Raphael Scharfmann, Ph.D. - Investigator Profile
Type-1 diabetes is caused by an autoimmune destruction of insulin producing beta cells resulting in insulin deficiency. Insulin therapy is unsatisfactory since it does not prevent complications associated to type-1 diabetes. Thus defining new strategies (cell or regenerative therapies) as basis to cure diabetic patients represents a major challenge. Beta cells develop from pancreatic progenitors that proliferate and next differentiate into functional insulin-producing cells. This is a complex process, each step being controlled by specific signals. Theoretically, beta cell mass can be enhanced by: i) activating the proliferation of pancreatic progenitors; ii) activating their differentiation into beta cells; iii) activating the proliferation of beta cells themselves. During the past years, we developed tools based on rodent models to search for signals controlling each step of beta cell development. We also developed strategies to transfer to reconstituted human models, data generated in rodent models. We generated new results and hypotheses concerning signals controlling each step of pancreatic development. We also dissected specific forms of neonatal diabetes in Human, which permits to define new treatments for children with neonatal diabetes.
Scientific Interests/Keywords
Pancreas, beta cells, diabetes, development
Publications
| Publication | Citation |
|---|---|
| 20009089 | Heinis M, Simon MT, Ilc K, Mazure NM, Pouysségur J, Scharfmann R, Duvillié B Oxygen tension regulates pancreatic beta-cell differentiation through hypoxia-inducible factor 1alpha. (2010) Diabetes 59: 662-9 (Added 2012-01-24 14:36:04.809475) |
| 19586915 | Filhoulaud G, Guillemain G, Scharfmann R The hexosamine biosynthesis pathway is essential for pancreatic beta cell development. (2009) J Biol Chem 284: 24583-94 (Added 2010-08-03 02:37:34.083816) |
| 19266046 | Ravassard P, Emilie Bricout-Neveu , Hazhouz Y, Pechberty S, Mallet J, Czernichow P, Scharfmann R A new strategy to generate functional insulin-producing cell lines by somatic gene transfer into pancreatic progenitors. (2009) PLoS One 4: e4731 (Added 2012-01-17 15:18:12.138297) |
| 19197155 | Haumaitre C, Lenoir O, Scharfmann R Directing cell differentiation with small-molecule histone deacetylase inhibitors: the example of promoting pancreatic endocrine cells. (2009) Cell Cycle 8: 536-44 (Added 2010-08-03 02:37:34.091718) |
| 18958289 | Scharfmann R, Xiao X, Heimberg H, Mallet J, Ravassard P Beta cells within single human islets originate from multiple progenitors. (2008) PLoS One 3: e3559 (Added 2013-02-15 15:36:19.950126) |
| 18710955 | Haumaitre C, Lenoir O, Scharfmann R Histone deacetylase inhibitors modify pancreatic cell fate determination and amplify endocrine progenitors. (2008) Mol Cell Biol 28: 6373-83 (Added 2012-01-24 14:35:32.383474) |
| 18243096 | Xu X, D'Hoker J, Stangé G, Bonné S, De Leu N, Xiao X, Van de Casteele M, Mellitzer G, Ling Z, Pipeleers D, Bouwens L, Scharfmann R, Gradwohl G, Heimberg H Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas. (2008) Cell 132: 197-207 (Added 2013-02-15 15:36:36.946741) |
| 17376780 | Guillemain G, Filhoulaud G, Da Silva-Xavier G, Rutter GA, Scharfmann R Glucose is necessary for embryonic pancreatic endocrine cell differentiation. (2007) J Biol Chem 282: 15228-37 (Added 2010-08-03 02:38:46.777415) |
| 17322477 | Attali M, Stetsyuk V, Basmaciogullari A, Aiello V, Zanta-Boussif MA, Duvillie B, Scharfmann R Control of beta-cell differentiation by the pancreatic mesenchyme. (2007) Diabetes 56: 1248-58 (Added 2010-08-03 02:38:46.78201) |
| 16885549 | Babenko AP, Polak M, Cavé H, Busiah K, Czernichow P, Scharfmann R, Bryan J, Aguilar-Bryan L, Vaxillaire M, Froguel P Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. (2006) N Engl J Med 355: 456-66 (Added 2010-08-03 02:38:46.786006) |
| 16505219 | Duvillié B, Attali M, Bounacer A, Ravassard P, Basmaciogullari A, Scharfmann R The mesenchyme controls the timing of pancreatic beta-cell differentiation. (2006) Diabetes 55: 582-9 (Added 2012-01-17 15:19:10.709866) |
| 16134081 | Castaing M, Duvillié B, Quemeneur E, Basmaciogullari A, Scharfmann R Ex vivo analysis of acinar and endocrine cell development in the human embryonic pancreas. (2005) Dev Dyn 234: 339-45 (Added 2010-08-03 02:38:46.793772) |
