Dimitris G. Placantonakis, MD, PhD

 
 
Assistant Professor of Neurosurgery
Director, Neurosurgical Laboratory for Stem Cell Research
MD/PhD, 2003 NYU School of Medicine
Lab address: Alexandria 8th floor, 822F
Office address:
Skirball 8R-303
530 First Avenue
New York, NY 10016
 
Tel: (212) 263-2441 (office)
       (646) 501-2272 (lab)
Research Theme(s): Stem Cell Biology, Glioblastoma/glioma, Human Embryonic Stem Cells, Cancer Stem Cells

Keywords: Stem Cells, Glioblastoma, Glioma, Human Embryonic Stem Cells, Cancer Stem Cells, Gene Therapy
 
Research Title: Stem cell function in glioblastoma and gliomagenesis
 
Research Summary:
 
Our 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 GSCs for the lineages that they generate in vitro and in vivo, molecular markers, metabolic profile and response to treatment. As a result of this effort, we recently identified an adhesion G protein-coupled receptor, GPR133, which is required for glioblastoma growth. We are currently elucidating basic mechanisms of action of GPR133, but also developing it translationally as a novel therapeutic target.
 
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 neomorphic mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) are highly prevalent in low-grade glioma, a slow-growing precursor to glioblastoma. We recently used a human neural stem cell platform to show that tumor initiation by mutant IDH1 is mediated by chromatin conformation changes, which result in reorganization of transcription factor networks that regulate differentiation. We are currently pursuing genetic, biochemical and pharmacologic approaches to elucidate epigenetic changes during glioma initiation and identify novel dependencies of tumor cells.
 
Selected publications:
  • Modrek, A. S., Golub, D., Khan, T., Bready, D., Prado, J., Bowman, C., Deng, J., Zhang, G., Rocha, P., Raviram, R., Lazaris, H., Stafford, J., LeRoy, G., Kader, M., Dhaliwal, J., Bayin, N. S., Frenster, J., Serrano, J., Chiriboga, L., Baitalmal, R., Chi, A., Golfinos, J. G., Wang, J., Karajannis, M., Bonneau, R., Reinberg, D., Tsirigos, A., Snuderl, M., Zagzag, D., Skok, J., Neubert, T., & Placantonakis, D. G. Low-grade astrocytoma mutations in IDH1, P53 and ATRX cooperate to block differentiation of human neural stem cells via repression of SOX2. Cell Reports 2017; 21(5):1267-1280. doi: 10.1016/j.celrep.2017.10.009.
  • Bayin, N.S., Frenster, J.D., Sen, R., Si, S., Modrek, A. S., Galifianakis, N., Dolgalev, I., Ortenzi, V., Illa-Bochaca, I., Khahera, A., Serrano, J., Chiriboga, L., Zagzag, D., Golfinos, J.G., Doyle, W., Heguy, A., Chesler, M., Barcellos-Hoff, M.H., Snuderl, M., & Placantonakis, D. G. Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells. Oncotarget 2017; 8:64932-64953. doi: 10.18632/oncotarget.18117.
  • Frenster, J.D., Inocencio, J. F., Xu, Z., Dhaliwal, J., Alghamdi, A., Zagzag, D., Bayin, N.S., & Placantonakis, D.G. GPR133 promotes glioblastoma growth in hypoxia. Neurosurgery 2017; 64(CN_suppl_1):177-181. doi: 10.1093/neuros/nyx227.
  • Pourchet, A., Modrek, A.S., Placantonakis, D.G., Mohr, I., & Wilson, A.C. Modeling HSV-1 latency in human embryonic stem cell-derived neurons. Pathogens 2017; 6(2):24. doi:10.3390/pathogens6020024.
  • Bayin, N.S., Frenster, J.D., Kane, J.R., Rubenstein, J., Modrek, A.S., Baitalmal, R., Dolgalev,I., Rudzenski, K., Snuderl, M., Golfinos, J.G., Doyle, W., Pacione, D., Parker, E.C., Chi, A.S., Heguy, A., MacNeil, D.J., Shohdy, N., Zagzag, D., & Placantonakis, D.G. GPR133 (ADGRD1), an adhesion G protein-coupled receptor, is necessary for glioblastoma growth. Oncogenesis 2016; 5(10):e263. doi:10.1038/oncsis.2016.63.
  • Bayin, N.S., Ma, L., Thomas, C., Baitalmal, R., Sure, A., Fansiwala, K., Bustoros, M., Golfinos, J.G., Pacione, D., Snuderl, M., Zagzag, D., Barcellos-Hoff, M.H., & Placantonakis, D.G. Patient-specific screening using high-grade glioma explants to determine potential radiosensitization by a TGF-β small molecule inhibitor. Neoplasia 2016; 18:795-805.
  • Tyagi, V., Theobald, J., Barger, J., Bustoros, M., Bayin, N.S., Modrek, A.S., Anderer, E., Donahue, B., Fatterpekar, G., & Placantonakis, D.G. Traumatic Brain Injury and Subsequent Glioblastoma Development: Review of the Literature and Case Reports. Surgical Neurology International 2016; 7:78. doi: 10.4103/2152-7806.189296.
  • Basu-Roy, U., Bayin, N. S., Rattanakorn, K., Han, E., Placantonakis, D. G., Mansukhani, A., & Basilico, C. SOX2 Antagonizes the Hippo Pathway to Maintain Stemness in Cancer Cells. Nature Communications 2015; 6:6411.
  • Bayin, N. S., Modrek, A., Dietrich, A., Abel, T., Song, H.-R., Schober, M., Buchholz, C., Chao, M., & Placantonakis, D. G. Selective Lentiviral Gene Delivery into CD133-expressing human Glioblastoma Stem Cells. PLoSOne 2014; 9:e116114.
  • Bayin, N. S., & Placantonakis, D. G. Heterogeneity and Diversity of Cancer Stem Cells in Glioblastoma. International Journal of Stem Cell Research and Therapy 2014; 1:001e.
  • Bayin, N.S., Modrek, A. S. & Placantonakis, D. G. Glioblastoma Stem Cells: Molecular Characteristics and Therapeutic Implications. World Journal of Stem Cells 2014; 6:230-238.
  • Modrek, A. S., Bayin, N.S. & Placantonakis, D. G. Stem cells as the cell of origin in glioma. World Journal of Stem Cells 2014; 6:43-52.