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Charbel Darido
Peter MacCallum Cancer Centre, AustraliaPresentation Title:
Defective epithelial differentiation drives the malignant progression of bacteria-colonised precancerous lesions
Abstract
Oral squamous cell carcinomas (OSCC), the most common head and neck malignancy, is a progressive disease that harbours tumour-associated microbiotas. We have identified a mechanism through which indigenous oral bacteria colonise premalignant lesions and mark their malignant progression. During premalignancy, defective epithelial differentiation simultaneously induces chronic barrier impairment and suppresses host defence mechanisms, facilitating intralesional bacterial niche formation. While bacterial tissue location was independent of malignant potential, we found that bacteria exclusively colonised lesions which progressed to cancer, while regressive lesions remained bacteria-free. Multiomics analysis and functional assays revealed that differentiation defects suppressed antibacterial pyroptosis and IL-1B signalling by reducing LPS internalisation in epithelial cells. Furthermore, antibiotic treatment of bacteria-containing lesions reduced disease severity by activating host defense mechanisms. Our findings uncover a role for epithelial differentiation in directing antimicrobial responses and identify intralesional bacteria as both a biomarker of precancer progression and an actionable preventative target in early-stage disease.
Biography
Dr Darido graduated with a Master in Endocrinology and a Master in Physiology before completing his PhD studies on colon cancer at the University of Montpellier, France. He then undertook two post-doctoral trainings in Melbourne and in 2016, he established a comprehensive vibrant research program in head and neck cancer at the newly established Peter Mac Cancer Institute. This is the only fundamental lab-based research program in this area at Peter Mac. Dr Darido’s laboratory is currently investigating the initiating lesions of head and neck cancer as well as the oncogenic drivers of metastatic oral squamous cell carcinoma (OSCC). He is internationally recognised for his work developing pre-clinical human and animal models of OSCC and applying them to study the biology driving invasive disease and identify novel druggable therapeutic targets. His goal is to translate molecular insights into new means of preventing and treating head and neck cancer, which causes much mortality and morbidity worldwide.
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