
Patrick COLLOMBAT
Diabetes Genetics
Main interests
- Diabetes
- Regeneration
- Pancreas
- Mouse development
Scientific Questions

The pancreas can be subdivided into two distinct structures: the exocrine and the endocrine tissues. The exocrine compartment secretes and transports digestive enzymes to the duodenum, whereas the endocrine tissue is organized into small clusters of cells termed islets of Langerhans. The latter contain four main different hormone-secreting cell subtypes: alpha-, beta-, delta-, and PP-cells producing glucagon, insulin, somatostatin, and pancreatic polypeptide (PP), respectively.
Both type I and type II diabetes conditions may ultimately result in pancreatic beta-cell loss and chronic hyperglycemia. While current therapies (insulin supplementation, transplantation) provide a measure of control of the glycemia, treated diabetic patients still display a shortened life expectancy and worsened quality of life as compared to their healthy counterparts.
Our research therefore aims at finding alternative ways to treat type 1 diabetes through the induction of beta-cell regeneration.
Our Strategy

Using the mouse as a model, we have initially focused our research on the Arx and Pax4 transcription factors. Importantly, we demonstrated that :
- both factors control endocrine cell development during pancreas morphogenesis, Arx inducing the alpha-cell lineage, whereas Pax4 promotes the beta- and delta-cell fates.
- the forced expression of the Arx gene in adult beta-cells convert these into cells displaying an alpha- or PP-cell phenotype in vivo.
- the misexpression of Pax4 gene in embryonic (Collombat et al., Cell, 2009) or adult alpha-cells induces their continued regeneration and conversion into beta-like cells, such cells being able to reverse several rounds of chemically-induced diabetes in vivo.
Importantly, through a collaborative screening effort, we recently identified several chemical compounds of interest for diabetes research (Ben-Othman et al, Cell, 2017 - Li et al, Cell, 2017). Among these, GABA (γ-aminobutyric acid - a well know neurotransmitter also produced in the pancreas) was found able to induce alpha-cell-mediated beta-like cell neogenesis. Indeed, when provided to animals rendered diabetics, GABA could literally induce the regeneration of a functional beta-cell mass and thereby reverse the consequences of diabetes (multiple times) in vivo.
We are currently deciphering the genetic cascade underlying GABA signalling and running a pilot clinical trial aiming to determine whether GABA could potentially help diabetic patients.
Research Aims

On main focus is to establish ways to induce pancreatic beta-cell regeneration in the context of diabetes research. We have obtained very promising results with the discovery of GABA but we have addional candidates to test. In addition, we work hard in order to understand how GABA works and whether its activities could be potentiated and/or improved.

Using different mouse models combined to human islet studies, we are caracterising the consequences of genetic manipulations of a number of genes on type 1 and type 2 diabetes onset. We have several gene candidates that, when manipulated, could be benificial for both types of diabetes.

Type 1 diabetes is an autoimmune disease targeting insulin-producing beta-cells. Finding ways to regenerate beta-cells is of crucial interest. However, we also need to consider their putative subsequent ablation by the immune system. We are therefore developing approaches allowing their protection from autoimmune attack.
Researchers
NAPOLITANO Tiziana - +33 489150716
SILVANO Serena - +33 489150716
AYACHI Chaïma - +33 489150716
TREINS Caroline - +33 489150717
Engineers & Technicians
VERISSIMO FOFO Hugo Miguel - +33 489150716
ETASSE Laura - +33 489150716
MONGIS Aline - +33 R
MONGIS Aline - +33 R
2024 - Prix des inventeurs 2024, magazine Le Point
2015 - Prix Auguste Loubatière, Société Francophone du Diabète
2014 - Prix G. B. Morgagni
2013 - Apollinaire Bouchardat Award
2013 - Grand Prix de la Fondation Générale de Santé, Académie des Sciences
2011 - ERC Starting Grant
2009 - Schlumberger Prize
2009 - Avenir Excellency, Inserm
2009 - Career Development Award, JDRF
iBV - Institut de Biologie Valrose
"Centre de Biochimie"
Université Nice Sophia Antipolis
Faculté des Sciences
Parc Valrose
06108 Nice cedex 2