Delineating the interplay of biomechanical cues with cell-cell signaling and epigenetics in liver differentiation and fibrosis

Liver disease is a major public health concern, and one of the key sources of tissue and organ dysregulation in liver disease is the onset of liver fibrosis. Liver has an immense capacity to repair and regenerate, which is also impaired in later stages of liver fibrosis. Over the past decade, the demand for liver transplant has been increasing. There are multiple chronic diseases that lead to liver failure, and subsequent loss of regeneration capacity. The major proportion of candidates listed on the waiting list for transplant have been diagnosed with either Alcoholic Liver disease or liver disease due non-alcoholic fatty liver disease (NAFLD). This proportion has also been increasing over the past decade, due to the higher prevalence of diabetes and obesity. This thesis focuses on developing tools and studies to meet and/or reduce this increasing clinical need for liver transplants. I have developed in vitro platforms to study the microenvironmental control of disease phenotype and basic developmental processes. The objective of the study was to examine how combinations of various microenvironmental factors such the extracellular matrix, substrate stiffness and cellular forces affect cellular behavior in the context of liver fibrosis and liver development. Liver fibrosis produces changes in the composition of the liver and has profound repercussions for cell behavior and function, especially in tissue microenvironments. The makeup and configuration of the microenvironment is critical in directing cell behaviors due to the myriad extracellular cues it presents. Cellular microarray technology is a powerful platform for efficiently and robustly dissecting the effects of multiple microenvironmental parameters simultaneously. The basic understanding of the complex behavior of liver cells and delineating the various factors affecting their behavior is crucial to design better interventions for chronic liver disease and ultimately developing artificial livers for transplants.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Bioengineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2022

Author dc:creator

• Jain, Ishita

Contributors dc:contributor

• Underhill, Gregory
• Harley, Brendan
• Wagoner Johnson, Amy
• Sirk, Shannon

• Liver Tissue Engineering
• Microenvironment
• Biomechanics

Statement dc:rights

• Copyright 2022 Ishita Jain

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/117754

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F117754