Graduation Date

Spring 5-10-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Pharmaceutical Sciences

First Advisor

Daryl J. Murry

Abstract

The timely diagnosis of diseases is vital for administering appropriate treatment and improving patient healthcare. To this date, many diseases such as inflammatory bowel disease (IBD), cancer, non-alcoholic fatty liver disease (NAFLD), do not exhibit symptoms until progressing into advanced stages. As a result, physicians are unable to diagnose them and provide timely therapeutic treatment. Moreover, the “one size fits all” approach does always work for such diseases, often rendering the treatment ineffective, and resulting in poor patient compliance and increased medical costs. Thus, precision medicine has gained much importance in the last few years. Biomarkers are important tools that help in diagnosis, monitoring of diseases, and therapeutic response. For years, physicians have relied on biomarkers to assess patient well-being and selection of drugs. However, many diseases cannot be diagnosed in their earlier stage, due to a lack of reliable biomarkers. There is an unmet medical need for development of novel biomarkers for such complex and chronic disorders. This dissertation looks into the typical steps involved in biomarker development. The first chapter focuses on different types of biomarkers, their advantages and disadvantages, the challenges to biomarker discovery, and their potential applications. In second chapter focused on the typical workflow for assay development and validation for an endogenous biomarker indole, which is a potential biomarker for NAFLD, C.difficile infections, assessing the risk of cardiovascular disease in chronic kidney disease, among many others. The subsequent chapters dive into eicosanoids as potential novel non-invasive biomarkers to assess disease progression and drug response for IBD. The third chapter aims to establish the proof of concept for the same using a mouse model of IBD. The fourth chapter evaluates eicosanoids as potential biomarkers to assess disease severity in humans, thereby evaluating them as potential biomarkers of disease progression and resolution. Overall, our research aims to improve precision medicine for complex and chronic disorders by identifying novel potential biomarkers, thereby improving patient outcomes.

Comments

2025 Copyright, the authors

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Available for download on Tuesday, April 27, 2027

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