Department of Cell Physiology and Metabolism, University of Geneva Medical School
Circadian oscillation of biological processes has been described in most of the light-sensitive organisms on earth. It reflects the existence of underlying intrinsic biological clocks with near 24 hour oscillation periods. It is well established that circadian clocks play a crucial role in the regulation of key metabolic processes. Moreover, there is an emerging evidence for connection between metabolic pathologies and the circadian clockwork. The long-term goal of our laboratory is to identify the molecular basis of circadian rhythmicity in rodent and human peripheral tissues in physiological, and in obesity/type 2 diabetes conditions. We have setup the experimental system for long-term recording of circadian reporter oscillations in human primary cultured cells from different tissue types at population and single cell levels. Using this powerful approach, we scrutinize the role of the oscillators present in a- and ß- cells in pancreatic islet function, and the impact of glucose metabolism on a- and ß- cell oscillators, in mouse and human models. Also, human skeletal muscle clock molecular makeup and its roles in regulating myokine secretion and insulin resistance development have been tackled. The prevalence of obesity and diabetes in modern society is taking on enormous proportions. It is therefore of major importance to identify the molecular basis of circadian rhythmicity in rodent and human peripheral tissues in physiological conditions, and upon obesity/T2D. In addition, we are interested in the connection between circadian clock and cancer, and in particular the thyroid cancer. We explore the molecular makeup of human thyroid clocks in physiology and upon thyroid malignancies, in an attempt to bring new insights into the role of circadian clocks in thyroid cancer, and to apply these changes for thyroid malignancies diagnostics in clinics.