John E Dick, PhD, FRS

  • SCID mouse model development
    Dr. Dick's research program aims to understand how stem cells can be manipulated. He is known around the world for his development of an in vivo repopulation assay (i.e., in vivo stem cell assay) using the NOD/SCID mouse. Hematopoietic stem cells (HSCs) are found in the bone marrow and are pluripotent: they give rise to all the cellular elements of the blood. Until the development of this model, studies of the human hematopoietic system and diseases of the blood were limited because there was no method to study the development of the human blood system. This model has transformed the study of both normal and leukemic human blood systems.

    The assay involves reconstituting immune deficient SCID mice with either normal human bone marrow or cord blood, or with cells from patients with genetic deficiencies or leukemia. The mouse, being immune deficient, cannot reject the human cells, and thus the human cells readily proliferate and differentiate, generating human hematopoietic cells of erythroid, lymphoid and myeloid lineage in the mouse.
  • Inside the black box of cancer development
    Although it is now important worldwide as a tool for blood research, the SCID mouse model was initially developed to understand and define both normal and leukemic stem cells. In acute myeloid leukemia, only leukemic stem cells can initiate the disease and we have little understanding of which normal cells become transformed in the initiation of leukemia. That is why it is important to characterize the developmental programs of both cell types. Without an understanding of how they are different, the mechanism by which the leukemic process alters the development of the normal blood system will never be understood. Effective anti-leukemia therapy must target the leukemic stem cell to completely eradicate the disease.

    Using the mouse model, it is possible to identify and characterize the leukemic stem cell and determine where it comes from. Until now, this process has always been a mystery. With this model, we will now be able to see inside that black box, and gain a more complete understanding regarding how the molecular pathways differ in normal and leukemic blood systems. Then we will be able to devise therapies to disrupt the molecular process that leads to leukemia and hopefully prevent it from occurring.

Related Links

Cell Rep. 2018 Oct 30;25(5):1109-1117.e5
van Galen P, Mbong N, Kreso A, Schoof EM, Wagenblast E, Ng SWK, Krivdova G, Jin L, Nakauchi H, Dick JE
Exp Hematol. 2018 Oct 20;:
Luciani GM, Xie L, Dilworth D, Tierens A, Moskovitz Y, Murison A, Szewczyk MM, Mitchell A, Lupien M, Shlush L, Dick JE, Arrowsmith CH, Barsyte-Lovejoy D, Minden MD
Blood. 2018 Sep 24;:
Kennedy JA, Madeiros JJF, Dobson SM, Arruda A, Sukhai MA, Stockley T, Tierens A, Minden MD, Kamel-Reid S, Dick JE, Gupta V
Cell Stem Cell. 2018 Aug 21;:
Golan K, Kumari A, Kollet O, Khatib-Massalha E, Subramaniam MD, Ferreira ZS, Avemaria F, Rzeszotek S, García-García A, Xie S, Flores-Figueroa E, Gur-Cohen S, Itkin T, Ludin-Tal A, Massalha H, Bernshtein B, Ciechanowicz AK, Brandis A, Mehlman T,...
Leukemia. 2018 Aug 08;:
Duployez N, Marceau-Renaut A, Villenet C, Petit A, Rousseau A, Ng SWK, Paquet A, Gonzales F, Barthélémy A, Leprêtre F, Pottier N, Nelken B, Michel G, Baruchel A, Bertrand Y, Leverger G, Lapillonne H, Figeac M, Dick JE, Wang JCY, Preudhomme C, Cheok M
Nature. 2018 Jul 09;:
Abelson S, Collord G, Ng SWK, Weissbrod O, Mendelson Cohen N, Niemeyer E, Barda N, Zuzarte PC, Heisler L, Sundaravadanam Y, Luben R, Hayat S, Wang TT, Zhao Z, Cirlan I, Pugh TJ, Soave D, Ng K, Latimer C, Hardy C, Raine K, Jones D, Hoult D, Britten A,...
Nature. 2018 May 16;:
Bahr C, von Paleske L, Uslu VV, Remeseiro S, Takayama N, Ng SW, Murison A, Langenfeld K, Petretich M, Scognamiglio R, Zeisberger P, Benk AS, Amit I, Zandstra PW, Lupien M, Dick JE, Trumpp A, Spitz F
Nature. 2018 Jan 17;:
Bahr C, von Paleske L, Uslu VV, Remeseiro S, Takayama N, Ng SW, Murison A, Langenfeld K, Petretich M, Scognamiglio R, Zeisberger P, Benk AS, Amit I, Zandstra PW, Lupien M, Dick JE, Trumpp A, Spitz F
Sci Transl Med. 2017 Dec 20;9(421):
Wang W, Fujii H, Kim HJ, Hermans K, Usenko T, Xie S, Luo ZJ, Ma J, Celso CL, Dick JE, Schroeder T, Krueger J, Wall D, Egeler RM, Zandstra PW
Clin Cancer Res. 2017 Oct 26;:
Lee JB, Minden MD, Chen WC, Streck E, Chen B, Kang H, Arruda A, Ly D, Der SD, Kang S, Achita P, D'Souza C, Li Y, Childs RW, Dick JE, Zhang L

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Professor, Department of Molecular Genetics, University of Toronto
Director, Program in Cancer Stem Cells, Ontario Institute for Cancer Research (OICR)
Canada Research Chair in Stem Cell Biology