Browsing by Author "Giddey, Alexander D"

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Comparative proteomic analysis of saliva from chewing tobacco users and oral cancer patients reveals shared biomarkers: A case control observational study
(2024) Giddey, Alexander D
Abstract Objective: The aim of this study was to compare the salivary proteomic profile of smokeless tobacco users with that of non-users and oral cancer patients using Liquid Chromatography-Mass Spectrometry/ Mass Spectrometry (LC-MS/MS). Methods: Saliva samples from 65 participants were collected in three groups: control (25 participants), smokeless tobacco users (25 participants), and oral cancer (15 participants). Results: The analysis revealed 343 protein groups with significantly altered abundance in the saliva samples ( P < 0.05). Among these, 43 out of 51 dysregulated proteins in the smokeless tobacco group were also dysregulated in the oral cancer group. Notably, Apolipoprotein A1 (ApoA1) and Pon1 were found to be significantly increased in both smokeless tobacco users and oral cancer patients ( p < 0.05). Furthermore, six out of the 20 most significantly altered proteins were mitochondrial proteins, and all of these were decreased relative to controls in both smokeless tobacco users and cancer samples. Conclusion: The proteomic profile of users of chewing (smokeless) tobacco (SLT) shows substantial overlap in the altered pathways and dysregulated proteins with those altered in oral cancer samples, suggesting that SLT use induces a shift toward an oncogenic state. Specifically indicated pathways included blood microparticles, platelet α-granules and protease inhibitors as well as indicators of oxidative stress and exogenous compound processing. What differentiates oral cancer samples from SLT users is enrichment of alterations related to cytoskeletal organisation and tissue remodelling.
Multi-Omics Profiling of Candida albicans Grown on Solid Versus Liquid Media
(2023-11) Giddey, Alexander D
Abstract: Candida albicans is a common pathogenic fungus that presents a challenge to healthcare facilities. It can switch between a yeast cell form that diffuses through the bloodstream to colonize internal organs and a filamentous form that penetrates host mucosa. Understanding the pathogen's strategies for environmental adaptation and, ultimately, survival, is crucial. As a complementary study, herein, a multi-omics analysis was performed using high-resolution timsTOF MS to compare the proteomes and metabolomes of Wild Type (WT) Candida albicans (strain DK318) grown on agar plates versus liquid media. Proteomic analysis revealed a total of 1793 proteins and 15,013 peptides. Out of the 1403 identified proteins, 313 proteins were significantly differentially abundant with a p-value < 0.05. Of these, 156 and 157 proteins were significantly increased in liquid and solid media, respectively. Metabolomics analysis identified 192 metabolites in total. The majority (42/48) of the significantly altered metabolites (p-value 0.05 FDR, FC 1.5), mainly amino acids, were significantly higher in solid media, while only 2 metabolites were significantly higher in liquid media. The combined multi-omics analysis provides insight into adaptative morphological changes supporting Candida albicans' life cycle and identifies crucial virulence factors during biofilm formation and bloodstream infection.
Multi-Omics Profiling of Candida albicans Grown on Solid Versus Liquid Media
(2023-11) Giddey, Alexander D
Abstract: Candida albicans is a common pathogenic fungus that presents a challenge to healthcare facilities. It can switch between a yeast cell form that diffuses through the bloodstream to colonize internal organs and a filamentous form that penetrates host mucosa. Understanding the pathogen's strategies for environmental adaptation and, ultimately, survival, is crucial. As a complementary study, herein, a multi-omics analysis was performed using high-resolution timsTOF MS to compare the proteomes and metabolomes of Wild Type (WT) Candida albicans (strain DK318) grown on agar plates versus liquid media. Proteomic analysis revealed a total of 1793 proteins and 15,013 peptides. Out of the 1403 identified proteins, 313 proteins were significantly differentially abundant with a p-value < 0.05. Of these, 156 and 157 proteins were significantly increased in liquid and solid media, respectively. Metabolomics analysis identified 192 metabolites in total. The majority (42/48) of the significantly altered metabolites (p-value 0.05 FDR, FC 1.5), mainly amino acids, were significantly higher in solid media, while only 2 metabolites were significantly higher in liquid media. The combined multi-omics analysis provides insight into adaptative morphological changes supporting Candida albicans' life cycle and identifies crucial virulence factors during biofilm formation and bloodstream infection.