# Regulation of chemokine receptor signaling

> **NIH NIH R35** · MEDICAL COLLEGE OF WISCONSIN · 2024 · $507,000

## Abstract

PROJECT SUMMARY
G protein-coupled receptor (GPCR) signaling plays an essential role in many physiological processes and is also
involved in many human diseases, yet the mechanisms governing GPCR signaling remain poorly understood.
The goal of the proposed research is to further our mechanistic understanding of GPCR signaling. The model
GPCR receptor we study is the therapeutically relevant C-X-C chemokine receptor 4 (CXCR4). CXCR4 signaling
is important for embryogenesis, immune function and stem cell regulation, among other functions. In addition,
CXCR4 signaling is involved in several human diseases, including cancer. CXCR4 is aberrantly expressed in
many cancers and its expression correlates with poor prognosis. This is mainly because CXCR4 signaling
contributes to metastatic disease, the reason for most cancer related deaths. Yet the mechanisms governing
CXCR4 signaling remain poorly understood. To achieve our goal, we will address two main questions: 1. What
are the biophysical and structural determinants driving GPCR signaling by β-arrestins via non-GPCR binding
partners? 2. What are the roles of PKCd and A-kinase anchoring proteins (AKAPs) in compartmentalized
heterologous regulation of GPCR signaling? To address these questions, we will mainly use cell culture models
and reconstitution assays using several complimentary integrative approaches including biophysical,
biochemical, proximity ligation, multi-labeling fluorescence confocal microscopy, live cell imaging, and signaling
assays. We believe our research is significant because we expect to define new concepts that apply broadly
across the GPCR family, which will provide an advanced explanation of the mechanisms driving GPCR signaling.
Our research hold the promise to translate new knowledge into innovative drug discovery efforts to modulate
GPCR signaling therapeutically.

## Key facts

- **NIH application ID:** 10912434
- **Project number:** 5R35GM149253-02
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Adriano Marchese
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $507,000
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912434

## Citation

> US National Institutes of Health, RePORTER application 10912434, Regulation of chemokine receptor signaling (5R35GM149253-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10912434. Licensed CC0.

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