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Schaaf, Gerben

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Gerben Schaaf studied biology at the Utrecht University (graduated cum laude). He received his PhD by elucidating mechanisms of drug-mediated nephrotoxicity at the Faculty of Veterinary Medicine (Utrecht University). During his postdoctoral career he applied the acquired cell biological skills to study the biology of skeletal muscle tumors, rhabdomyosarcomas, at the Academic Medical Center in Amsterdam (The Netherlands). He discovered that the putative tumor suppressor Sprouty1 harbors oncogenic features in rhabdomyosarcomas and can be efficiently targeted to eradicate these tumors.

Based on his work in rhabdomyosarcoma he received a Veni Award (Netherlands Organization for Scientific Research - NWO) to identify tumor stem cells in rhabdomyosarcoma in the lab of Thomas Rando at the Stanford School of Medicine (Dept. of Neurology and Neurological Services, Palo Alto, USA). In this work he found strong parallels in lineage progression between normal and tumor skeletal muscle, which forms the basis of his current work.

Since 2012, this work is part of the Center for Lysosomal and Metabolic and Diseases (CLMZ; Dept of Pediatrics). The CLMZ is a multidisciplinary center combining fundamental and preclinical research and patient care. In our research we focus on Pompe Disease, which is a progressive muscle wasting disease. The exact mechanism behind the loss of muscle function and mass is still unknown. Pompe disease is, when untreated, fatal for infantile patients. Since 2006 Enzyme Replacement Therapy (ERT) is available for Pompe Patients, which is particularly effective in infantile patient. However, ERT is not equally effective for all patients and is extremely expensive. Novel therapies are warranted. To address this need, we are trying to develop a method to expand muscle stem cells that can contribute efficiently to muscle regeneration following transplantation and restore lost muscle. A muscle cell therapy is challenging, as standard culture protocols rapidly induce loss of regenerative potential. The different research lines aim to unravel the mechanism and requirements for maintaining stem cell potential in-vitro. Our aim is to understand why and how cell-based therapies can be safely used to cure patients suffering from a muscle-degenerative disease. Our results cover single-molecule analyses to in-vivo studies.

Keywords

Muscle Stem Cells, Stem cell-based therapies, Muscle-degenerative disease 

Links

http://www.erasmusmc.nl/lysosomale-en-metaboleziekten/?lang=en


References

Schaaf, G., Sage F. et al. (2012). Ex-vivo Expansion of Muscle-Regenerative Cells for the Treatment of Muscle Disorders. J. Stem Cell Res. Ther. 01.

Gerben Schaaf, Mohamed Hamdi, Danny Zwijnenburg, Arjan Lakeman, Dirk Geerts, Rogier Versteeg, and Kool, M. (2010). Silencing of SPRY1 Triggers Complete Regression of Rhabdomyosarcoma Tumors Carrying a Mutated RAS Gene. Cancer Res. 70.

Missiaglia, E., Selfe, J., Hamdi, M., Williamson, D., Schaaf, G., Fang, C., Koster, J., Summersgill, B., Messahel, B., Versteeg, R., et al. (2009). Genomic imbalances in rhabdomyosarcoma cell lines affect expression of genes frequently altered in primary tumors: an approach to identify candidate genes involved in tumor development. Genes Chromosom. Cancer 48, 455–467.

Van Ruissen, F., Schaaf, G.J., Kool, M., Baas, F., and Ruijter, J.M. (2008). Scaling of gene expression data allowing the comparison of different gene expression platforms. Methods Mol. Biol. 387, 169–183.

Schaaf, G.J., van Ruissen, F., van Kampen, A., Kool, M., and Ruijter, J.M. (2008). Statistical comparison of two or more SAGE libraries: one tag at a time. Methods Mol. Biol. 387, 151–168.

Van Ruissen, F., Ruijter, J.M., Schaaf, G.J., Asgharnegad, L., Zwijnenburg, D.A., Kool, M., and Baas, F. (2005). Evaluation of the similarity of gene expression data estimated with SAGE and Affymetrix GeneChips. BMC Genomics 6, 91.

Schaaf, G.J., Ruijter, J.M., van Ruissen, F., Zwijnenburg, D.A., Waaijer, R., Valentijn, L.J., Benit-Deekman, J., van Kampen, A.H., Baas, F., and Kool, M. (2005). Full transcriptome analysis of rhabdomyosarcoma, normal, and fetal skeletal muscle: statistical comparison of multiple SAGE libraries. Faseb J 19, 404–406.