Cellular context of ramp-gpcr signaling in lymphatic microvasculature
Active Project Grant Awarded Last action
- Award ID
- F31HL186613
- Recipient
-
University Of North Carolina At Chapel Hill UEI D3LHU66KBLD5 Part of University Of North Carolina System Office
- Awarding agency
-
National Heart Lung and Blood Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $82,680
Award facts
- Assistance listing
- 93.837 Cardiovascular Diseases Research
- Completion date 0% complete
- Originally
- Place of performance
- Chapel Hill, NC 27599, USA
Award details come from USAspending.gov.
Description
- Abstract
- The lymphatic system is a network of vessels that helps maintain the homeostasis of interstitial fluid volume and supports immune responses in the periphery. There is an increasing appreciation for the importance of these functions because impaired lymphatic drainage has been implicated in multiple pathologies including neurodegenerative, metabolic, cardiovascular, autoimmune, and inflammatory diseases. Further, one of the most common lymphatic disorders, lymphedema, has been estimated to affect approximately 200 million people worldwide and 10 million americans. Despite its high prevalence, there is no FDA-approved pharmacological treatment for lymphedema. Therefore, further study of lymphatic biology will provide foundational knowledge for the improvement of lymphatic vascular function in both lymphatic-specific and lymphatic-associated conditions. One pathway that warrants further investigation is mediated by calcitonin gene-related peptide (CGRP). This peptide acts on its canonical receptor which is a heterodimer of the G-protein coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) and its allosteric regulator receptor activity-modifying protein 1 (RAMP1). Our lab was the first to show that CGRP activates creb, ERK, and AKT signaling in lymphatic endothelial cells and that these pathways functionally result in the formation of continuous, nonpermeable cell junctions in vitro and in vivo. Other research groups have demonstrated that global loss of RAMP1 in a homozygous knockout mouse model results in lymphedema phenotypes and decreased lymphatic vessel growth. However, we do not fully understand the implications of these studies because of the widespread expression of CGRP receptors in numerous cell types and the complex signaling patterns of CGRP mediated by ramps. To fully elucidate the effects of CGRP signaling in the lymphatic vasculature, we need a better understanding of the different factors that regulate its context-specific signaling. In this proposal, I aim to define lymphatic endothelium-specific CGRP-RAMP1 signaling and interrogate how external factors influence the activation of downstream signaling pathways using cutting-edge proteomic techniques, innovative biosensor platforms, and novel genetically engineered mouse models.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $41,340 | |
| Amendment | $41,340 | |
| Original award | $0 |
Quick answers
Who received award F31HL186613?
F31HL186613 was awarded to University Of North Carolina At Chapel Hill by National Heart Lung and Blood Institute (National Institutes of Health) on December 15, 2026.
How much is award F31HL186613 worth?
$82,680 has been obligated on F31HL186613.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award