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Diabetes Program

In this program, investigators under the direction of Dr. C. MATHIEU are testing if cells with insulin-producing beta-cell characteristics generated from stem cells have similar qualities as pancreas-derived beta cells.

Diabetes Program

Studies to be done include:

  1. Transplantation of stem cell derived beta cell like cells, with or without promoter selection, in immunodeficient diabetic mice
  2. Determining which trophic effects are elaborated by these cells, focusing on modification of mitochondrial functions and / or NO-cGMP signal transduction
  3. Determine if co-transplantation with fetal pancreas improves engraftment of stem cell derived beta cell like cells
  4. Evaluate the impact of transplantation site on differentiation potential and function of stem cell derived beta cell like cells
  5. Compare the proteome and transcriptome of stem cell derived beta cell like cells with that of primary beta cells

Lab members

Postdoctoral Fellows
  • Conny Gysemans, PhD
  • Hannelie Korf, PhD
  • Lut Overbergh, PhD
Doctoral Students
  • Femke Baeke, MS
  • Wannes D'Hertog, MS
  • Gabriela Ferreira, MS
  • Michael Maris, MS
  • Tatiana Takiishi, MS
Technicians
Mouse Core
  • Jos Laureys
Real Time PCR
  • Wim Cockx
  • Nursen Gol, BS
Proteomics
  • Jos Depovere
Administration
  • Anne Laeremans
  • Evelyne van Etten, Ph.D

Publications

  • Mathieu, C., Laureys, J., Sobis, H., et al (1992). 1,25-Dihydroxyvitamin D3 prevents insulitis in NOD mice. Diabetes 41, 1491-1495
  • Mathieu C Waer M Laureys Mathieu, C., Waer, M., Laureys, J., et al. (1994) Prevention of type I diabetes in NOD mice by 1,25-dihydroxyvitamin D3. Diabetologia 37: 552-558
  • Casteels, K., Waer, M., Laureys, J., et al (1998) Sex difference in resistance to dexamethasoneinduced apoptosis in NOD mice: treatment with 1,25(OH)2D3 restores defect. Diabetes 47:1033- 1037
  • Overbergh, L., Decallonne, B., Waer, M., et al (2000) 1,25-Dihydroxyvitamin D3 induces an autoantigen specific Th1/Th2 immune shift in nonobese diabetic miceimmunized with GAD65 (p524-543). Diabetes. 49:1301-1307
  • Gysemans, C.A., Waer, M., Valckx, D., et al (2000) Early graft failure of xenogeneic islets in NOD mice is accompanied by high levels of interleukin-1 and low levels of transforming growth factorß mRNA in the grafts. Diabetes. 49:1992-1997
  • Mathieu, C. and L. Adorini. (2002) The coming of age of vitamin D3 as an immunomodulator. Trends Mol Med. 8:174-179
  • Van Halteren, A.G., van Etten, E., De Jong, E.C., et al (2002) Redirection of human autoreactive Tcells upon interaction with dendritic cells modulated by TX527, an analog of 1,25- dihydroxyvitamin D3. Diabetes 51:2119-2125
  • Overbergh, L. Decallonne, B., Branisteanu, D.D., et al (2003) Acute shock induced by antigen vaccination in NOD mice. Diabetes 52:335-341
  • Giulietti A, Gysemans C, Stoffels K, et al (2004) Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice. Diabetologia 47(3): 451-462
  • Keymeulen B, Vandemeulebroucke E, Ziegler AG, et al (2005) Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med 352(25):2598-2608
  • Mathieu C, Badenhoop K. (2005) Vitamin D and type 1 diabetes mellitus: state of the art. Trends Endocrinol Metab 16(6):261-266
  • Gysemans CA, Ladriere L, Callewaert H, et al (2005) Disruption of the gamma-interferon signaling pathway at the level of signal transducer and activator of transcription-1 prevents immune destruction of beta cells. Diabetes 54(8):2396-2403
  • D'Hertog, W., Overbergh, L., Lage, K., et al (2007) Proteomic analysis of cytokine-induced dysfunction and death in insulin producing INS-1E cells: new insights into the pathways involved. Mol Cell Proteomics 6(12):2180-2199.
  • Gysemans, C., van Etten, E., Overbergh, et al. (2008) Unaltered diabetes presentation in NOD mice lacking the vitamin D receptor. Diabetes 57: 269-275
  • Huurman, V.A.L., Hilbrands, R., Pinkse, G.G.M., et al. (2008) Cellular islet autoimmunity associates with clinical outcome of islet cell transplantation. PLoS ONE 3: e2435.
  • Bouillon, R., Carmeliet, G., Verlinden, L., et al. (2008) Vitamin D and human health: Lessons from vitamin D receptor null mice. Endocrine Reviews 29(6):726-776
  • Ferreira, G.B., Overbergh, L., van Etten, E., et al.(2008) Protein-induced changes during the maturation process of human dendritic cells: a 2-D DIGE approach. Proteomics-Clin Application 2: 1349-1360