Translational Chronobiology and Chronomedicine
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 emerging evidence for a 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 obesity/type 2 diabetes conditions. We have set up an experimental system for long-term recording of circadian reporter oscillations in human primary cultured cells from different tissue types at both population and single-cell levels. Using this powerful approach, we scrutinize the role of the oscillators present in α- and β-cells in pancreatic islet function, and the impact of glucose metabolism on α- and β-cell oscillators in mouse and human models. Additionally, we investigate the molecular makeup of the clocks in human skeletal muscle and white adipose tissue, and roles of circadian regulation in muscle and adipose tissue function in physiological context, and under diabetes associated insulin resistance. Furthermore, we explore circadian rhythms in the enteroendocrine cells in rodents and humans, using 3D organoid models to understand cell-autonomous clocks in intestinal cell types and their implications for GLP1 regulation in metabolic diseases. 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 e\upon obesity/T2D. In addition, we are interested in the connection between the circadian clock and cancer, particularly 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, parathyroid, and lung cancer and to apply these findings for diagnostics and therapy of these malignancies in clinics.
PHD THESES
Dr. Phillip Alexander Keller Andersen 2024
Dr. Weronika Karolina Spaleniak 2023
Dr. Laurent Perrin, 2018
Dr. Anne-Marie Makhlouf, 2017