Translational Chronobiology and Chronomedicine

Your metabolism runs on a schedule. Aligning with your body’s natural timing may be the key to preventing diabetes.

All living things that are sensitive to light—from tiny algae to humans—have built-in clocks that help them keep track of time. These internal clocks, called circadian clocks, help organize many important body processes to follow a daily 24-hour cycle. This includes metabolism: how our bodies manage energy, sugar, and fat.

Disruptions to these natural rhythms—such as irregular sleep, late-night eating, or shift work—can throw our body clocks out of sync. Growing evidence shows that this circadian misalignment may contribute to health problems like obesity, type 2 diabetes, and even cancer.

Understanding how our biological clocks work in different parts of the body—especially the organs involved in metabolism—may help us prevent and treat these diseases more effectively.

RESEARCH AIMS

At our lab, we study how biological clocks function in pancreas, muscle, fat, and gut tissues, and how these clocks are affected by conditions like obesity, diabetes, and cancer. We focus on both rodent models and human cells and tissues.

Specifically, we aim to:

• Explore the molecular clocks in pancreatic α- and β-cells, which produce hormones like insulin and glucagon that control blood sugar. We study how glucose levels affect these clocks and how they function differently in diabetes.
• Examine circadian rhythms in human muscle and fat cells, looking at how these clocks change in healthy conditions versus insulin-resistant states (a key feature of type 2 diabetes).
• Investigate intestinal cell clocks using 3D organoid models to better understand how gut hormones, like GLP-1, are regulated by circadian timing.
• Study the role of circadian clocks in cancer, including thyroid, parathyroid, and lung cancers. We examine whether disrupted clocks contribute to cancer development and how circadian timing might improve cancer diagnosis or treatment.

• Our goal is to uncover how the body’s internal timing system supports health and how restoring proper timing could offer new paths for treating metabolic diseases and cancer.

CORE EXPERTISE

To answer these questions, we use a wide range of cutting-edge methods, including:

• Primary cell cultures with bioluminescence monitoring to track circadian rhythms in real time
• Tandem bioluminescence–fluorescence imaging at both single-cell and population levels
• Multi-omic data analysis to understand clock-regulated gene, protein, and metabolic networks
• Human cohort studies examining how timing of food and day-light affect metabolism
• Rodent and human models to study circadian regulation in physiology and metabolic disease

Together, our research aims to bring precision timing into the prevention and treatment of metabolic and endocrine diseases.

PUBLICATIONS

Here are five selected publications from our team, highlighting recent discoveries at the intersection of circadian biology and metabolic health:

1. Type 2 diabetes disrupts circadian orchestration of lipid metabolism and membrane fluidity in human pancreatic islets
   Volodymyr Petrenko, Flore Sinturel, Ursula Loizides-Mangold, Jonathan Paz Montoya, Simona Chera, Howard Riezman, Charna Dibner
   PLoS Biology, 2022 | Read here
2. Circadian organization of the lipid landscape is perturbed in type 2 diabetic patients
   Flore Sinturel, Simona Chera, Marie-Claude Brulhart-Meynet, Jonathan Paz Montoya, Dirk Jan Stenvers, Peter H. Bisschop, Andries Kalsbeek, Idris Guessous, François R. Jornayvaz, Jacques Philippe, Steven A. Brown, Giovanni D’Angelo, Howard Riezman, Charna Dibner
   Cell Reports Medicine, 2023 | Read here
3. Lipid metabolism around the body clocks
   Volodymyr Petrenko, Flore Sinturel, Howard Riezman, Charna Dibner
   Progress in Lipid Research, 2023 | Read here
4. Alterations of lipid homeostasis in morbidly obese patients are partly reversed by bariatric surgery
   Flore Sinturel, Simona Chera, Marie-Claude Brulhart-Meynet, Jonathan Paz Montoya, Etienne Lefai, François R. Jornayvaz, Giovanni D’Angelo, Minoa Karin Jung, Zoltan Pataky, Howard Riezman, Charna Dibner
   iScience, 2024 | Read here
5. In pancreatic islets from type 2 diabetes patients, the dampened circadian oscillators lead to reduced insulin and glucagon exocytosis Volodymyr Petrenko, Nikhil R. Gandasi, Daniel Sage, Anders Tengholm, Sebastian Barg, Charna Dibner
   Proc Natl Acad Sci. 2020 | Read here

Chronobiology and Personalised Management of Diabetes and Nutrition