Pruszak:Research



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 '''This website is under construction. So is the lab.''' '''The goal of our work is to enhance present knowledge of lineage specification and cell-cell interactions in human neural development. ''' Our current focus is the identification of cell-contact- as well as diffusible factor-mediated determinants of neural lineage specification. We utilize human pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells) as the chief model system, complemented with primary neural cell cultures, tumor cell lines and transgenic mouse model systems. Important techniques include a number of cell and tissue culture-based assays, state-of-the-art molecular and cell biology, flow cytometry and FACS, histological analysis and microscopy. Human pluripotent stem cells (hPSCs) represent a valuable system to study cellular processes and disease mechanisms in phenotypes of biomedical interest and to derive cells and tissues for regenerative medicine and cell therapy. Neural differentiation of human stem cells represents a promising avenue to derive specific neuronal and glial phenotypes for potential cell replacement in the therapy of nervous system disease. Among others, therapies are being investigated for degenerative neurological disorders such as Parkinson’s and Huntington’s disease, for glial disorders such as multiple sclerosis or for trauma conditions such as spinal chord injury. PSCs are, in principle, unlimited in their expansion potential and represent an epigenetically “blank slate” that enables directed patterning toward all lineages. Importantly, the differentiation of human neural cell types from human pluripotent stem cells enables the study of neural development in an understudied model organism to date only remotely accessible to biological discovery: humans. Selected publications:
 * J.E. Carette*, J. Pruszak*, M. Varadarajan, V.A. Blomen, S. Gokhale, F.D. Camargo, M. Wernig, R. Jaenisch, T.R. Brummelkamp: Generation of iPSCs from cultured human malignant cells. Blood 2010 115:4039-42. * equal contribution
 * S. Chung, A. Leung, B.S Han, M.Y. Chang, J.I. Moon, C.H. Kim, S. Hong, J.Pruszak, O. Isacson, K.S. Kim: Wnt1-lmx1a forms a novel autoregulatory loop and controls midbrain dopaminergic differentiation synergistically with the SHH-FoxA2 pathway. Cell Stem Cell 2009 5:646-58.
 * J. Pruszak, W. Ludwig, A. Blak, K. Alavian, O. Isacson: CD15, CD24 and CD29 define a surface biomarker code for neural lineage differentiation of stem cells. Stem Cells 2009 27:2928-40.
 * H. Wakimoto, S. Kesari, C.J. Farrell, W.T. Curry WT, C. Zaupa, M. Aghi, T. Kuroda, A. Stemmer-Rachamimov, K. Shah, T.C. Liu, D.S. Jeyaretna, J. Debasitis, J. Pruszak, R.L. Martuza, S.D. Rabkin: Human glioblastoma-derived cancer stem cells: establishment of invasive glioma models and treatment with oncolytic herpes simplex virus vectors. Cancer Research 2009 69:3472-81.
 * J. Pruszak, O. Isacson: Molecular and cellular determinants for generating ES-cell derived dopamine neurons for cell therapy. Adv Exp Med Biol 2009 651:112-23.
 * M. Wernig, J.P. Zhao*, J. Pruszak*, E. Hedlund, D. Fu, F. Soldner, V. Broccoli, M. Constantine-Paton, O. Isacson, R. Jaenisch: Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. PNAS 2008 105:5856-61. * equal contribution
 * E.M. Hedlund, J. Pruszak, T. Lardaro, W. Ludwig, A. Viñuela, K.S. Kim, O. Isacson: Embryonic stem (ES) cell-derived Pitx3-eGFP midbrain dopamine neurons survive enrichment by FACS and function in an animal model of Parkinson's Disease. Stem Cells 2008 26:1526-36.
 * J. Pruszak, K.C. Sonntag, M.H. Aung, R. Sanchez-Pernaute, O. Isacson: Markers and methods for cell sorting of human embryonic stem cell-derived neural cell populations. Stem Cells 2007 25:2257-68.
 * K.C. Sonntag, J. Pruszak, T. Yoshizaki, J. van Arensbergen, R. Sanchez-Pernaute, O. Isacson: Enhanced yield of neuroepithelial precursors and midbrain-like dopaminergic neurons from human embryonic stem cells using the BMP antagonist noggin. Stem Cells 2007 25:411-8.
 * S. Chung, B.S. Shin, E. Hedlund, J.Pruszak, O. Isacson et al.: Genetic selection of sox1GFP-expressing neural precursors removes residual tumorigenic pluripotent stem cells and attenuates tumor formation after transplantation. J Neurochem 2006 97:1467-80.