John E Dick, PhD, FRS

Senior Scientist, Princess Margaret Cancer Centre
https://orcid.org/0000-0002-9527-8317
Keywords: leukemia, acute myeloid leukemia (AML), cancer stem cells, stem cells, regenerative medicine, hematopoiesis
  • 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

Lab Website

Canada Research Chair in Stem Cell Biology



Associated Program(s)
Sphingolipid Modulation Activates Proteostasis Programs to Govern Human Hematopoietic Stem Cell Self-Renewal.
Cell Stem Cell. 2019 Oct 11;:
Xie SZ, Garcia-Prat L, Voisin V, Ferrari R, Gan OI, Wagenblast E, Kaufmann KB, Zeng AGX, Takayanagi SI, Patel I, Lee EK, Jargstorf J, Holmes G, Romm G, Pan K, Shoong M, Vedi A, Luberto C, Minden MD, Bader GD, Laurenti E, Dick JE
Functional profiling of single CRISPR/Cas9-edited human long-term hematopoietic stem cells.
Nat Commun. 2019 Oct 18;10(1):4730
Wagenblast E, Azkanaz M, Smith SA, Shakib L, McLeod JL, Krivdova G, Araújo J, Shultz LD, Gan OI, Dick JE, Lechman ER
An ERG Enhancer-Based Reporter Identifies Leukemia Cells with Elevated Leukemogenic Potential Driven by ERG-USP9X Feed-Forward Regulation.
Cancer Res. 2019 Aug 01;79(15):3862-3876
Aqaqe N, Yassin M, Yassin AA, Ershaid N, Katz-Even C, Zipin-Roitman A, Kugler E, Lechman ER, Gan OI, Mitchell A, Dick JE, Izraeli S, Milyavsky M
High efficiency error suppression for accurate detection of low-frequency variants.
Nucleic Acids Res. 2019 May 25;:
Wang TT, Abelson S, Zou J, Li T, Zhao Z, Dick JE, Shlush LI, Pugh TJ, Bratman SV
A stemness screen reveals C3orf54/INKA1 as a promoter of human leukemia stem cell latency.
Blood. 2019 Feb 22;:
Kaufmann KB, Garcia-Prat L, Liu Q, Ng SWK, Takayanagi SI, Mitchell A, Wienholds E, van Galen P, Cumbaa CA, Tsay MJ, Pastrello C, Wagenblast E, Krivdova G, Minden MD, Lechman ER, Zandi S, Jurisica I, Wang JCY, Xie SZ, Dick JE
A novel method for detecting the cellular stemness state in normal and leukemic human hematopoietic cells can predict disease outcome and drug sensitivity.
Leukemia. 2019 Jan 31;:
Yassin M, Aqaqe N, Yassin AA, van Galen P, Kugler E, Bernstein BE, Koren-Michowitz M, Canaani J, Nagler A, Lechman ER, Dick JE, Wienholds E, Izraeli S, Milyavsky M
Integrated Stress Response Activity Marks Stem Cells in Normal Hematopoiesis and Leukemia.
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
Characterization of inv(3) cell line OCI-AML-20 with stroma dependent CD34 expression.
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
Distinct patterns of clonal evolution in patients with concurrent myelo- and lymphoproliferative neoplasms.
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
Daily Onset of Light and Darkness Differentially Controls Hematopoietic Stem Cell Differentiation and Maintenance.
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,...

Pages


 
Senior Scientist, Princess Margaret Cancer Centre

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