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

Jain, Ishita

Permalink

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

Description

Title

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

Author(s)

Jain, Ishita

Issue Date

2022-11-22

Director of Research (if dissertation) or Advisor (if thesis)

Underhill, Gregory

Doctoral Committee Chair(s)

Underhill, Gregory

Committee Member(s)

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

Department of Study

Bioengineering

Discipline

Bioengineering

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

Liver Tissue Engineering, Microenvironment, Biomechanics

Abstract

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.

Graduation Semester

2022-12

Type of Resource

Thesis

Copyright and License Information

Copyright 2022 Ishita Jain

Owning Collections