# Signaling circuits that drive cell movement and ligand scavenging by chemokine receptor CCR2

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $27,361

## Abstract

Abstract
Monocyte migration into tissues, guided by inflammatory chemokine CCL2 and its G protein-coupled receptor
CCR2, is key to normal physiology and to the pathology of numerous diseases including neurodegeneration,
traumatic brain injury, arthritis, diabetic nephropathy, and non-alcoholic fatty liver disease. However, despite its
therapeutic significance, the role of CCR2 in monocyte function is still poorly understood. In addition to its well-
recognized ability to promote cell movement, CCR2 possesses a different, equally important but largely
unappreciated function: it scavenges and removes chemokines from the extracellular medium. Scavenging may
enable CCR2-expressing cells to move along gradients of increasing chemokine concentration without
desensitizing; it may also mediate intercellular coordination and crosstalk by altering the availability of CCL2 and
other chemokines to their receptors on different cells.
The present application is a supplement to R01 GM136202 titled “Signaling circuits that drive cell movement and
ligand scavenging by chemokine receptor CCR2,” and awarded to PIs Handel and Kufareva for the period of
2020-24. The objective of the parent proposal is to achieve a comprehensive and predictive systems-based
understanding of CCR2 migration and scavenging functions. The experimental and computational advances that
the applicants made on all three Aims of the parent R01 during its first year revealed the need for better,
systematic and quantitative platforms for computational modeling of CCR2 trafficking, interactome, and phospho-
signaling. Many of these findings materialized as a result of the work of a talented Hispanic undergraduate
student, Alexis Lona, who is currently a part-time volunteer intern in the Kufareva lab but seeks a more extensive
and structured training/engagement. This supplement will enable Alexis to best address the growing
computational needs of the parent R01 while at the same time enhancing his research capability and ultimately
helping him achieve his long-term career goal of becoming a medical scientist.
The applicant will pursue two scientific Aims, both related to Aims 2 and 3 of the parent R01. In Aim S1, he will
build a framework for in silico agent-based modeling of CCR2 trafficking and interactions and for model
calibration against unbiased proximity biotinylation data. In Aim S2, the trainee will develop a methodology for
the modeling of phospho-signal propagation downstream of CCR2 from multifactorial time-resolved
phosphoproteomics data. The scientific Aims are complemented by a comprehensive training and mentoring
plan designed to structure and facilitate the research and career development of the candidate.
As a Hispanic student, Alexis will promote diversity in science by being part of a research lab, and medicine by
becoming a medical scientist and professional. With proper education and training, Alexis will be able to further
science as a service to others while simultaneously p...

## Key facts

- **NIH application ID:** 10488001
- **Project number:** 3R01GM136202-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Tracy M Handel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $27,361
- **Award type:** 3
- **Project period:** 2020-05-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10488001

## Citation

> US National Institutes of Health, RePORTER application 10488001, Signaling circuits that drive cell movement and ligand scavenging by chemokine receptor CCR2 (3R01GM136202-03S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10488001. Licensed CC0.

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