Clinical Lecture in Neurosurgery, Department of Clinical Neurosciences
Laboratory for Regenerative Medicine
Mechanisms regulating differentiation of oligodendrocyte precursor cells
• Dr Yasir-Ahmed Syed (Postdoc)
• Dr Ana Amaral (Postdoc)
• Dr Matthias Pawlowski
• Sarah Ali Abdulla (PhD Student)
• Ginez Gonzales (PhD Student)
• Matthias Hofer (PhD Student)
• Kelly Inthanon (Visiting scientist)
My group is interested in the biology of adult CNS stem and precursor cells. We use cellular re-programming techniques to gain insight in the transcriptional and epigenetic events that determine cellular identity. In particular, we are interested in understanding genetic and epigenetic mechanisms that define the cellular states of OPCs, neural stem cells, and fully differentiated neural cell types.
A limited set of transcription factors enables trans-lineage re-programming of somatic cells into distinct neural cell types. Based on this paradigm we:
1) study basic mechanisms controlling cellular identity
2) create patient specific disease models for the study of genetic factors in clinical disease
3) develop cellular platforms that can be used for toxicological investigation.
A second focus of our lab lies on mechanisms of CNS remyelination, a stem/precursor cell-mediated process in which new myelin sheaths are restored to demyelinated nerve fibres (axons). To understand how the differentiation of multipotent oligodendrocyte precursor cells (OPCs) is regulated we use a combination of in vitro and in vivo models. Furthermore, we integrate findings of post mortem studies and aim at translating our findings into clinical studies.
Direct cellular reprogramming differs from conventional differentiation in that it is initiated by forced expression / silencing of reprogramming factors and that it is direct and does not entail a stepwise progression of known precur- sor stages to reach the targeted cell population.
Kotter MR, Stadelmann C, Hartung H, Enhancing CNS remyelination in disease – can we wrap it up? Brain 2010: In Press.
Syed YA, Hand E, Möbius M, Zhao C, Hofer M, Nave KA, Kotter MR, Inhibition of CNS remyelination by the presence of Semaphorin 3A, J Neurosci, 2010: In Press.
Syed YA, Vig R, Hoeger H, ffrench-Constant C, Franklin RJM, Altmann F, Lubec G, Kotter MR, Myelin-mediated inhibition of oligodendrocyte precursor cell differentiation can be overcome by pharmacological modulation of Fyn-RhoA and protein kinase C signalling Baer AS, Brain, 132:465-81, 2009
Kotter MR, Li WW, Zhao C, Franklin RJM, Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation, J Neurosci, 26:328-332, 2006.
Kotter MR, Setzu A, Sim FJ, Van Rooijen N, Franklin RJM, Macrophage depletion impairs oligodendrocyte remyelination following lysolecithin-induced demyelination, Glia, 35:204-212, 2001.
Alexandra S. Baer, Yasir A. Syed, Sung Ung Kang, Dieter Mitteregger, Raluca Vig, Charles ffrench-Constant, Robin J. M. Franklin, Friedrich Altmann, Gert Lubec, and Mark R. Kotter Myelin-mediated inhibition of oligodendrocyte precursor differentiation can be overcome by pharmacological modulation of Fyn-RhoA and protein kinase C signalling, Brain, February 2009; 132: 465 – 481.