Metabolic status of the human oral mucosa under physiological conditions, upon metabolic stress or following malignant transformation

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The current project is based on the hypothesis that risk factors and co-morbidities, such as the metabolic syndrome, lead to oxidative stress which causes a de-regulation of the carbohydrate metabolism. The resulting so-called Warburg metabolism represents an early and potentially causal event during the development of cancer. Our research will therefore be focused on the metabolic status of human oral mucosa in a normal state, under metabolic stress (by risk factors and co-morbidities) or after malignant transformation. We will characterize glycolysis-related metabolites and proteins, specifically the tissue concentration of ATP, glucose, pyruvate and lactate, as well as the expression level of membrane transporters for cellular glucose uptake (GLUT1/3) and for lactate uptake or excretion (MCT1/4), respectively. The measured parameter values will be correlated with clinical patient data to evaluate their clinical significance. These clinical studies will be supported by cell culture experiments to elucidate molecular mechanisms that underlie the causal link between oxidative stress, Warburg metabolism and malignant transformation. Besides the elucidation of these mechanisms, the ultimate goal of the study is the identification of a set of metabolic parameters which contributes to (i) the improvement of early cancer diagnosis, (ii) the prediction of the degree of malignancy of the disease and (iii) the efficiency of a personalized therapy.