Bishuang Cai, PhD
Role and Regulation of Cholesterol-Associated GWAS Locus EHBP1 in NASH
Summary
Due to the incomplete understanding of the mechanisms of nonalcoholic steatohepatitis (NASH) progression, effective treatment options for NASH are lacking. Emerging experimental and human evidence has revealed that liver cholesterol accumulation is critical for the pathogenesis of NASH. However, how cholesterol is regulated in NASH remains unknown. Human genome-wide association studies (GWAS) have determined that several single-nucleotide polymorphisms in EH domain binding protein 1 (EHBP1) are associated with cholesterol levels, and our data show that EHBP1 expression is reduced in human and mouse NASH livers, which can be reversed by the administration of pro-resolving mediators. The objective of this proposal is to explore the role of EHBP1-mediated cholesterol metabolism in NASH and the mechanism of down-regulated EHBP1 during NASH. The results of this project will contribute significantly to the knowledge of NASH progression and advance a key therapeutic component that will meet the clinical need for novel NASH therapies.
The PhRMA Foundation Research Starter Grant has helped me to build an attractive study for competing for extramural funding.