R01HL169510
Project Grant
Overview
Grant Description
Flow regulation of the ALK1/ENG pathway in vascular homeostasis and disease - Project Summary
Fluid shear stress-dependent vessel remodeling is an essential regulatory mechanism in embryonic development and in adult vascular homeostasis where it optimizes blood flow to target tissues. Conversely, un- or mis-regulated remodeling results in vascular malformations, while poor remodeling is a key aspect of blood flow restriction in coronary and peripheral artery disease.
Our preliminary data reveal the existence of a regulatory network with two mutually inhibitory states, one associated with vessel stability and one with physiological outward remodeling or pathological AVM formation. These results allow us to propose a unifying hypothesis that links physiological and pathological remodeling, and suggest the existence of control points that can be manipulated to either increase or decrease vascular lumen diameter.
The project aims to elucidate these regulatory mechanisms and then harness these new insights to investigate their relevance to vascular development, to identify therapeutic targets for HHT patients who suffer from excessive pathological remodeling, and identify therapeutic targets for coronary and peripheral artery disease patients where physiological remodeling is impaired.
We will define the molecular basis of this novel EC shear stress mechanism, determine its biological role, and develop and test therapeutic applications based on this knowledge.
Fluid shear stress-dependent vessel remodeling is an essential regulatory mechanism in embryonic development and in adult vascular homeostasis where it optimizes blood flow to target tissues. Conversely, un- or mis-regulated remodeling results in vascular malformations, while poor remodeling is a key aspect of blood flow restriction in coronary and peripheral artery disease.
Our preliminary data reveal the existence of a regulatory network with two mutually inhibitory states, one associated with vessel stability and one with physiological outward remodeling or pathological AVM formation. These results allow us to propose a unifying hypothesis that links physiological and pathological remodeling, and suggest the existence of control points that can be manipulated to either increase or decrease vascular lumen diameter.
The project aims to elucidate these regulatory mechanisms and then harness these new insights to investigate their relevance to vascular development, to identify therapeutic targets for HHT patients who suffer from excessive pathological remodeling, and identify therapeutic targets for coronary and peripheral artery disease patients where physiological remodeling is impaired.
We will define the molecular basis of this novel EC shear stress mechanism, determine its biological role, and develop and test therapeutic applications based on this knowledge.
Awardee
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Connecticut
United States
Geographic Scope
State-Wide
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 290% from $775,568 to $3,021,299.
Yale Univ was awarded
Regulation of ALK1/ENG Pathway in Vascular Remodeling
Project Grant R01HL169510
worth $3,021,299
from National Heart Lung and Blood Institute in July 2023 with work to be completed primarily in Connecticut United States.
The grant
has a duration of 3 years 10 months and
was awarded through assistance program 93.837 Cardiovascular Diseases Research.
The Project Grant was awarded through grant opportunity NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 5/21/26
Period of Performance
7/15/23
Start Date
5/31/27
End Date
Funding Split
$3.0M
Federal Obligation
$0.0
Non-Federal Obligation
$3.0M
Total Obligated
Activity Timeline
Subgrant Awards
Disclosed subgrants for R01HL169510
Transaction History
Modifications to R01HL169510
Additional Detail
Award ID FAIN
R01HL169510
SAI Number
R01HL169510-1871370268
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Private Institution Of Higher Education
Awarding Office
75NH00 NIH National Heart, Lung, and Blood Institute
Funding Office
75NH00 NIH National Heart, Lung, and Blood Institute
Awardee UEI
FL6GV84CKN57
Awardee CAGE
4B992
Performance District
CT-90
Senators
Richard Blumenthal
Christopher Murphy
Christopher Murphy
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Heart, Lung, and Blood Institute, National Institutes of Health, Health and Human Services (075-0872) | Health research and training | Grants, subsidies, and contributions (41.0) | $775,568 | 100% |
Modified: 5/21/26