R35HL155681
Project Grant
Overview
Grant Description
Endogenous Circadian Mechanisms Underlying Cardiovascular Risk - Project Summary/Abstract
Endogenous circadian clocks exist in all cells and tissues, including the autonomic nervous system, heart, and vasculature. The resultant rhythms prepare the cardiovascular (CV) system for optimal function to match the daily anticipated behavioral and environmental cycles, such as altered posture and increased activity after awakening in the morning.
However, the morning is also the most vulnerable time for adverse CV events, including myocardial infarction, stroke, and sudden cardiac death. Dr. Shea has pioneered the use of intensive, multi-day laboratory experiments and uncovered substantial endogenous circadian rhythms across the CV system in healthy humans. Dr. Shea also discovered that circadian rhythms exist in the CV reactivity to stressors (i.e., there are different CV responses to identical stressors at different times of day).
Dr. Shea's work has led to the concept that circadian rhythms in the CV system act as a 'double-edged sword': the normal amplified responses in the morning aid the transition from sleep to activity in healthy individuals, but such exaggerated responses are potentially perilous in individuals with underlying CV risk factors who are susceptible to adverse events.
Dr. Shea will lead a multi-disciplinary team of outstanding investigators to examine the broad question of how the circadian system interacts with behavior-related CV responses to produce predictable daily variations in CV risk profiles. To compare with healthy controls, studies will be performed in populations with increased underlying susceptibility to CV disease, such as hypertension, midlife adults, and obstructive sleep apnea.
The overall team has expertise in circadian, sleep, stress, exercise, and CV physiology, and positron emission tomographic imaging of the balance of pre- and post-synaptic adrenergic function in the left ventricle in resting humans. The investigators will use outstanding purpose-built facilities to perform the necessary intensive, multi-day studies with nursing, bio-nutrition, and clinical support services integrated with the team's physiological expertise.
Dr. Shea has over 30 years' experience performing clinical research mainly focused on circadian rhythms in healthy humans and their impact on CV disease risk factors, and he has performed the majority of the CV physiology studies in humans that use validated circadian protocols. Dr. Shea has been well-funded with 25 consecutive years as PI of investigator-initiated federal grants. Dr. Shea's publications are well-cited with a mean relative citation ratio of 3.84 for original research papers in the past decade [2009-18], which is higher than the 90th percentile for all NIH-funded papers in the same field [NIH Office of Portfolio Analysis: iCite tool]).
Due to the fast-emerging recognition of the magnitude and extent of circadian rhythms throughout the body, including circadian rhythms in drug targets, we are on the cusp of meaningful chronotherapeutic trials in CV medicine that consider internal circadian time. These preclinical studies performed in this research program will provide the critical and timely background needed to fully exploit these opportunities to improve therapy of CV disease.
Endogenous circadian clocks exist in all cells and tissues, including the autonomic nervous system, heart, and vasculature. The resultant rhythms prepare the cardiovascular (CV) system for optimal function to match the daily anticipated behavioral and environmental cycles, such as altered posture and increased activity after awakening in the morning.
However, the morning is also the most vulnerable time for adverse CV events, including myocardial infarction, stroke, and sudden cardiac death. Dr. Shea has pioneered the use of intensive, multi-day laboratory experiments and uncovered substantial endogenous circadian rhythms across the CV system in healthy humans. Dr. Shea also discovered that circadian rhythms exist in the CV reactivity to stressors (i.e., there are different CV responses to identical stressors at different times of day).
Dr. Shea's work has led to the concept that circadian rhythms in the CV system act as a 'double-edged sword': the normal amplified responses in the morning aid the transition from sleep to activity in healthy individuals, but such exaggerated responses are potentially perilous in individuals with underlying CV risk factors who are susceptible to adverse events.
Dr. Shea will lead a multi-disciplinary team of outstanding investigators to examine the broad question of how the circadian system interacts with behavior-related CV responses to produce predictable daily variations in CV risk profiles. To compare with healthy controls, studies will be performed in populations with increased underlying susceptibility to CV disease, such as hypertension, midlife adults, and obstructive sleep apnea.
The overall team has expertise in circadian, sleep, stress, exercise, and CV physiology, and positron emission tomographic imaging of the balance of pre- and post-synaptic adrenergic function in the left ventricle in resting humans. The investigators will use outstanding purpose-built facilities to perform the necessary intensive, multi-day studies with nursing, bio-nutrition, and clinical support services integrated with the team's physiological expertise.
Dr. Shea has over 30 years' experience performing clinical research mainly focused on circadian rhythms in healthy humans and their impact on CV disease risk factors, and he has performed the majority of the CV physiology studies in humans that use validated circadian protocols. Dr. Shea has been well-funded with 25 consecutive years as PI of investigator-initiated federal grants. Dr. Shea's publications are well-cited with a mean relative citation ratio of 3.84 for original research papers in the past decade [2009-18], which is higher than the 90th percentile for all NIH-funded papers in the same field [NIH Office of Portfolio Analysis: iCite tool]).
Due to the fast-emerging recognition of the magnitude and extent of circadian rhythms throughout the body, including circadian rhythms in drug targets, we are on the cusp of meaningful chronotherapeutic trials in CV medicine that consider internal circadian time. These preclinical studies performed in this research program will provide the critical and timely background needed to fully exploit these opportunities to improve therapy of CV disease.
Funding Goals
TO FOSTER HEART AND VASCULAR RESEARCH IN THE BASIC, TRANSLATIONAL, CLINICAL AND POPULATION SCIENCES, AND TO FOSTER TRAINING TO BUILD TALENTED YOUNG INVESTIGATORS IN THESE AREAS, FUNDED THROUGH COMPETITIVE RESEARCH TRAINING GRANTS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Portland,
Oregon
972393011
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 397% from $924,000 to $4,596,491.
Oregon Health & Science University was awarded
Circadian Mechanisms in Cardiovascular Risk: Unveiling Daily Variations
Project Grant R35HL155681
worth $4,596,491
from National Heart Lung and Blood Institute in July 2021 with work to be completed primarily in Portland Oregon United States.
The grant
has a duration of 7 years and
was awarded through assistance program 93.837 Cardiovascular Diseases Research.
The Project Grant was awarded through grant opportunity NHLBI Outstanding Investigator Award (OIA) (R35 Clinical Trial Optional).
Status
(Ongoing)
Last Modified 7/25/25
Period of Performance
7/1/21
Start Date
6/30/28
End Date
Funding Split
$4.6M
Federal Obligation
$0.0
Non-Federal Obligation
$4.6M
Total Obligated
Activity Timeline
Transaction History
Modifications to R35HL155681
Additional Detail
Award ID FAIN
R35HL155681
SAI Number
R35HL155681-4165729790
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled 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
NPSNT86JKN51
Awardee CAGE
0YUJ3
Performance District
OR-01
Senators
Jeff Merkley
Ron Wyden
Ron Wyden
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) | $1,842,971 | 100% |
Modified: 7/25/25