Poster abstracts
Poster number 36 submitted by Anuprova Bhowmik
Computational Pathology Analysis Links ESRP2 Dysregulation to Injury Patterns in MetALD
Anuprova Bhowmik (Department of Biochemistry, University of Illinois Urbana-Champaign), Arnab Roy (Department of Biochemistry, University of Illinois Urbana-Champaign), Diptatanu Das (Department of Biochemistry, University of Illinois Urbana-Champaign), Auinash Kalsotra (Department of Biochemistry, University of Illinois Urbana-Champaign)
Abstract:
Metabolic dysfunction and alcohol-associated liver disease (MetALD) arises from the combined effects of high-calorie diet and heavy alcohol use, and is a major cause of liver failure and mortality. Epithelial Splicing Regulatory Protein 2 (ESRP2) is one of the most downregulated RNA-binding proteins in human alcohol-associated liver disease (ALD). ESRP2 is normally expressed in mature hepatocytes but suppressed in the fetal-like proliferative states, suggesting that both gain and loss of function of ESRP2 could be detrimental for ALD pathogenesis. To evaluate how ESRP2 influences liver injury in MetALD, we combined a chronic murine model with quantitative computational pathology. Adult male wild-type (WT), ESRP2-knockout (KO), and ESRP2-overexpression (OE) mice were placed on a Western diet with weekly ethanol binges for 12 weeks.
Computational analysis using QuPath-based classifiers revealed that KO livers developed the most severe pathology, with significantly increased fibrosis, expanded steatosis, and elevated inflammatory infiltration compared to wild-type mice. OE livers displayed altered patterns of injury, indicating that both loss and gain of ESRP2 disrupt hepatocyte homeostasis. Nuclear size analysis showed shifts consistent with biased proliferative and quiescent states, suggesting that chronic injury perturbs ploidy and regenerative balance. These findings establish a computational framework for quantifying injury in MetALD and demonstrate that ESRP2 is essential for coordinating hepatocyte state during chronic liver damage.
Keywords: RNA Processing, Epithelial Splicing Regulatory Protein 2, Liver Disease