# Elucidating the GPCR protein networks that drive lymphatic growth

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $40,759

## Abstract

Project Summary/ Abstract: Lymphatic diseases are numerous and affects upwards of 200 million people
worldwide. These chronic disorders have limited clinical management and are broadly characterized by aberrant
lymphatic vessel development and/or dysfunction which results in painful accumulation of interstitial fluid.
Shockingly, no FDA-approved pharmacological treatments targeting lymphangiogenesis, the process of
lymphatic vessel formation, are available. Thus, there is an urgent need to characterize key therapeutically
tractable proteins and signaling pathways that regulate lymphangiogenesis. The Caron laboratory studies one
such molecule, the potent pro-lymphangiogenic peptide, adrenomedullin (AM). AM-induced lymphangiogenesis
requires formation of well-controlled AM-chemotactic gradients to provide directionality to growing and migrating
lymphatic vessel tips. The atypical chemokine receptor 3 (ACKR3) is critical for the establishment of these
gradients through the internalization and degradation of AM. Recently, the Caron laboratory identified a novel
interaction between ACKR3 and receptor-activity-modifying protein 3 (RAMP3). They showed in vitro that
RAMP3 is required for the recycling of ACKR3 to the plasma membrane after AM-stimulated internalization and
that loss of ACKR3 or RAMP3 in vivo results in impaired vascular development. However, the mechanism by
which RAMP3 regulates ACKR3 activity and signaling in lymphatic endothelial cells (LECs) and the process of
lymphangiogenesis remains unknown. RAMP3 is unique among the RAMPs in that it contains a C-terminal PDZ
motif that mediates its function by promoting protein-protein interactions with PDZ domain-containing proteins.
Therefore, the overarching hypothesis of this training proposal is that RAMP3 and its PDZ motif enhances
ACKR3 activity and signaling within LECs to regulate lymphangiogenesis. Completion of this proposal will define
the role of RAMP3 in the regulation of ACKR3 signaling and lymphangiogenesis, thereby advancing the current
knowledge of the lymphatic biology field. In addition, this proposal will provide invaluable experience and training
in the performance of ethical and rigorous research and effective scientific communication.

## Key facts

- **NIH application ID:** 10462115
- **Project number:** 1F31HL163885-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Donald Stephen Serafin
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $40,759
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10462115

## Citation

> US National Institutes of Health, RePORTER application 10462115, Elucidating the GPCR protein networks that drive lymphatic growth (1F31HL163885-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10462115. Licensed CC0.

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