JOHN DICK’S LABORATORY
Congratulations. Our lab have been selected as the 2013 recipient of the Lap-Chee Tsui Publication Award (biomedical research) for our publication “Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer, Science 2013; 339 (6119): 543-548”.
Dominant-negative Ikaros cooperates with BCR-ABL1 to induce human acute myeloid leukemia in xenografts. [Jan, 2015] Historically, our understanding of mechanisms underlying human leukemogenesis are inferred from genetically engineered mouse models. Relatively, few models that use primary human cells recapitulate the full leukemic transformation as assayed in xenografts and myeloid transformation is infrequent. Full story can be view in pubmed abstract.
The unfolded protein response governs integrity of the haematopoietic stem-cell pool during stress. [Jun, 2014] The blood system is sustained by a pool of haematopoietic stem cells (HSCs) that are long-lived due to their capacity for self-renewal. A consequence of longevity is exposure to stress stimuli including reactive oxygen species (ROS), nutrient fluctuation and DNA damage. Damage that occurs within stressed HSCs must be tightly controlled to prevent either loss of function or the clonal persistence of oncogenic mutations that increase the risk of leukaemogenesis. Full story can be view in pubmed abstract.
Reduced lymphoid lineage priming promotes human hematopoietic stem cell expansion. [Jan, 2014] The hematopoietic system sustains regeneration throughout life by balancing self-renewal and differentiation. To stay poised for mature blood production, hematopoietic stem cells (HSCs) maintain low-level expression of lineage-associated genes, a process termed lineage priming. Here, we modulated expression levels of Inhibitor of DNA binding (ID) proteins to ask whether lineage priming affects self-renewal of human HSCs. We found that lentiviral overexpression of ID proteins in cord blood HSCs biases myeloerythroid commitment at the expense of lymphoid differentiation. Full story can be view in pubmed abstract.
Self-renewal as a therapeutic target in human colorectal cancer. [Jan, 2014] Tumor recurrence following treatment remains a major clinical challenge. Evidence from xenograft models and human trials indicates selective enrichment of cancer-initiating cells (CICs) in tumors that survive therapy. Together with recent reports showing that CIC gene signatures influence patient survival, these studies predict that targeting self-renewal, the key 'stemness' property unique to CICs, may represent a new paradigm in cancer therapy. Here we demonstrate that tumor formation and, more specifically, human colorectal CIC function are dependent on the canonical self-renewal regulator BMI-1. Full story can be view inpubmed abstract.
Stem Cells: Genome-Wide Study of Genes That Regulate Blood Development [June, 2013] Blood production goes through multiple stages of development starting with hematopoietic stem cells (HSCs) which transition into increasingly more specialized cells—called progenitors—that eventually develop into blood cells. Scientists have been able to identify some of the individual genes that regulate this process in humans; however, a comprehensive examination of the network of genes involved had not been performed…. Full Story and view the pubmed abstract.
Cancer: New Discovery for Tumour Growth [December 17, 2012] A study published in Science by OCI Senior Scientist Dr. John Dick has uncovered new evidence suggesting multiple potential causes of cancer tumour growth. Using an experimental model to study human colorectal cancer, Dr. Dick, alongside Dr. Antonija Kreso, OCI Scientist Dr. Catherine O’Brien and collaborators found that genetic mutations, regarded by many as the chief suspect driving cancer growth, are only one piece of the cancer puzzle. Biological factors and cell behaviour were also found to drive tumour growth, contributing to treatment failure and relapse …. Full Story and view the pubmed abstract.
miRNA126 Controls Hematopoietic Stem Cell Expansion [November 7, 2012] Blood cell production is regulated by the differentiation of multi-potent hematopoietic stem cells (HSC) into specific blood lineages. The outcome of this process is determined by the homeostatic balance between HSC quiescence, proliferation and activation by extrinsic stimuli. Insight into how this balance is maintained may allow researchers to overcome limitations in the ability to amplify HSC populations for research and clinical use. Full Story and view the pubmed abstract.
Advancing Personalized Cancer Therapies [May, 2012] Dr. John Dick was featured in a recent Financial Post article as part of the Princess Margaret Hospital Foundation's "Believe It!" campaign for personalized cancer medicine. Dr. Dick discussed his current research, which aims to develop drug therapy for leukemia that is tailored for specific patients. The project, in collaboration with Dr. Dennis Carson of the University of California, San Diego, will involve the transplantation of leukemia cells from 50 human patients into a mouse model that mimics this disease. The effectiveness of a single anti-cancer drug will be assessed across a spectrum of human leukemia.
Top 10 cancer research breakthroughs of 2011 [February, 2012] Findings published by Dr. John Dick were included on a list released by the Canadian Cancer Society of the top 10 cancer research breakthroughs of 2011. Dr. Dick's team was recognized for their discovery of a hematopoietic stem cell that is capable of repopulating the entire blood system. These findings, published in Science, may relieve the demand for bone marrow for use in transplants, facilitating treatment of leukemia and other blood-related diseases. Learn more about the discovery by accessing the scientific article or read a summary in the July 2011 issue of the McEwen Monthly.
Top downloaded paper in Cell Stem Cell [February 21, 2012] Our publication “Hematopoiesis: A Human Perspective” was the top downloaded paper from Cell Stem Cell for the 30 days preceding today. It reviews 2 decades of studies focusing on isolation and molecular regulation of human HSCs, therapeutic applications, and early lineage commitment steps, and compares mouse and humanized models to identify both conserved and species-specific mechanisms that will aid future preclinical research.
Congratulations to Antonija Kreso [January 19, 2012] who has completed her PhD in the Department of Molecular Genetics, University of Toronto.
Nature and science intersect at the lab retreat [October 6, 2011] Sometimes science can seem like you are going up river without a paddle but not at the lab retreat. We enjoyed a morning of scientific discussion and a kayak up the Humber River.
How it felt to discover the mother of all stem cells for the human blood system [December 23, 2011] John Dick’s discovery is highlighted in Globe and Mail series that collected the stories of people who found themselves at the centre major news events. Find it on slide 10 of the series.
New research validates clinical importance of leukemia stem cells and paves the way for personalized treatment [August 28, 2011] Research published today in Nature Medicine focuses on patients and shows that acute myeloid leukemia (AML) contains rare cells with stem cell properties, called leukemia stem cells (LSC), that are better at predicting clinical outcome than the majority of AML cells, showing for the first time that LSCs are significant not just in experimental models but also in patients. View the pubmed abstract or press release.
Isolation of the Purest Blood Stem Cells [August 9, 2011] Hematopoietic stem cells (HSCs) are solely responsible for lifelong blood production, but they are very rare making them difficult to isolate. In the current study, published in Science and led by Dr. John Dick, researchers identified a method to isolate single HSCs capable of developing into multiple cell types comprising a functional blood system. View the pubmed abstract or press release.
Congratulations to Stephanie Dobson [July 1, 2011] Graduate student Stephanie Dobson has won the Frederick Banting and Charles Best Canada CIHR Masters Award.
Uncovering Genetic Diversity in Propagating Cells [January 20, 2011] Dr. John Dick and collaborators at St. Jude Children’s Research Hospital (Memphis) have found that defective genes and the individual leukemia cells that carry them are organized in a more complex way than previously thought. The findings, published in Nature, challenge the conventional view that cancer progresses as a linear series of genetic events and that all the cells in a tumour share the same genetic abnormalities and growth properties. View the pubmed abstract or press release