Gerard Gradwohl, Ph.D - Investigator Profile
Understanding the mechanisms controlling multipotent stem cells differentiation into specialized cells is one of the current challenges in stem cell biology. Progress in this line of research is critical for the generation of therapeutic cells for cell replacement therapies in diseases such as Type-1 diabetes where insulin-producing beta-cells are destroyed. In this perspective, our goal is to decipher the molecular and cellular mechanisms underlying the differentiation of pancreatic stem/progenitor cells into mature endocrine cells, including beta cells, as well of closely related intestinal cells, both during embryonic development and in the adult life. We focus on the role of signals and transcription factors in the control of cell fate choices and the acquisition of the generic and specific properties of the different endocrine cell types in both organs. We use pancreas explant cultures to screen for novel signaling molecules that would control the induction and expansion of islet progenitor cells and their differentiation in beta cells. Taken together our studies should provide novel insights into the regulation of cellular diversity in the developing pancreas and thus provide new means to generate mature insulin producing cells from embryonic or induced pluripotent stem cells.
Scientific Interests/Keywords
Genetic control of pancreatic and intestinal endocrine cells differentiation
Publications
| Publication | Citation |
|---|---|
| 22056785 | Beucher A, Martín M, Spenle C, Poulet M, Collin C, Gradwohl G Competence of failed endocrine progenitors to give rise to acinar but not ductal cells is restricted to early pancreas development. (2012) Dev Biol 361: 277-85 (Added 2012-03-21 06:47:01.549199) |
| 21947380 | Hald J, Galbo T, Rescan C, Radzikowski L, Sprinkel AE, Heimberg H, Ahnfelt-Rønne J, Jensen J, Scharfmann R, Gradwohl G, Kaestner KH, Stoeckert C, Jensen JN, Madsen OD Pancreatic islet and progenitor cell surface markers with cell sorting potential. (2012) Diabetologia 55: 154-65 (Added 2012-12-19 04:20:18.105766) |
| 21464713 | Mellitzer G, Gradwohl G Enteroendocrine cells and lipid absorption. (2011) Curr Opin Lipidol 22: 171-5 (Added 2012-02-08 02:17:50.79698) |
| 21074524 | Pelling M, Anthwal N, McNay D, Gradwohl G, Leiter AB, Guillemot F, Ang SL Differential requirements for neurogenin 3 in the development of POMC and NPY neurons in the hypothalamus. (2011) Dev Biol 349: 406-16 (Added 2012-02-08 02:18:52.060352) |
| 20364088 | Mellitzer G, Beucher A, Lobstein V, Michel P, Robine S, Kedinger M, Gradwohl G Loss of enteroendocrine cells in mice alters lipid absorption and glucose homeostasis and impairs postnatal survival. (2010) J Clin Invest 120: 1708-21 (Added 2011-03-13 12:45:29.390421) |
| 20040487 | Soyer J, Flasse L, Raffelsberger W, Beucher A, Orvain C, Peers B, Ravassard P, Vermot J, Voz ML, Mellitzer G, Gradwohl G Rfx6 is an Ngn3-dependent winged helix transcription factor required for pancreatic islet cell development. (2010) Development 137: 203-12 (Added 2011-04-19 12:44:37.68382) |
| 18795106 | Quayum N, Kutchma A, Sarkar SA, Juhl K, Gradwohl G, Mellitzer G, Hutton JC, Jensen J GeneSpeed Beta Cell: an online genomics data repository and analysis resource tailored for the islet cell biologist. (2008) Exp Diabetes Res 2008: 312060 (Added 2009-07-15 16:37:29) |
