John Dick

Summary of Previous Research

• The Development of Xenograft Assays: Dr. Dick pioneered the development of xenograft assays. He created the first system, modelled after clinical transplantation, for transplanting human hematopoietic cells into immune-deficient mice, resulting in multilineage repopulation of murine hematopoietic tissues. Additionally, he established the first xenograft models of human leukemia (B-ALL, AML, CML). This xenograft assay is universally recognized as the "gold standard" for detecting human HSC and LSC and plays a crucial role in evaluating various therapeutics, leading to more effective clinical trials.

• The Elucidation of the Roadmap of Human Hematopoiesis and Isolation of Human HSC: Dr. Dick's research has provided invaluable insights into the composition and heterogeneity of the human HSC pool. His team developed a novel sorting approach, combined with single-cell functional assays, culminating in the first isolation of near-pure populations of ten different human HSC and progenitor fractions. Transcriptional profiling of these populations has yielded the first comprehensive analysis of the molecular regulation of early fate determination in human hematopoiesis. The isolation of a single HSC capable of regenerating the entire blood system represents a significant achievement that will advance our understanding of human HSC biology and enable substantial improvements in the clinical application of HSC-based therapies.

• The Unification of CSC and Genetic Diversity Models of Tumor Heterogeneity: Traditionally, the CSC and genetic evolution models describing tumour cell heterogeneity were viewed as mutually exclusive. Dr. Dick challenged this view and demonstrated that leukemia-initiating cells (L-IC) are genetically diverse and evolve through complex evolutionary lineage relationships. This work sets the stage for a unified view of cancer that accommodates both heterogeneity models, enhancing our understanding of tumour development and progression.

Current Research Projects and Goals

The long-term goal of our research program is to elucidate the mechanisms underpinning the stemness state of human hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs) and to transform these findings into new therapies and biomarkers. Simply put, guided by these fundamental research questions:

• What makes a stem cell a stem cell?
• Which stem cell properties are shared between HSCs and LSCs?
• Which are different?
• How do HSCs transform into LSCs?

Specifically, we are

1) Aiming to refine our new AML classification framework and advance it into clinical testing. By deploying the new hierarchy classification biomarkers on remission cells recovered from patients who are poised to eventually relapse, our research will unlock a new opportunity to consider clinical trials to prevent relapse through earlier targeting of relapse-fated LSC. (Funded by Ontario Institute for Cancer Research, Pre-Clinical Acceleration Translation Award; CIHR Foundation grant; CCSRI)

2) Advancing the mechanistic understanding of human leukemic processes and providing rich avenues of clinical translation, including the development of candidates for therapeutic targeting and novel biomarkers of relapse-fated subclones that permit monitoring of patients at risk for relapse. Our ultimate goal is targeting minor relapse-fated subclones while they remain vulnerable before they engender further mutational progression resulting in therapy-resistant relapse disease. (Funded by Terry Fox Research Institute, Program Project Grant; CIHR Foundation grant; CCSRI)

3) Focusing on age-related clonal hematopoiesis and cardiovascular disease by a) defining the specific genetic features that distinguish individuals with ARCH that are linked to increased risk of CVD with those of individuals with ARCH but who do not progress to CVD; b) investigating blood samples banked from individuals identified with ARCH-CVD risk and undertake single-cell transcriptional and epigenetic analysis of defined HSC, progenitors and mature lineage cells to determine the mechanism of how the specific features of ARCH-CVD perturb normal blood development to contribute to eventual CVD disease. (Funded by Medicine by Design, University of Toronto, Canada First Research Excellence Fund, Cycle 2 Award)

Courses

• Stem Cells I

Awards

• 1997 Michael Smith Award for Excellence - Medical Research Council of Canada
• 2000 Robert L. Noble Prize for Excellence in Cancer Research-National Cancer Institute of Canada
• 2002 5th Boerhaave Medal-Leiden University- Netherlands
• 2002 Canada Research Chair in Stem Cell Biology, University of Toronto
• 2004 Fellow of the Royal Society of Canada, Academy of Sciences
• 2005 William Dameshek Prize, American Society of Hematology
• 2007 Don Metcalf Award, International Society of Experimental Hematology
• 2007 Premier's Summit Award in Medical Research, Province of Ontario 2007 Diamond Jubilee Award (with JE Till, EA McCulloch), CCSRI
• 2008 48th Annual AACR-G.H.A. Clowes Memorial Award, The American Association for Cancer Research
• 2009 Men of Distinction Award, Israel Cancer Research Fund of Toronto
• 2009 Clifford Prize for Cancer Research, Centre for Cancer Biology, Uni. of Adelaide, Australia
• 2009 E. Donnall Thomas Prize, American Society of Hematology
• 2013 Outstanding Achievements in Cancer Research, Canadian Cancer Research Alliance
• 2014 Fellow of the Royal Society of London, United Kingdom
• 2016 Gold Leaf Prize for Discovery, Canadian Institutes for Health Research (CIHR)
• 2016 Fellow of the AACR Academy, (American Association for Cancer Research) USA
• 2017 International KFG Research Prize, Rigshospitalet, University of Copenhagen, Denmark
• 2017 Tobias Award, The International Society for Stem Cell Research (ISSCR), USA
• 2017 KEIO Medical Science Prize, Keio University, Japan
• 2018 Special Achievement Award, Miami Winter Symposium, Miami, USA
• 2018 Richard Hill Mentorship Award, Princess Margaret Cancer Centre, Toronto, Canada
• 2018 ASH Mentor Award, The American Society of Hematology, USA
• 2019 ISSCR Award for Innovation, International Society for Stem Cell Research (ISSCR), USA
• 2019 Dr. Chew Wei Memorial Prize in Cancer Research, University of British Columbia (UBC)
• 2020 Pezcoller Foundation-AACR International Award for Extraordinary Achievement in Cancer Research
• 2020 International Member of the US National Academy of Medicine (NAM)
• 2023 Inducted into the Canadian Medical Hall of Fame 

Cross-affiliations

• Princess Margaret Cancer Centre