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Full text release has been delayed at the author's request until May 05, 2025

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Exposing Metabolic Vulnerabilities of Cancer Using Metabolomics

Choueiry, Fouad
http://rave.ohiolink.edu/etdc/view?acc_num=osu1712837338267419

Abstract Details

2024, Doctor of Philosophy, Ohio State University, Nutrition Program, The Ohio State University.
Tumorigenesis relies on cellular metabolism reprogramming driven by oncogenic mutations, profoundly affecting gene expression, cellular differentiation, and the tumor microenvironment. Metabolomics profiling is a potent tool for monitoring tumor metabolism, assessing treatment response, predicting metabolic shifts, measuring drug efficacy, and tracking drug resistance. We investigated lung cancer cell cultures to understand the metabolic processes underlying cancer-associated VOCs and identify related protein-encoding genes. Utilizing SESI-HRMS, we identified VOCs associated with lung cancer, distinguishing between NSCLC and SCLC. Treatment-induced changes in VOC profiles were also observed. To overcome ion competition in data collection, we developed dGOT-SESI-HRMS, leveraging the mVOC database and spectral stitching. Validation with anaerobic bacterial cultures uncovered robust data collection and paved the way for biological interpretation using this novel VOC screening tool. This method enabled robust analysis of the volatilome associated with interventions in mice, revealing unique profiles associated with distinct microbiome compositions and cancer. Our analyses circumvented the metabolic and genetic heterogeneity in humans to established pre-clinical models for standardized VOC analyses. Additionally, mass spectrometry based metabolomics can be a powerful tool when combined with other –omics techniques. Unbiased high-throughput metabolomics techniques uncovered metabolic deregulations associated with acquired ibrutinib resistance in lymphoma and allowed us to construct metabolic maps to reveal key players like IL4I1 influencing metabolic reprogramming. This integrated approach highlights the power of metabolomics for revealing systemic metabolic and volatile changes in cancer cells and facilitates advancements in cancer detection and treatment monitoring for improved outcomes.
Jiangjiang Zhu (Advisor)
Lalit Sehgal (Committee Member)
Rachel Kopec (Committee Member)
Martha Belury (Committee Member)
247 p.
Nutrition
cancer metabolism, metabolomics, volatile organic compounds

Recommended Citations

Citations

  • Choueiry, F. (2024). Exposing Metabolic Vulnerabilities of Cancer Using Metabolomics [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1712837338267419

    APA Style (7th edition)

  • Choueiry, Fouad. Exposing Metabolic Vulnerabilities of Cancer Using Metabolomics. 2024. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1712837338267419.

    MLA Style (8th edition)

  • Choueiry, Fouad. "Exposing Metabolic Vulnerabilities of Cancer Using Metabolomics." Doctoral dissertation, Ohio State University, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=osu1712837338267419

    Chicago Manual of Style (17th edition)

osu1712837338267419
© 2024, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.