Project description:Head and neck cancers are a complex malignancy comprising multiple anatomical sites, with cancer of the oral cavity ranking among the deadliest and most disfiguring cancers globally. Oral cancer (OC) constitutes a subset of head and neck cancer cases, presenting primarily as tobacco- and alcohol-associated oral squamous cell carcinoma (OSCC), with a 5-year survival rate of ~65%, partly due to the lack of early detection and effective treatments. OSCC arises from premalignant lesions (PMLs) in the oral cavity through a multi-step series of clinical and histopathological stages, including varying degrees of epithelial dysplasia. To gain insights into the molecular mechanisms associated with the progression of PMLs to OSCC, we profiled the whole transcriptome of 66 human PMLs comprising leukoplakia with dysplasia and hyperkeratosis non-reactive (HkNR) pathologies, alongside healthy controls and OSCC. Our data revealed that PMLs were enriched in gene signatures associated with cellular plasticity, such as partial EMT (p-EMT) phenotypes, and with immune response. Integrated analyses of the host transcriptome and microbiome further highlighted a significant association between differential microbial abundance and PML pathway activity, suggesting a contribution of the oral microbiome towards PML evolution to OSCC. Collectively, this study reveals molecular processes associated with PML progression that may help early diagnosis and disease interception at an early stage.
Project description:The objectives of this study were to establish a microbiome profile for oral epithelial dysplasia using archival lesion swab samples to characterize the community variations and the functional potential of the microbiome using 16S rRNA gene sequencing
Project description:Prescription opioids such as oxycodone have been widely used in the United States and have contributed to the ongoing opioid epidemic. While many individuals limit use to prescribed contexts, a subset transitions to misuse and, in some cases, to illicit opioid use. Identifying behavioral and biological factors that predict this vulnerability is critical for improving prevention and intervention strategies. Here, we investigated whether individual differences in behavioral flexibility and gut microbiome composition are associated with future oxycodone intake using a translationally relevant model of oral oxycodone self-administration in male and female Long-Evans rats. We established a model in which distinct intake phenotypes emerged, characterized by animals with high versus low oxycodone consumption. Behavioral flexibility, assessed using a contingency degradation task, was associated with oxycodone intake, identifying it as a potential behavioral biomarker of vulnerability. In parallel, oral oxycodone exposure altered gut microbiome composition, and microbiome features were associated with both behavioral flexibility and drug-taking behavior. These findings support a framework in which individual differences in opioid intake arise from the interaction of pre-existing behavioral traits and biological states, including gut microbiome composition which provides a foundation for identifying predictive biomarkers and developing individualized strategies to mitigate risk for opioid misuse.
