell receptor (TCR) signaling molecules and their roles in T cell
activation in vivo. Aim 2) To evaluate analogous signaling roles for CHK1 in related receptors of the immune in
order to pinpoint its mechanism of action. These studies are expected to yield fundamental insights into roles
for CHK1, heretofore presumed to function primarily in the nucleus, in cytoplasmic immunoreceptor signaling
events and define the impact of these roles on immunity. The broader implications of these studies include novel
insights into potential effects of ATR and CHK1 inhibitors, currently under evaluation in cancer clinical trials, on
the immune system. These insights may be beneficial in mitigating unexpected effects of these drugs and
maximizing the potential to target ATR/CHK1 or novel downstream mediators therapeutically in diseases of the
immune system.
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## Key facts

- **NIH application ID:** 9966867
- **Project number:** 5R01AI138141-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Carrie L. Lucas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $459,342
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9966867

## Citation

> US National Institutes of Health, RePORTER application 9966867, Novel roles for the DNA damage response kinase CHK1 in TCR/ITAM signaling (5R01AI138141-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9966867. Licensed CC0.

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