The role of apelin receptor signaling in lymphatic vessel
openNHLBI - National Heart Lung and Blood Institute
Project Summary:
Mechanical forces, including extrinsic compression from surrounding tissues and intrinsic pressures such
as wall shear stress (WSS), are critical for normal lymphatic functions, which are essential in maintaining fluid
homeostasis, trafficking immune cells, and absorbing intestinal lipids. Dysfunction of lymphatic vessels can lead
to disabling and sometimes life-threatening tissue swelling known as lymphedema (LD). An estimated 250 million
individuals worldwide suffer from LD, yet no effective treatments are currently available. Apelin, through activation
of its receptor, Apelin Receptor (APJ, gene APLNR), is an emerging effective treatment for LD in humans. APJ
can be activated by ligands, Apelin and Elabela (ELA), and by mechanical forces. APJ signaling is critical in
regulating lymphatic functions such as lymphatic vessel development, vasodilation, and restores lymphatic
function, but the precise coordination of receptor ligand-mediated signaling and mechanotransduction to govern
the protective effects of APJ remain unclear. Therefore, my central hypothesis is that integrated APJ signaling—
activated by both ligands and mechanical forces—is critical for maintaining the normal physiological function of
lymphatic vessels. Results from my studies will provide mechanistic characterization of APJ signaling in the
lymphatic system, laying the foundation for its therapeutic potential in LD, including ongoing clinical trials. The
training opportunities in this proposal have expansive translational value for the treatment of LD and will facilitate
successful transition of Dr. Yanna Tian’s career from a postdoctoral fellow to an independent researcher. Dr.
Kathleen M. Caron, a world-renowned scientist specializing in GPCR signal transduction and lymphatic vessel
biology, will support this proposal and mentor Dr. Tian’s scientific and career development, facilitating her
transition to independence throughout this award. To enhance training, Dr. Caron and Dr. Tian have established
an advisory mentoring team, comprising Drs. Dixon, Polacheck, and Kim, and external consultant, Dr. Garmy-
Susini, who will provide expertise across all relevant areas of this proposal. The supportive research environment,
with the NIH Pathway to Independence Award (K99/R00), will facilitate a successful transition of Dr. Tian’s career
to a competitive and independent tenure-track research position.
Up to $110K
health research