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Linan Wang Dissertation.pdf (2.7 MB)

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Proteomic Based Approaches for Differentiating Tumor Subtypes

Wang, Linan
http://rave.ohiolink.edu/etdc/view?acc_num=osu1482248318956052

Abstract Details

2017, Doctor of Philosophy, Ohio State University, 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 great potential in the separation of type A and B thymomas without confounding of potentially overlapping histological features. Clinically, this allows for objective distinguishing of thymoma subtypes A and B3, which have drastically different clinical outcomes. Chapter 4 of this dissertation discuss histone epigenetic regulation through post- translational modification (PTM) and the associated histone crosstalk. Histones are proteins that combine with DNA to form chromatin. The effects of these PTMs on global protein abundance was assessed using stable isotope labeling in cell culture (SILAC) and tandem mass spectrometry (LC-MS/MS) providing a comparison of protein relative abundance between wild type cells and histone mutants. Experimental data showed there was a discrepancy between protein expression and mRNA levels, which is currently a part of ongoing investigation. This series of experiments emphasizes the importance of proteomics in modern day biological science and medical research.
Michael Freitas, PhD (Advisor)
Mark Parthun, PhD (Committee Member)
Kun Huang, PhD (Committee Member)
Charles Hitchcock, MD, PhD (Committee Member)
156 p.
Biomedical Research
Proteomics; Mass Spectrometry; Thymus; Thymoma; Histones; Biomarker; Cancer; Pathology; Post- Translational Modification; Acetylation

Recommended Citations

Citations

  • Wang, L. (2017). Proteomic Based Approaches for Differentiating Tumor Subtypes [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1482248318956052

    APA Style (7th edition)

  • Wang, Linan. Proteomic Based Approaches for Differentiating Tumor Subtypes. 2017. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1482248318956052.

    MLA Style (8th edition)

  • Wang, Linan. "Proteomic Based Approaches for Differentiating Tumor Subtypes." Doctoral dissertation, Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1482248318956052

    Chicago Manual of Style (17th edition)

osu1482248318956052
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This open access ETD is published by The Ohio State University and OhioLINK.