Jiaxun Li
BME MS Thesis Defense Presentation
Date: 2025-03-26
Time: 10:30AM - 12:00PM
Location / Meeting Link: IBB 3316 https://gatech.zoom.us/j/97408044082 

Committee Members:
Dr. Ahmet Coskun (Advisor); Dr. Aniruddh Sarkar; Dr. Shu Jia


Title: Spatial Mapping and Interaction Analysis of Protein Profile in Liver Fibrosis Using Multiplexed Imaging

Abstract:
Liver fibrosis is a significant health concern that affects approximately 300 million people globally, characterized by the excessive accumulation of extracellular matrix (ECM) components in the liver. A major contributor to liver fibrosis is fatty liver disease (FLD), which can progress to steatohepatitis when the accumulation of fat in the liver causes inflammation, cell death, and scarring. Long-standing steatohepatitis leads to liver fibrosis as scar tissue builds up and replaces healthy liver tissue, potentially progressing to life-threatening conditions such as cirrhosis, liver failure, or hepatocellular carcinoma (HCC). Epigenetic modifications, including DNA methylation, play a critical role in the development and progression of fatty liver disease (FLD) and liver fibrosis by altering gene expression without modifying the DNA sequence. The integration of spatial analysis with protein profiling further enhances our ability to explore the spatial organization of cellular interactions and protein expression in liver diseases, fostering a deeper understanding of the disease mechanisms. The multiplexed immunofluorescent imaging was performed to understand the spatial organization of 10 molecular targets and the cellular interaction between them across four distinct liver tissue types: wild-type (WT) regular, WT high-fat, fibrosis regular, and fibrosis high-fat. Spatial correlations, colocalization, clustering, spatial proximity analyses, and visualization were conducted at the single-cell level, revealing complex relationships between DNA methylation, ECM, and structural proteins. In diseased tissues, increased ECM correlates with higher methylation levels, further supporting the established role of methylation in ECM progression. These findings provide new spatial and single-cell insights into this regulatory mechanism, offering a deeper understanding of the interplay between methylation, ECM, and structural proteins in liver fibrosis and FLD.