# Role of EGFR in signaling by receptors of intracellular nucleic acids

> **NIH NIH P01** · CLEVELAND CLINIC LERNER COM-CWRU · 2020 · $415,847

## Abstract

PROJECT 1: PROJECT SUMMARY 
Production of inflammatory cytokines and interferons by innate immune cells, within the tumor 
microenvironment, is a major determinant of tumor progression. Damage-associated molecular pattern 
(DAMP) recognizing receptors in myeloid cells are activated by ligands generated by the tumor cells, cytokines 
are induced locally and act upon the tumor cells to promote or impair their proliferation. Recent literature 
suggests that DNA and RNA are the major mediators of communication between the tumor cells and the innate 
immune cells. Our interests are in analyzing the biochemical pathways of signaling elicited by specific nucleic 
acid receptors in myeloid cells and investigating the effects of their manipulations in mouse models, which will 
be greatly facilitated by the newly generated TLR3, TLR9 and EGFR conditional knock-out mouse lines. We 
will test the hypothesis that the protein tyrosine kinase (PTK) activity of the epidermal growth factor receptor 
(EGFR) is essential for signaling by the two endosomal Toll-like receptors, TLR3 and TLR9, and by STING, the 
ER-bound mediator of cytoplasmic DNA signaling. Specifically, we will investigate the roles of EGFR and Src in 
TLR3 and TLR9 signaling by determining the biochemical requirements for TLR, EGFR and Src interactions to 
elicit signals. We will also identify the specific functions of EGFR and the adaptor protein, TRIF, in mediating 
STING-signaling and their contributions to STING-mediated protection from viral pathogenesis in mice will be 
evaluated. Finally, we will evaluate the role of EGFR-mediated cytokine production by myeloid cells in 
regulating tumor growth in three murine model systems: chemically induced skin and colon cancers and 
transplanted glioma. The above studies will illuminate the different mechanisms by which EGFR promotes 
signaling by three intracellular nucleic acid DAMP- recognizing receptors and thereby affects tumor growth.

## Key facts

- **NIH application ID:** 9891019
- **Project number:** 5P01CA062220-25
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** GANES C. SEN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $415,847
- **Award type:** 5
- **Project period:** — → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891019

## Citation

> US National Institutes of Health, RePORTER application 9891019, Role of EGFR in signaling by receptors of intracellular nucleic acids (5P01CA062220-25). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9891019. Licensed CC0.

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