| 18455124 | Petrova TV, Nykänen A, Norrmén C, Ivanov KI, Andersson LC, Haglund C, Puolakkainen P, Wempe F, von Melchner H, Gradwohl G, Vanharanta S, Aaltonen LA, Saharinen J, Gentile M, Clarke A, Taipale J, Oliver G, Alitalo K Transcription factor PROX1 induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype. (2008) Cancer Cell 13: 407-19 (Added 2009-12-27 09:45:18.773668) |
| 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) |
| 17923766 | Martin M, Hauer V, Messmer M, Orvain C, Gradwohl G Transcription factors in pancreatic development. Animal models. (2007) Endocr Dev 12: 24-32 (Added 2008-01-25 10:14:58) |
| 17336910 | Johansson KA, Dursun U, Jordan N, Gu G, Beermann F, Gradwohl G, Grapin-Botton A Temporal control of neurogenin3 activity in pancreas progenitors reveals competence windows for the generation of different endocrine cell types. (2007) Dev Cell 12: 457-65 (Added 2008-01-25 10:15:24) |
| 16511571 | Mellitzer G, Bonne S, Luco RF, Van De Casteele M, Lenne-Samuel N, Collombat P, Mansouri A, Lee J, Lan M, Pipeleers D, Nielsen FC, Ferrer J, Gradwohl G, Heimberg H IA1 is NGN3-dependent and essential for differentiation of the endocrine (2006) EMBO J null: null (Added 2006-03-13 04:09:45) |
| 16026781 | Martin M, Gallego-Llamas J, Ribes V, Kedinger M, Niederreither K, Chambon P, Dolle P, Gradwohl G Dorsal pancreas agenesis in retinoic acid-deficient Raldh2 mutant mice. (2005) Dev Biol 284: 399-411 (Added 2005-09-06 01:31:18) |
| 15668393 | Haumaitre C, Barbacci E, Jenny M, Ott MO, Gradwohl G, Cereghini S Lack of TCF2/vHNF1 in mice leads to pancreas agenesis. (2005) Proc Natl Acad Sci U S A 102: 1490-5 (Added 2005-04-13 12:56:29) |
| 15297605 | Mellitzer G, Martin M, Sidhoum-Jenny M, Orvain C, Barths J, Seymour PA, Sander M, Gradwohl G Pancreatic islet progenitor cells in neurogenin 3-yellow fluorescent (2004) Mol Endocrinol 18: 2765-76 (Added 2005-04-13 12:56:32) |
| 14561778 | Collombat P, Mansouri A, Hecksher-Sorensen J, Serup P, Krull J, Gradwohl G, Gruss P Opposing actions of Arx and Pax4 in endocrine pancreas development. (2003) Genes Dev 17: 2591-603 (Added 2005-04-13 12:56:37) |
| 12829622 | Kaestner KH, Lee CS, Scearce LM, Brestelli JE, Arsenlis A, Le PP, Lantz KA, Crabtree J, Pizarro A, Mazzarelli J, Pinney D, Fischer S, Manduchi E, Stoeckert CJ Jr, Gradwohl G, Clifton SW, Brown JR, Inoue H, Cras-Meneur C, Permutt MA Transcriptional program of the endocrine pancreas in mice and humans. (2003) Diabetes 52: 1604-10 (Added 2005-04-13 12:56:34) |
| 12456641 | Jenny M, Uhl C, Roche C, Duluc I, Guillermin V, Guillemot F, Jensen J, Kedinger M, Gradwohl G Neurogenin3 is differentially required for endocrine cell fate (2002) EMBO J 21: 6338-47 (Added 2005-04-13 12:51:32) |
| 11502253 | Scardigli R, Schuurmans C, Gradwohl G, Guillemot F Crossregulation between Neurogenin2 and pathways specifying neuronal (2001) Neuron 31: 203-17 (Added 2005-04-13 13:02:01) |
| 10825208 | Jacquemin P, Durviaux SM, Jensen J, Godfraind C, Gradwohl G, Guillemot F, Madsen OD, Carmeliet P, Dewerchin M, Collen D, Rousseau GG, Lemaigre FP Transcription factor hepatocyte nuclear factor 6 regulates pancreatic (2000) Mol Cell Biol 20: 4445-54 (Added 2005-04-13 13:01:59) |
| 10821751 | Hojo M, Ohtsuka T, Hashimoto N, Gradwohl G, Guillemot F, Kageyama R Glial cell fate specification modulated by the bHLH gene Hes5 in mouse (2000) Development 127: 2515-22 (Added 2005-04-13 13:02:04) |
| 10677506 | Gradwohl G, Dierich A, LeMeur M, Guillemot F neurogenin3 is required for the development of the four endocrine cell (2000) Proc Natl Acad Sci U S A 97: 1607-11 (Added 2005-04-13 13:08:07) |
