Research Report 2010 - MDC

Graduate StudentsJoanna SchneiderSina GloyManager of sponsored programsSusanne WisslerTechnical AssistantsStephanie MeyerAnne SchulzeAntje DrägerHundreds of myoblasts can be generated from a single human musclefiber. Mouse anti-human desmin ab (green) and Hoechst stain.mechanism of progressive muscle weakness andreplacement of muscle by connective tissue is still notwell understood. Today, we have increasing evidencethat important aspects of muscular dystrophies mayindeed be endocrinological. In an interdisciplinaryapproach involving pharmacologists, biochemists,endocrinologists and neurologists we investigate glucoseand lipid metabolism in vivo and in vitro in molecularlydefined groups of patients. Some muscular dystrophies,Dunnigan’s for example, feature partial lipodystrophy,early onset of type 2 diabetes mellitus, andnon-alcoholic steatosis. The Spuler group is workingtogether with other ECRC investigators belonging toCRG 192 to elucidate the faulty metabolism of thesedisorders. Joanna Schneider is working on FRET analysisusing glucose sensitive vectors.After muscle injury, muscle satellite cells have the fullpotential to proliferate, differentiate, and conductrepair. However, in tissue culture these cells rapidly losethese properties. Because satellite cells would be agood target for gene therapy, it is important to investigatetheir regenerative potential in vitro. Much informationis available from mouse models. Human satellitecells have not been characterized in any meaningfuldetail. Dr. Stephanie Adams and Sina Gloy isolate andcharacterize human satellite cells. They are focusing inparticular on Notch and Wnt signaling pathways. Thepotential of this work is particularly relevant for theECRC with the advent of the GMP stem cell laboratory,a core facility for all disciplines at the ECRC and MDC.When the time comes, the movement to translate newfindings will be rapid.Selected publicationsSpuler S, Kalbhenn T, Zabojszcza J, van Landeghem FK, Ludtke A, Wenzel K,Koehnlein M, Schuelke M, Lüdemann L, Schmidt HH. Muscle and nervepathology in Dunnigan familial partial lipodystrophy. Neurology. 2007Feb 27;68(9):677-83.Spuler S, Carl M, Zabojszcza J, Straub V, Bushby K, Moore SA, Bähring S,Wenzel K, Vinkemeier U, Rocken C. Dysferlin-deficient muscular dystrophyfeatures amyloidosis. Ann Neurol. 2008 Mar;63(3):323-8.Schmidt S, Vieweger A, Obst M, Mueller S, Gross V, Gutberlet M,Steinbrink J, Taubert S, Misselwitz B, Luedemann L, Spuler S. Dysferlindeficientmuscular dystrophy: gadofluorine M suitability at MR imagingin a mouse model. Radiology. 2009 Jan;250(1):87-94.Knoblauch H, Geier C, Adams S, Budde B, Rudolph A, Schulz-Menger J,Spuler A, Ben Yaou R, Nürnberg P, Voit T, Bonne G, Spuler S. Emery-Dreifuss syndrome in a novel FHL1 mutation. Ann. Neurol. 2009 (in press)Gueneau L, Bertrand AT, Jais JP, Salih MA, Stojkovic T, Wehnert M,Hoeltzenbein M, Spuler S, Knoblauch H, Saitoh S, Verschueren A,Tranchant C, Beuvin M, Lacene E, Romero NB, Heath S, Zelenika D, Voit T,Eymard, Ben Yaou R, Bonne G. Mutations of FHL1 gene cause Emery-Dreifuss muscular dystrophy. Am J Hum Genet 2009 (in press)The Experimental and Clinical Research Center 209