Monday, February 16, 2026 2/16/2026

Novel Targets for Reducing Atherosclerosis in Type 1 Diabetes

Award Number: R01HL161092
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2026

Group Awards By:

View Award Description

Novel Targets for Reducing Atherosclerosis in Type 1 Diabetes - Atherosclerosis pathogenesis is multifactorial, involving hyperlipidemia and inflammation, as well as hyperglycemia. Individuals with type 1 diabetes show a four-fold increase in cardiovascular disease risk that has persisted despite the spectacular advances in drugs for risk factor management and insulin therapy4. Thus, new strategies and approaches are necessary. Because insulin is administered to diabetic patients subcutaneously, rather than into the portal vein, which is physiological, the liver remains relatively under-insulinized. We considered the possibility that this could contribute to the pro-atherogenic milieu, even beyond hyperglycemia. The long-term goal of this project is to develop drugs that mimic key atheroprotective effects of insulin on the liver. In our preliminary data, we identify Cyp7b1 as an exquisitely sensitive target of insulin in the liver: Cyp7b1 was increased by acute insulin stimulation; reduced by insulin deficiency; reduced by hepatic knockout of the insulin receptor; and one of only four genes significantly altered in all three conditions. CYP7B1 plays a central role in cholesterol, oxysterol and bile acid metabolism6-8. Based on our strong preliminary data, we hypothesize that insulin induces CYP7B1 to maintain lipid homeostasis and suppress inflammation, and that this regulation is lost in type 1 diabetes, leading to atherosclerosis. To test this hypothesis, we will (1) determine the extent to which restoration of Cyp7b1 in a mouse model of type 1 diabetes can prevent atherosclerosis; and (2) define the signaling pathways by which insulin regulates Cyp7b1. We expect to find that CYP7B1 reduces atherosclerosis in diabetic mice via two mechanisms: (1) reducing oxysterols and vascular inflammation; and (2) reducing dietary cholesterol absorption (via modulation of the bile acid profile) and plasma cholesterol. Validation of our hypothesis could lead to the development of drugs that mimic insulin action on CYP7B1. Such drugs, which would restore homeostasis in type 1 diabetes, could be more effective than present lipid-lowering therapies as they would lower both plasma cholesterol and inflammation.


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: 2025 ( Subtotal = $694,247 )
2025	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	000	4	11/20/2024	NON-COMPETING CONTINUATION	$624,822
2025	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	001	4	8/20/2025	NON-COMPETING CONTINUATION	$69,425
2025	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	002	4	9/9/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $694,247

Issue Date FY: 2024 ( Subtotal = $669,816 )
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	000	3	11/27/2023	NON-COMPETING CONTINUATION	$615,137
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	001	3	6/26/2024	NON-COMPETING CONTINUATION	$54,679
														Subtotal = $669,816

Issue Date FY: 2023 ( Subtotal = $683,486 )
2023	2023	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	000	2	11/30/2022	NON-COMPETING CONTINUATION	$615,137
2023	2023	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	001	2	2/11/2023	NON-COMPETING CONTINUATION	$68,349
														Subtotal = $683,486

Issue Date FY: 2022 ( Subtotal = $687,026 )
2022	2022	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	000	1	11/24/2021	NEW	$687,026
														Subtotal = $687,026

Grand Total All Awards = $2,734,575

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Novel Targets for Reducing Atherosclerosis in Type 1 Diabetes

Award Number: R01HL161092

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer