Dimitris G. Placantonakis, MD, PhD
Assistant Professor of Neurosurgery
Director, Neurosurgical Laboratory for Stem Cell Research
MD/PhD, 2003 NYU School of Medicine
Stem Cell Biology, Glioblastoma/glioma, Human Embryonic Stem Cells, Human Induced Pluripotent Stem Cells, Neurogenesis, Gene Therapy
Stem cells, Cancer Stem Cells, Glioblastoma, Glioma, Human Embryonic Stem Cells, Gene Therapy
My laboratory studies the regulation of stem cell function in malignant brain tumors. By definition, stem cells possess two fundamental properties: self-renewal, the ability to preserve stemness; and pluri- or multi-potency, the ability to differentiate to different types of progeny. Our group investigates the molecular mechanisms that govern self-renewal and differentiation potential of cancer stem cells in brain tumors, such as gliomas.
A major project in our laboratory aims to identify distinct classes of cancer stem cells in glioblastoma. Glioblastoma is an aggressive form of brain cancer, in which stem-like cells termed glioblastoma stem cells (GSCs) can recapitulate the entire tumor, while remaining resistant to chemotherapy and radiation. To study GSC biology, we obtain primary human GBM tissue from operative specimens, culture it and inject it into the mouse brain to generate tumor xenografts. Using genetic techniques and lentiviral vectors, we interrogate distinct types of human GBM cells for their ability to behave as stem cells and the lineages that they generate in vitro and in vivo. Moreover, we are testing lentivirus-based gene therapy approaches that directly target stem cells for their therapeutic efficacy in our animal model. Our ultimate goal is to translate our findings to the clinic and develop novel therapeutic approaches for glioblastoma.
An additional area of research in my laboratory focuses on understanding the early steps of gliomagenesis. Over the past few years, brain tumor sequencing has indicated that mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) are highly prevalent in gliomas. In the absence of appropriate animal models, we use human embryonic stem cells as a model system to understand whether mutated IDH1 may lead to oncogenic transformation of human neural lineages and glioma initiation. We envision such a model to develop into a resource for basic investigation of oncogenesis in the brain, as well as translational studies related to drug screening and biomarker identification.
- Desbordes, S. C., Placantonakis, D. G., Ciro, A., Socci,, N. D., Lee, G., Djaballah, H. & Studer, L. (2008) High-throughput screening assay for the identification of compounds regulating self-renewal and differentiation in human embryonic stem cells. Cell Stem Cell 2:602-612. PMID: 18522853
- Placantonakis, D. G., Tomishima, M. J., Lafaille, F., Desbordes, S., Jia, F., Socci, N., Viale, A., Lee, H., Harrison, N., Tabar, V. & Studer, L. (2009) BAC transgenesis in human ES cells as a novel tool to define the human neural lineage. Stem Cells 27:521-532. PMID: 19074416
- Placantonakis, D. G., Tomishima, M. J., Lafaille, F., Desbordes, S., Jia, F., Socci, N., Viale, A., Lee, H., Harrison, N., Studer, L. & Tabar, V. (2009) Enriched motor neuron populations derived from BAC-transgenic human embryonic stem cells. Clinical Neurosurgery 56:125-132. PMID: 20214043
- Tokcaer-Keskin, Z. & Placantonakis, D.G. (2012) Genetic identification of human embryonic stem cell-derived neural cell types using bacterial artificial chromosomes. In Stem Cells and Cancer Stem Cells: Therapeutic Applications in Disease and Injury (ed. M.A. Hayat). Springer, New York, NY (in press).