Madison Shiyuk

Topic

Investigating tumor metabolism with mass spectrometry imaging

Department of Biochemistry and Microbiology

Date & location

• Wednesday, May 13, 2026
• 9:00 A.M.
• Clearihue Building, Room B017

Examining Committee

Supervisory Committee

• Dr. David Goodlett, Department of Biochemistry and Microbiology, University of Victoria (Supervisor)
• Dr. Julian Lum, Department of Biochemistry and Microbiology, UVic (Member)
• Dr. Helena Petrosova, Department of Biochemistry and Microbiology, UVic (Member)
• Dr. Kyle Duncan, Department of Chemistry, UVic (Outside Member)

External Examiner

• Dr. Seth Parker, Department of Biochemistry and Molecular Biology, University of British Columbia

Chair of Oral Examination

• Dr. Chris Gill, Department of Chemistry, UVic

Abstract

Tumor metabolism plays a critical role in shaping the tumor immune microenvironment and contributes to immunosuppression in cancer. In ovarian cancer, metabolic competition and accumulation of immunoregulatory metabolites can impair T cell activation and promote exhaustion, resulting in immunotherapeutic resistance and poor patient outcomes. These tumors are highly heterogeneous, and metabolic interactions between cancer cells and immune cells often occur within spatially restricted microenvironments. Thus, mass spectrometry imaging (MSI) has emerged as a powerful technique for spatial metabolomics, enabling label-free mapping of metabolites and lipids directly within tissue sections while preserving tissue organization. However, several analytical limitations remain for spatial profiling of tumor immune microenvironments. Small molecules, such as methionine cycle metabolites, are implicated in immune modulation in tumors, yet they remain difficult to detect using conventional approaches for matrix-assisted laser desorption/ ionization mass spectrometry imaging (MALDI MSI). Further, use of a single MSI modality results in inherent specificity for target molecular classes, motivating development of multimodal workflows integrating two or more MSI approaches.

The objective of this work was to develop and apply MSI-based workflows to investigate metabolic heterogeneity within the tumor immune environment. Methodological approaches were established for spatial detection of methionine cycle metabolites using MALDI MSI with on-tissue chemical derivatization. A complementary multimodal workflow was developed to support multimodal imaging experiments combining metabolite, lipid, and immune marker detection within tumor tissues.

Application of multimodal workflows revealed spatial metabolic differences associated with immune cell infiltration in murine tumor models and human ovarian cancer specimens. Regions enriched for CD8+ T cells exhibited distinct metabolic signatures, including increased abundance of several amino acids and lipids containing arachidonic acid fatty acyl chains. Together, this work demonstrates the utility of mass spectrometry imaging for spatially resolving metabolic features of the tumor immune microenvironment and provides technical foundations for integrating metabolite, lipid, and protein imaging to study immune-metabolic interactions in cancer.