Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Lymphatic primary cilia regulation of intercellular junctions and valve formation

Award Number: R01HL175395
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/20/2026
PERIOD OF PERFORMANCE END DATE: 01/31/2031

Group Awards By:

View Award Description

Lymphatic primary cilia regulation of intercellular junctions and valve formation - Lymphatic valve dysfunction disrupts lymph transport, causing lymphedema – a condition characterized by irreversible tissue fibrosis and increased infection risk due to impaired immunosurveillance. Current standard of care manual lymph drainage and compression therapy fail to target the underlying molecular defects. This NIH R01 proposal builds on our discovery of the intraflagellar transport (IFT) system in lymphatic endothelial cells (LECs), focusing on IFT74 and IFT20 as critical regulators of lymphatic valve morphogenesis. IFT proteins, such as IFT74, are required for the assembly and maintenance of primary cilia, cell surface chemo- /mechanosignaling organelles that we recently discovered on LECs. IFT20 also performs essential non-ciliary processes, including trafficking adhesion and extracellular matrix (ECM) proteins. Our central hypothesis is that IFT proteins assemble primary cilia to promote shear stress-dependent lymphatic valve initiation and support valve maturation by non-ciliary trafficking of ECM and adhesion proteins to the cell surface to reinforce valve leaflets. Our preliminary data reveal that LEC-specific IFT74 knockout (KO) mice suffer defects in valve formation, while IFT20 KO mice show excessive lymphangiogenesis and impaired VE-cadherin recycling with more modest valve maturation defects, highlighting their distinct contributions. Specific Aim 1 will determine how IFT74/primary cilia enable lymphatic endothelial cells (LECs) to sense shear stress and initiate valve development. We will investigate ciliary signaling pathways using in vitro calcium flux assays, the role of transcriptional de-repression in valve morphogenesis, and identify valve-specific gene networks controlled by primary cilia via spatial transcriptomics. Specific Aim 2 will investigate how non-ciliary IFT20 regulates valve maturation by coordinating VE-cadherin recycling, integrin adhesion, and ECM deposition to stabilize valve leaflets. To determine how non-ciliary IFT20 exocytic trafficking promotes valve maturation, we will use intravital microscopy with transgenic reporters and second harmonic generation to observe valve formation and junctional/ECM dynamics in real time. We aim to elucidate the mechanisms of valve initiation and maturation, positioning IFT74/primary cilia and IFT20 and their downstream effectors as potential therapeutic targets for lymphedema. By connecting ciliary mechanosensation to valve development and non-ciliary trafficking to valve stability, we will build a comprehensive molecular model of IFT regulation of valve morphogenesis. Aligned with the NIH NOSI on the lymphatic system, this research seeks to enhance lymphatic transport capacity and guide the development of new therapies for lymphatic disorders.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $452,869 )
2026	2026	SOUTH DAKOTA STATE UNIVERSITY	1015 CAMPANILE AVENUE	BROOKINGS	SD	57007	BROOKINGS	USA	Cardiovascular Diseases Research	000	1	4/24/2026	NEW	$452,869
														Subtotal = $452,869

Grand Total All Awards = $452,869

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Lymphatic primary cilia regulation of intercellular junctions and valve formation

Award Number: R01HL175395

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/20/2026

PERIOD OF PERFORMANCE END DATE: 01/31/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer