Graduation Year

2024

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Chemistry

Major Professor

Kenyon G. Daniel, Ph.D.

Co-Major Professor

Wayne C. Guida, Ph.D.

Committee Member

James W. Leahy, Ph.D.

Committee Member

Dmitri V. Voronine Ph.D.

Keywords

Biochemical Assay Development, Drug Discovery, STING, Cancer Immunotherapy, Trace Metal Analysis, ICP-OES, Membrane Imaging, SERS, AFM, Aluminum Plasmonic

Abstract

This dissertation endeavors to advance the frontiers of analytical chemistry by addressing critical challenges across three distinct chapters. In the first chapter, the focus is on the evaluation of digestion methods for the analysis of trace metals in mammalian tissues and the Standard Reference Material NIST 1577c. The primary goal is to optimize methodologies, laying the groundwork for reliable trace metal analysis and furthering our understanding of their roles in biological systems.

Transitioning into the realm of immunomodulation, the second chapter elucidates immune response, disease and treatment through the optimization and discovery of STING modulators, utilizing the luciferase assay for real-time measurements of human cells. This chapter aims to deepen our understanding of immune mechanisms and provide a platform for the development of novel immunotherapies, addressing diseases characterized by dysregulated immune responses.

The plasma membrane of cancer cells displays differences in lipid and protein composition which distinguish them from healthy cells. Certain molecules have such prominent vibrational characteristics that they can be considered cancer biomarkers. The final chapter addresses a study applying Surface-enhanced Raman scattering (SERS) imaging of ovarian cancer cells on rough aluminum substrates. We used atomic force microscopy (AFM) to compare cancerous and normal human ovarian cell lines and discuss lipid/protein peak ratios in cytoplasm and nucleus-proximal areas. We suggest the potential of Raman signatures from ovarian and other types of cancer for use as new biomarkers. This method may be extended to other types of cancer biosensing based on aluminum plasmonics.

The diverse approaches employed in each chapter underscore the overarching objective of advancing analytical techniques for applications in biophysics, therapeutic development, and medical diagnostics. Results across these chapters contribute methodologies for reliable trace metal analysis, insights into immune modulation, and novel approaches to cancer diagnosis. The significance of this work extends beyond the laboratory by impacting immunology, cancer research, analytical instrumentation and medical diagnostics. This dissertation holds practical implications for improving human health, pharmacology and drug discovery by addressing these multifaceted challenges.

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