Genetic and epigenetic regulation of pancreas development

The pancreas is an interesting model recapitulating the fundamental mechanisms of development (differentiation, migration, polarity...), with a medical relevance given the high prevalence of diabetes and pancreatic cancer. 

We study genetic and epigenetic control of pancreas organogenesis and function, using different mouse models allowing analysis of the role of transcription factors and epigenetic factors. We focus on the transcription factor HNF1B and the monogenic diabetes MODY5 (Maturity Onset Diabetes of the Young), as well as histone deacetylases (HDACs), combining phenotypic, physiological, molecular, and whole genome analyzes. 

How:

  • proliferation of pancreatic progenitors
  • generation of endocrine precursors
  • differentiation of endocrine and exocrine cells, are controlled? 

Our goal is to decipher the regulatory networks governing these processes, in correlation with human physiopathology.

More...

Our research focuses on the molecular and cellular mechanisms controlling organogenesis and pancreatic function. The pancreas is a mixed exocrine gland (secretion of digestive enzymes by the acini) and endocrine (secretion of hormones including insulin by the islets of Langerhans), essential for nutrition and glucose homeostasis. It is interesting to study this organ, which is a model recapitulating the fundamental mechanisms of development (lineage differentiation, migration, polarity...). These studies have also a medical relevance given the high prevalence of pancreatic diseases: diabetes and pancreatic cancer. 

We study genetic and epigenetic control of pancreas development and function, using different mouse models allowing analysis of the role of transcription factors and epigenetic factors. We focus on the transcription factor HNF1B and monogenic diabetes MODY5 (Maturity Onset Diabetes of the Young), as well as histone deacetylases (HDACs), combining phenotypic, physiological, molecular, and whole genome analyzes. 

Our goal is to decipher the regulatory networks governing proliferation of pancreatic progenitors, generation of endocrine precursors, differentiation of endocrine and exocrine cells, in relation to human physiopathology.

  • Genetic Mechanisms 

Role of HNF1B in pancreatic progenitors, pancreatic ducts, in endocrine cell generation and islet morphogenesis, and in acinar cell maintenance. Understanding the etiology and pathophysiology of MODY5 diabetes.

  • Epigenetic mechanisms 

Role of Class I HDACs in pancreatic progenitors, endocrine precursor cells and β cells, in the maintenance of acinar cells

Collaborations

  • Dr Maike Sander; University of California, San Diego, USA.
  • Dr Torbjorn Lundstedt; Acurepharma, Umea, Sweden.
  • Dr Eric Olson; Dr Rhonda Bassel-Duby. Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.