Department: Molecular Genetics, University of Toronto
Lab: Dick Lab
*SCID mouse an important tool
Dr. Dick's research program aims at understanding how stem cells can be manipulated. He is known around the world for his development of an in vivo repopulation assay (ie: in vivo stem cell assay) using the NOD/SCID mouse. 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 a black box of cancer development
Although it is now important worldwide as a tool for blood research, the 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.