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

Blood. 2015 Jan 28;
Sriskanthadevan S, Jeyaraju DV, Chung TE, Prabha S, Xu W, Skrtic M, Jhas B, Hurren R, Gronda M, Wang X, Jitkova Y, Sukhai MA, Lin FH, Maclean N, Laister R, Goard CA, Mullen PJ, Xie S, Penn LZ, Rogers IM, Dick JE, Minden MD, Schimmer AD
Mol Syst Biol. 2014;10(7):741
Qiao W, Wang W, Laurenti E, Turinsky AL, Wodak SJ, Bader GD, Dick JE, Zandstra PW
Sci Transl Med. 2014 May 28;6(238):238fs23
Dick JE
Nature. 2014 Jun 12;510(7504):268-72
van Galen P, Kreso A, Mbong N, Kent DG, Fitzmaurice T, Chambers JE, Xie S, Laurenti E, Hermans K, Eppert K, Marciniak SJ, Goodall JC, Green AR, Wouters BG, Wienholds E, Dick JE
Cell Stem Cell. 2014 Mar 6;14(3):275-91
Kreso A, Dick JE
Nature. 2014 Feb 20;506(7488):328-33
Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V, Kennedy JA, Schimmer AD, Schuh AC, Yee KW, McLeod JL, Doedens M, Medeiros JJ, Marke R, Kim HJ, Lee K, McPherson JD, Hudson TJ, HALT Pan-Leukemia Gene Panel Consortium, Brown AM, Yousif F,...
Cell Stem Cell. 2014 Jan 2;14(1):94-106
van Galen P, Kreso A, Wienholds E, Laurenti E, Eppert K, Lechman ER, Mbong N, Hermans K, Dobson S, April C, Fan JB, Dick JE
Blood. 2014 Feb 6;123(6):863-74
Dickinson RE, Milne P, Jardine L, Zandi S, Swierczek SI, McGovern N, Cookson S, Ferozepurwalla Z, Langridge A, Pagan S, Gennery A, Heiskanen-Kosma T, Hämäläinen S, Seppänen M, Helbert M, Tholouli E, Gambineri E, Reykdal S, Gottfreðsson M, Thaventhiran...
Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20599-604
Louria-Hayon I, Frelin C, Ruston J, Gish G, Jin J, Kofler MM, Lambert JP, Adissu HA, Milyavsky M, Herrington R, Minden MD, Dick JE, Gingras AC, Iscove NN, Pawson T
Nat Med. 2014 Jan;20(1):29-36
Kreso A, van Galen P, Pedley NM, Lima-Fernandes E, Frelin C, Davis T, Cao L, Baiazitov R, Du W, Sydorenko N, Moon YC, Gibson L, Wang Y, Leung C, Iscove NN, Arrowsmith CH, Szentgyorgyi E, Gallinger S, Dick JE, O'Brien CA

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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