Research Summary
Dr. Caron’s laboratory is focused on elucidating unique G protein-coupled receptor pathways that are important for the development and function of the lymphatic vascular system. Using a variety of gene targeted animal models in conjunction with state-of-the-art in vitro cell biological systems, they have discovered fundamental roles for several secretin- and chemokine-family receptors in development and disease. A major area of emphasis is to define the function of adrenomedullin (AM) signaling in lymphatic endothelial cells. Mice with targeted null mutations in AM, or its receptor components CLR and RAMP2, die at mid-gestation with hydrops fetalis associated with proliferative defects in the growth and development of the lymphatic vascular system—a discovery that identifies the first, pharmacologically-tractable GPCR system involved in developmental lymphangiogenesis and confirmed by the recent identification of the first human mutation in CLR associated with hydrops fetalis. The lab has also established a critical role for AM-CLR signaling within lacteals of the small intestine. Mice that lack CLR in lymphatic lacteals fail to gain weight, even under a high-fat diet, and exhibit abnormal accumulation of lipids with lymphatic cells and epithelial cells. Current studies are exploring how CLR signaling can also be exploited by the calcitonin gene-related peptide (CGRP), to regulate sympathetic innervation and control of lacteal permeability and chylomicron absorption. Her interest in the crosstalk between lymphatics and gastrointestinal epithelial cells provides a unique background and interdisciplinary skills to serve as a member of the CGIBD.
CGIBD Focus Area(s): Regeneration and Repair
