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Illuminating Orphan GPCRs in Lymphatics

阐明淋巴管中的孤儿 GPCR

基本信息

批准号：
10216726
负责人：
Kathleen M Caron
金额：
$ 15.55万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10216726
关键词：
Accounting Adult American Animal Model Animals Area Arrestins Bioinformatics Biology Categories Cells Clinical Coupling Cultured Cells Data Development Drug Targeting Dysplasia Embryo FAIRE sequencing Fatty acid glycerol esters Funding Future G-Protein-Coupled Receptors GTP-Binding Proteins Genes Genetic Genetic Engineering Genome Goals Growth Human Human Development Human Genome Hydrops Fetalis Immune In Vitro Individual Intercellular Fluid Knockout Mice Knowledge Laboratories Learning Ligands Liquid substance Lymph Lymphangiogenesis Lymphatic Lymphatic Diseases Lymphatic Endothelial Cells Lymphatic function Lymphedema Manuals Massage Medicine Methods Mission Modeling Modern Medicine Molecular Chaperones Molecular Target Mus Orphan Pathway interactions Pharmacology Phenotype Physiological Protein Family Proteins Regulation Reporter Research Research Proposals Role Series Source Study models System Technology Testing Therapeutic Agents United States National Institutes of Health absorption adrenomedullin base calcitonin receptor-like receptor compression therapy human disease in vivo interest loss of function mutation lymphatic vasculature lymphatic vessel new therapeutic target novel receptor recruit response spatiotemporal therapeutic target tool trafficking vascular bed

项目摘要

ABSTRACT Since more than 40% of all clinically-available drugs target G-protein coupled receptors (GPCRs), there is great interest in learning more about this family of proteins in order to discover new therapeutic targets. When considering the different classes of proteins encoded by the human genome that are predicted to be pharmacologically-tractable, a remarkable one quarter represent GPCRs. And yet, of the ~345 non-odorant GPCRs a large proportion remain orphan—with no known ligand—or have uncharacterized physiological functions. Since we have a dearth of pharmacological targets for lymphatic vessels, it stands to reason that focused efforts to explore and characterize the lymphatic “GPCRome” is a worthwhile endeavor. We have identified 3 orphan GPCRs that are IDG-eligible target proteins in the Illuminating the Druggable Genome (IDG) Project. We propose to develop and use in vitro and animal-based systems to further characterize the expression and activation of these GPCRs in the lymphatic vasculature. Our results will further the overall goals of the IDG Consortium and reveal novel physiological pathways and potential therapeutic targets for the modulation of lymphatics, which remains an understudied research area with unmet clinical needs.

摘要