Doctor of Philosophy, The Ohio State University, 2017, Biomedical Sciences

In medicine, successful patient treatment relies on early and accurate diagnosis. Following diagnosis disease specific and effective treatments are necessary, targeting affected cells while sparing normal tissue. While past studies have focused on genomics, the importance of transcriptomics and proteomics is increasingly understood. Proteomics, the study of proteins, will be the focus of this dissertation. Proteomics provide insight in the post transcriptional and translational regulation of proteins, information not available through the study of DNA and RNA alone. These effects play an important role in protein quantity and physiological function. It is well established that changes in protein homeostasis are associated with disease conditions, hence providing the grounds for biomarker discovery. It has been shown that if homeostasis can be restored, disease conditions can be reversed, further emphasizing the role of proteomics in therapeutic target discovery. Chapter 1 highlights the importance of proteomics in the field of biomedical research with an emphasis on clinical translational sciences in moving discoveries from bench to bedside. Chapters 2 of this dissertation describe the development of methodology for the study of archived clinical biopsy samples. Following biopsy, patient tissue is preserved with formalin fixation and paraffin embedding (FFPE) and archived. Such tissue is stable for research for decades. This document will describe a method to prepare this tissue in for proteomic studies using LC-MS/MS with a novel on-slide digestion technique to be used with manual microdissection. Then using this technique, possibility to distinguish the different thymoma subtypes with a proteomics approach was investigated to provide an objective diagnosis tool to complement the current histological diagnosis. In Chapter 3, desmoyokin, a protein found to be unique to the medulla of the thymus and not present in the cortex will be described. This protein holds g (open full item for complete abstract)

Committee: Michael Freitas PhD (Advisor); Mark Parthun PhD (Committee Member); Kun Huang PhD (Committee Member); Charles Hitchcock MD, PhD (Committee Member) Subjects: Biomedical Research