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

Functional identification of non-coding variants associated with metabolic dysfunction-associated steatotic liver disease

Award Number: K01DK138281
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 01/01/2025
PERIOD OF PERFORMANCE END DATE: 11/30/2029

Group Awards By:

View Award Description

Functional identification of non-coding variants associated with metabolic dysfunction-associated steatotic liver disease - Abstract/Project Summary Metabolic dysfunction-associated steatotic liver disease (MASLD) typically initiates as a benign and reversible condition. However, a subgroup of MASLD patients progresses to a severe stage known as metabolic dysfunction-associated steatohepatitis (MASH), often leading to hepatocellular carcinoma and liver failure. Given the global prevalence of MASLD, the significant heterogeneity among patients emphasizes the necessity to efficiently allocate medical resources by identifying those at high risk. Like many other complex diseases, MASLD's occurrence and progression stem from a combination of genetic background and environmental factors. Although genome-wide association studies (GWAS) have identified numerous genetic variants associated with MASLD, their causality and functional roles, especially in non-coding regions, remain largely unexplored. To bridge this gap, we curated a list of non-coding variants from GWAS and prioritized them based on cis-regulatory activity. Integrating in vitro and in vivo analyses of cis-regulatory activity led to the identification of potentially functional regulatory variants (FrVar), hypothesized to predict MASLD genetic risk. Leveraging the Candidate's expertise in functional genomics and bioinformatics, the proposed research aims to elucidate the cis-regulatory function of FrVar in a cell-type-specific manner by manipulating their activity in iPSC-derived liver cells and organoids (Aim 1). Furthermore, the study will investigate alterations in transcription factor binding by FrVar, with a particular focus on EGR1, in iPSC-derived liver cultures modeling MASLD/MASH (Aim 2). Finally, to comprehensively evaluate the clinical value of FrVar, polygenic risk scores will be constructed and their predictive power assessed using biobank data (Aim 3). These endeavors seek to unravel the molecular mechanisms and translational values of non-coding variants in MASLD onset and progression, offering insights into patient risk stratification and management. The accomplishment of these objectives will enhance the Candidate's growth in MASLD studies, emphasizing a stronger focus on human relevance. This proposal will also facilitate the Candidate's professional development in laboratory management and leadership, thereby establishing a solid foundation for an independent research program in the MASLD field.


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 = $145,070 )
2026	2026	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/2/2025	NON-COMPETING CONTINUATION	$145,070
														Subtotal = $145,070

Issue Date FY: 2025 ( Subtotal = $146,570 )
2025	2025	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	12/23/2024	NEW	$146,570
														Subtotal = $146,570

Grand Total All Awards = $291,640

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Functional identification of non-coding variants associated with metabolic dysfunction-associated steatotic liver disease

Award Number: K01DK138281

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 01/01/2025

PERIOD OF PERFORMANCE END DATE: 11/30/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer