Exploring the complexities of the tissue microenvironment using high throughput protein microarrays

The tissue microenvironment is a dynamic and incredibly complex system responsible for directing cellular responses and maintaining homeostasis. One noncellular aspect of the tissue microenvironment is the extracellular matrix (ECM) which is constantly degraded, remodeled, and deposited to maintain the tissue’s mechanical properties and tissue homeostasis. The ECM physically supports the cells and provides them with anchorage, as well as distributing biochemical and biomechanical cues that cells can receive and to which they respond. The ECM composition and organization is unique to each tissue and can contain over 150 different ECM components. Dysregulation of the ECM can be both a symptom and promoter of disease. The tissue microenvironment surrounding diseases like cancers and endometriosis is distinctly different in composition, organization, and stiffness from the healthy tissue. The tissue microenvironment is a complex system that cannot be easily replicated in vitro. However, to understand the significance of specific ECM components and changes in the tissue microenvironments, the system must be simplified and systematically broken down without sacrificing physiological relevance and in vivo-like behavior. My research utilizes three diseases as case studies for the role of tissue microenvironment on cellular response and behavior. Hepatocellular carcinoma (HCC), endometriosis, and pancreatic adenocarcinoma (PDAC) are all characterized by dynamically changing ECM microenvironments that support disease progression. In addition, all three diseases have demonstrated tissue tropism where they spread & invade, providing the opportunity to identify key environments that support adhesion and invasion. Fibrosis is also associated with each of these diseases, where the microenvironment surrounding the tumor or lesion is much stiffer than the surrounding healthy tissue. The cells in each disease also exhibit direct control over the ECM composition and organization of their environment to make a supportive environment for disease progression. The objective of this work is to develop and implement a high throughput protein microarray system that recapitulates as much of the complexity of the disease tissue microenvironment as possible while maintaining statistical rigor to increase our understanding of the tissue microenvironment in influencing diseased cell responses.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Bioengineering

Grantor

University of Illinois Urbana-Champaign

Year dc:date

2025

Author dc:creator

• Kimmel, Hannah Rosene Conover

Contributors dc:contributor

• Underhill, Gregory H
• Harley, Brendan A
• Leggett, Susan
• Sirk, Shannon

• Tissue Microenvironment
• ECM
• Design of experiments
• High throughput
• Cancer
• Endometriosis

Statement dc:rights

• Copyright 2025 Hannah Kimmel

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/129523

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F129523