ORCID Identifier(s)

0009000834775812

Graduation Semester and Year

Fall 2024

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry

Department

Chemistry and Biochemistry

First Advisor

Saiful M Chowdhury

Second Advisor

Hasan Zaki

Third Advisor

Byung Ran So

Fourth Advisor

Kwangho Nam

Fifth Advisor

Kevin A Schug

Abstract

Two experimental projects with large-scale, mass spectrometry-based proteomics to identify novel therapeutic targets for injury based and inflammatory diseases were implemented.

Second discusses project 1 related to traumatic brain injury. It is a major cause of death and disability worldwide. The study employed a low-cost and efficient impactor model. This model replicated a pathophysiology, commonly observed in human brain injury caused by acceleration–deceleration forces. Many of neuroblastoma cell line, SH-SY5Y cell characteristics are representative of certain important classes of neurological disorders.

Stringent filtering of impacted samples identified 280 proteins of variable expression due to impact. Proteins were categorized into gene ontology classes based on panther classification system, such as ten molecular function, ten biological, two cellular component, fifteen protein classes and four pathway classes.

Among the proteins, Beta-actin-like protein 2, Non-muscle myosin heavy chain IIA, Glyceraldehyde-3-phosphate dehydrogenase, Lactoferrin and Plectin. The study discovered these proteins’ potential to go through further validation studies for involvement with TBI. The study provided a cheaper alternate impactor model with multiplexing capability as well.

Chapter 3 discusses project 2, where the study wanted to discover key proteins in the proteomes of NLRP3 activated macrophages. Monocytic cells THP-1 were subjected to priming treatment with lipopolysaccharide and then activating treatment with monosodium-urate or Nigericin or adenosine triphosphate. Microscopic observation of cells showed pyroptotic cells leaking cellular material in the media. Around 79 proteins were exclusively expressed after NLRP3 inflammasome activation. Proteins were classified by gene ontology-based panther classification into clusters of molecular function, cellular location and biological pathways. Identified proteins participated in splicing, binding and catalytic activities in the nuclear regions. Identified list of proteins in the project provides options for exploring their therapeutic potential for NLRP3 related disorders.

Proteomics studies in two projects provided target protein information for diagnostic and prognostic disease biomarkers.

Keywords

Mass spectrometry, Proteomics, Inflammasome, Traumatic brain injury, Biomarker

Disciplines

Biotechnology | Immunopathology | Molecular and Cellular Neuroscience | Molecular Biology | Systems Biology

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