Pax4 overexpression in alpha cells in the pancreas leads insulin production regeneration
Patrick Collombat and his research group are studying type I diabetes, an auto-immune disease characterized by the loss of insulin producing cells in the pancreas (the beta cells). Using mice as a model system, they recently demonstrated that ectopic expression of a single gene (Pax4) in neighboring cells of the pancreas (alpha cells) can induce their regeneration and conversion into insulin producing cells. Cells generated this way are functional and can literally cure a chemically induced diabetes.
Type-I diabetes affects more than 30 million patients worldwide. It is an auto-immune disease affecting the pancreas. The pancreas is an abdominal gland located behind the stomach and connected to the duodenum. This gland contains two types of tissue. On one hand, the exocrine tissue is composed of acinar cells, producing digestive enzymes (like proteases, lipases and nucleases) which are transported through pancreatic ducts (composed of ductal cells) and then discharged into the intestine. On the other hand, the endocrine tissue, which functional unit is the Langerhans islet, is composed, in mice, of a core of beta cells surrounded by alpha, delta and PP cells. Those cells secrete respectively insulin, glucagon, somatostatin and the pancreatic peptide. Insulin and glucagon are involved in glucidic homeostasis: the first one is hypoglycemic and secreted in response to a sugar intake whereas the second one is hyperglycemic and secreted in case of fasting or physical effort.
Patrick Collombat’s research is particularly focused on type I diabetes, which is characterized by the loss of beta cells in the pancreas (the ones producing insulin). Using mice as a model system, he and his team recently showed that ectopic expression of Pax4 in alpha cells of the pancreas were able to induce a beta cells regeneration, and their conversion into insulin producing cells. It is interesting to note that cells generated this way are functional and can literally cure a chemically induced diabetes.
Patrick Collombat’s work is currently focused on chemically inducing Pax4 with the hope of developing a human application. With other laboratories, they set up several screens and managed to find a compound allowing the activation of Pax4 and the regeneration of insulin producing cells. Patrick Collombat is trying with his team to decipher the molecular mecanisms involved and to determine whereas other compounds might have similar activities.
• 1999 : M. Sc., University Toulouse III, France
• 2004 : Ph. D., Max Planck Institute Goettingen, Germany, Ahmed Mansouri's lab
• 2004-2009 : Post-doctoral training, Max Planck Institute Goettingen, Germany, Ahmed Mansouri's lab
• 2009 : appointed research associate (Inserm CR1)
• Chevalier Ordre National du Mérite, 2018
• Auguste Loubatières Prize, 2015
• G. B. Morgagni Silver medal Young Investigator Award, Servier, 2014
• Appolinaire Bouchardat Prize, 2013
• Prize of the French Academy of Science (Fondation Générale de la Santé), 2013
• Starting Grant of the European Research Council (ERC), 2011
• JJDRF Career Development Award, 2010
Co-fondateur et conseiller scientifique de la compagnie DiogenX (sponsorisée par la JDRF USA, Boehringer Ingelheim Venture Fund Allemagne et Advent Biotechnology France) ayant levé 4.5 millions d’euros en 2020
Passage sur France Bleu, April 2017
Interview sur un site de patients, Dec 2016