# New regulators of natural killer cell-mediated cytotoxicity

> **NIH NIH R03** · UNIVERSITY OF COLORADO DENVER · 2021 · $77,750

## Abstract

PROJECT SUMMARY
Natural killer (NK) cells are key effector lymphocytes in the innate immune system. They exhibit the
remarkable abilities of detecting and eradicating transformed and virus-infected cells. NK cells also play a key
role in the rejection of transplanted organs from allogeneic donors. Imbalances in NK cell-mediated killing are
associated with major forms of human disease such as cancer, chronic infection, and immunodeficiency. To
improve the efficacy of NK cell-based therapies, it is critical to identify the genes controlling the response of
target cells to NK cell-mediated killing. In our preliminary studies, we performed genome-wide genetic screens
to dissect target cell killing by an NK-like cell line. The screens isolated known regulators of NK cell killing but
the majority of the hits were not previously linked to NK cell functions. The major goal of this pilot project is to
validate and characterize these candidate genes using human primary NK cells. Each of these genes will be
individually deleted in target cells using CRISPR genome editing. We will then determine how the knockout
cells respond to killing by primary NK cells. Once a candidate gene is validated, we will further characterize
its function and mechanism in NK cell-mediated cytotoxicity. Successful completion of this pilot project will
substantially broaden our knowledge of how NK cells recognize and kill target cells. Insights gleaned from
this work will help improve the efficacy and safety of immunotherapies for cancer and pathogen infection.

## Key facts

- **NIH application ID:** 10110784
- **Project number:** 1R03AI156560-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Suzhao Li
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $77,750
- **Award type:** 1
- **Project period:** 2021-03-11 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10110784

## Citation

> US National Institutes of Health, RePORTER application 10110784, New regulators of natural killer cell-mediated cytotoxicity (1R03AI156560-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10110784. Licensed CC0.

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