Fumiko Shimizu, PhD

Fumiko Shimizu, PhD

Fumiko Shimizu, PhD

Lab Phone

+1 (646) 888-2216

I am developing a diagnostics tool for HSP90 therapy based on next-generation sequencing (NGS) technology using bioinformatic tools and machine learning algorithms. Patient selection for HSP90 therapy in the clinic has been largely driven by the presence of individual “client proteins” (e.g. HER2, mutant ALK) driving the tumor growth. While useful in a subset of tumors, however, such strategy has proven to be insufficient. Many years of studies in the Chiosis lab has recently led to the discovery of the “epichaperome” network (Moulick et al 2011, Rodina et at 2016), which incorporates HSP90 as a key nucleating protein, and is an additional dimension for the mechanism by which HSP90 facilitates oncogene addiction in cancer cells. The epichaperome was present in over half of the cancers tested, and can be dismantled/induced by knock-down/over-expression of transcrition factor Myc. This suggests that the “re-wiring” of the chaperon machinery is supported/induced via a transcription program.

In addition, in collaboration with my colleagues in the Chiosis lab and Dr. Viviane Tabar at the Department of Neurosurgery, I am conducting exploratory studies towards the validation of a PET-based, non-invasive, brain-targeted diagnostic for HSP90 epichaperomes using a human glioblastoma multiform (GBM) mouse xenograft model. Prior to joining the Chiosis lab, I have developed a novel three-dimensional organotypic “explant” system of surgical GBM specimens, that preserve not only the tumor cells, but also the cytoarchitecture and tumor stroma (Shimizu et al 2011). Using this system, I have observed that HSP90 inhibitors can target the glioma stem-like cells as well as the tumor endothelium.


Selected Publications

  1. Rodina, A.*; Wang, T.*; Yan, P.*; Gomes, E. D.*; Dunphy, M. P.*; Pillarsetty, N.; Koren, J.; Gerecitano, J. F.; Taldone, T.; Zong, H.; Caldas-Lopes, E.; Alpaugh, M.; Corben, A.; Riolo, M.; Beattie, B.; Pressl, C.; Peter, R. I.; Xu, C.; Trondl, R.; Patel, H. J.; Shimizu, F.; Bolaender, A.; Yang, C.; Panchal, P.; Farooq, M. F.; Kishinevsky, S.; Modi, S.; Lin, O.; Chu, F.; Patil, S.; Erdjument-Bromage, H.; Zanzonico, P.; Hudis, C.; Studer, L.; Roboz, G. J.; Cesarman, E.; Cerchietti, L.; Levine, R.; Melnick, A.; Larson, S. M.; Lewis, J. S.; Guzman, M. L.; Chiosis, G., The epichaperome is an integrated chaperome network that facilitates tumour survival. Nature 2016, 538 (7625), 397-401.
  2. Xu, R.*; Shimizu, F.*; Hovinga, K.; Beal, K.; Karimi, S.; Droms, L.; Peck, K. K.; Gutin, P.; Iorgulescu, J. B.; Kaley, T.; DeAngelis, L.; Pentsova, E.; Nolan, C.; Grommes, C.; Chan, T.; Bobrow, D.; Hormigo, A.; Cross, J. R.; Wu, N.; Takebe, N.; Panageas, K.; Ivy, P.; Supko, J. G.; Tabar, V.; Omuro, A., Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial. Clinical cancer research : an official journal of the American Association for Cancer Research 2016, 22 (19), 4786-4796.
  3. Cook, P. J.; Thomas, R.; Kingsley, P. J.; Shimizu, F.; Montrose, D. C.; Marnett, L. J.; Tabar, V. S.; Dannenberg, A. J.; Benezra, R., Cox-2-derived PGE2 induces Id1-dependent radiation resistance and self-renewal in experimental glioblastoma. Neuro-oncology 2016, 18 (10), 1379-89.
  4. Shimizu, F.; Hovinga, K. E.; Metzner, M.; Soulet, D.; Tabar, V., Organotypic explant culture of glioblastoma multiforme and subsequent single-cell suspension. Current protocols in stem cell biology 2011, Chapter 3, Unit3.5.
  5. Hovinga, K. E.; Shimizu, F.; Wang, R.; Panagiotakos, G.; Van Der Heijden, M.; Moayedpardazi, H.; Correia, A. S.; Soulet, D.; Major, T.; Menon, J.; Tabar, V., Inhibition of notch signaling in glioblastoma targets cancer stem cells via an endothelial cell intermediate. Stem cells (Dayton, Ohi) 2010, 28 (6), 1019-29.
  6. Lee, G.; Papapetrou, E. P.; Kim, H.; Chambers, S. M.; Tomishima, M. J.; Fasano, C. A.; Ganat, Y. M.; Menon, J.; Shimizu, F.; Viale, A.; Tabar, V.; Sadelain, M.; Studer, L., Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature 2009, 461 (7262), 402-6.
  7. Tahiliani, M.*; Mei, P.*; Fang, R.; Leonor, T.; Rutenberg, M.; Shimizu, F.; Li, J.; Rao, A.; Shi, Y., The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation. Nature 2007, 447 (7144), 601-5.
  8. Shimizu, F.; Fukada, Y., Circadian phosphorylation of ATF-2, a potential activator of Period2 gene transcription in the chick pineal gland. Journal of neurochemistry 2007, 103 (5), 1834-42.
  9. Shimizu, F.; Sanada, K.; Fukada, Y., Purification and immunohistochemical analysis of calcium-binding proteins expressed in the chick pineal gland. Journal of pineal research 2003,34 (3), 208-16.
  10. Hayashi, Y.; Sanada, K.; Hirota, T.; Shimizu, F.; Fukada, Y., p38 mitogen-activated protein kinase regulates oscillation of chick pineal circadian clock. The Journal of biological chemistry 2003, 278 (27), 25166-71.