University of Illinois at Chicago
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Temporal Dynamics of Gene Regulation in Human Tissue Repair

thesis
posted on 2024-05-01, 00:00 authored by Trevor Robert Thomas Leonardo
Wound healing research most often focuses on understanding the role of individual genes or specific cell types involved. The goal of this thesis was to take a step away from how wound healing research is traditionally conducted and push the boundaries of the field to gain knowledge through a new, network perspective. Specifically, the work in this thesis takes a completely data-driven approach using cutting edge algorithms, a unique human transcriptomic dataset, and network science to better understand both the regenerative and scarring phenotypes of wound healing in adult humans at a network level. If we can identify core regulators of the regenerative response to injury and the scarring response, then we can begin to look for therapeutic treatments to prevent scarring and promote tissue regeneration. Findings from this work should be applicable to tissue injuries in multiple organ systems as cutaneous wounds are a generalized model of wound repair. Chapter I provides an introduction to cutaneous and oral wound healing, transcription factors and gene regulation, network biology, and the PANDA and LIONESS algorithms used in this thesis. Chapter II focuses on the optimization and implementation of a mouse oral palate excisional wound as a tool to investigate oral healing. Chapter III sheds light on the transcriptomic response to injury in human palate and skin with the goals of: 1) Identifying conserved and tissue-specific responses to injury over time and 2) Linking the observed transcriptomic changes to functional pathways. Chapter IV uses a network biology approach to generate sample-specific gene regulatory networks of wound healing in human palate and skin. These networks are used to infer temporal gene targeting changes and to infer the core transcriptional regulators of the regenerative and scarring response to injury. Chapter V is a discussion of the conclusions derived from this work, its relevance to the wound healing field, and future directions.

History

Advisor

Luisa DiPietro

Department

Microbiology and Immunology

Degree Grantor

University of Illinois Chicago

Degree Level

  • Doctoral

Degree name

PhD, Doctor of Philosophy

Committee Member

Kimberly Glass Lester Lau Donna MacDuff Alan McLachlan Adam Oberstein

Thesis type

application/pdf

Language

  • en

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