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

Decoding endothelial metabolic control of liver homeostasis and response to damage.

Award Number: R01DK148866
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/10/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2031

Group Awards By:

View Award Description

Decoding endothelial metabolic control of liver homeostasis and response to damage. - PROJECT SUMMARY / ABSTRACT Chronic liver disease affects over 4.5 million Americans, requiring of liver transplant by the time it degenerates into cirrhosis. While the clinical manifestations of liver failure affect primarily the hepatocytes, it has been shown that other non-parenchymal cells in the liver sustained an important function in the maintenance of liver function. The endothelial cells (ECs) that line the blood vessels of the liver are highly specialized cells that secrete organotypic factors that control hepatocyte function and zonation, including HGF, Wnt2, Wnt9b and Rspo3 among others. Previous studies of the transcriptional regulation of liver sinusoidal endothelial cells (LSECs) have found cooperation between generic EC genes, such as Erg and Fli1, together with liver EC specific genes such as c-Maf and Gata4 in the orchestration of the LSEC phenotype. However, during the development of liver fibrosis, LSECs lose their specialization and acquire a more generic capillary EC phenotype, in a process known as capillarization. While the transcriptional profile of how LSECs change during liver fibrosis have been well documented, little is known of the molecular and cellular adaptation of LSECs during the capillarization process. We hypothesize that changes in the metabolic regulation of LSECs are behind the capillarization process leading to the loss of their sinusoidal status. This capillarization changes also leads to an increase inflammatory response of the ECs, attracting an increased number of inflammatory cells. Understanding the molecular mechanisms driving LSEC adaptation and it's lost during liver fibrosis can provide with novel cues in the treatment of liver disease. We have identified that LSEC adaptation is partially driven through changes in cell shape and adaptation of its mitochondria. These results point towards a central role of the mTOR pathway in the control of LSEC cell shape and function, as well as in the adaptation towards an oxidative phosphorylation phenotype with a central role for mitochondrial metabolism. In this grant we propose to study how this pathways control LSEC metabolic adaptation and how their alteration can lead to liver fibrosis. Furthermore, using a human induce LSEC reprogramming model, previously developed in our laboratory, we will study how these pathways are maintained in humans and their importance in the regulation of human liver sinusoids. Our team of molecular-vascular biologist and hepatologist is uniquely suited to pioneer the understanding of how vascular metabolic regulation of LSECs drives liver fibrosis and applied this knowledge towards future liver vascular therapy.


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 = $585,556 )
2026	2026	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/7/2026	NEW	$585,556
														Subtotal = $585,556

Grand Total All Awards = $585,556

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Decoding endothelial metabolic control of liver homeostasis and response to damage.

Award Number: R01DK148866

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/10/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer