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

Contribution of Endothelial Planar Cell Polarity pathways in Blood Flow Direction Sensing

Award Number: F31HL168920
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/01/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2026

Group Awards By:

View Award Description

Contribution of Endothelial Planar Cell Polarity pathways in Blood Flow Direction Sensing - PROJECT SUMMARY Vascular function and development are largely mediated by vascular endothelial cells (VECs) that line the inner wall of blood vessels. Fluid shear stress (FSS) generated by blood flow is a major determinant of their function and phenotype with major roles in development, physiology, and disease. VECs in healthy regions of arteries are under unidirectional laminar flow, where they align in the direction of flow and activate anti-inflammatory pathways which confers resistance to atherosclerosis. By contrast, VECs in curved or branched regions of arteries develop disturbances in flow patterns. These disturbed flow patterns fail to align VECs and activate inflammatory pathways, which correlates with susceptibility to form atherosclerotic plaque. FSS direction with respect to cell alignment also regulates inflammatory signaling outputs, which suggests cell polarity and flow direction sensing is important for the differential atheroprotective and atheroprone responses. Thus, how VECs sense and respond to flow direction is an important basic science question pertinent to human health, but the mechanism is unclear. A junctional flow-dependent complex comprising of VE-Cahderin, PECAM1, and VEGF is critical for integrating endothelial cell flow responses. Our lab recently discovered that the polarity adaptor protein, LGN, which binds directly to VE-Cahderin is important for proper endothelial cell alignment. Since LGN directly interacts with a flow dependent mechanosensitive complex and has an established role regulating cytoskeletal dynamics, I hypothesize LGN is important for flow direction sensing. I plan to address this hypothesis using the following specific aims: Aim 1: Characterize the mechanism by generating mutations in LGN’s functional domains to determine which sites are important for mediating endothelial cell flow dependent signaling. I will similarly examine the effects of known LGN interactors if they are shown to be crucial for flow mediated signaling. Aim 2: Examine the role of cell polarity in flow signaling. I will do this first by tracking the intracellular localization of LGN in response to flow and use patterned substrates to separately constrain cell and cytoskeletal polarity to determine which of these variables is important for LGN polarity and inflammatory vs. anti-inflammatory signaling. Aim 3: Determine the role of LGN in vivo by analyzing mice with endothelial deletion of LGN which will address the role of LGN in VEC alignment, inflammation, and resulting atherosclerosis in vivo. Together, these aims will reveal new mechanisms for endothelial flow sensing, vascular inflammation, and atherosclerotic disease.


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 = $49,538 )
2026	2026	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Blood Diseases and Resources Research	000	3	2/12/2026	NON-COMPETING CONTINUATION	$49,538
														Subtotal = $49,538

Issue Date FY: 2025 ( Subtotal = $49,538 )
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Blood Diseases and Resources Research	000	2	12/20/2024	NON-COMPETING CONTINUATION	$48,974
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Blood Diseases and Resources Research	001	2	9/16/2025	NON-COMPETING CONTINUATION	$564
														Subtotal = $49,538

Issue Date FY: 2023 ( Subtotal = $47,694 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Blood Diseases and Resources Research	001	1	8/23/2023	NEW	$0
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Blood Diseases and Resources Research	000	1	8/23/2023	NEW	$47,694
														Subtotal = $47,694

Grand Total All Awards = $146,770

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Contribution of Endothelial Planar Cell Polarity pathways in Blood Flow Direction Sensing

Award Number: F31HL168920

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/01/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer