John Edgar Dick

Last updated
John Dick
FRS FRSC
Professor John Dick FRS.jpg
John Dick at the Royal Society admissions day in London in 2014
Born
John Edgar Dick

1954 (age 69–70)
Alma mater University of Manitoba (PhD)
Awards Robert L. Noble Prize (2000)
Scientific career
Fields
Institutions
Thesis [ ProQuest   303339990 Studies on Ribonucleotide Reductase from Normal Senescing Human Diploid Fibroblasts] (1984)
Website jdstemcellresearch.ca

John Edgar Dick FRS FRSC [2] (born 1954) is Canada Research Chair in Stem Cell Biology, Senior Scientist at the Princess Margaret Cancer Centre, University Health Network and Professor in the Department of Molecular Genetics at the University of Toronto in Canada. [3] Dick is credited with first identifying cancer stem cells in certain types of human leukemia. [4] His revolutionary findings highlighted the importance of understanding that not all cancer cells are the same and thus spawned a new direction in cancer research. [1] [5] [6] [7] Dick is also known for his demonstration of a blood stem cell's ability to replenish the blood system of a mouse, his development of a technique to enable an immune-deficient mouse to carry and produce human blood, and his creation of the world's first mouse with human leukemia. [5] [8] [9] [10] [3] [11] [12]

Contents

Early life and education

Dick was raised on a farm in southern Manitoba. His early education was gained in a one-room schoolhouse. Later he moved to Winnipeg to study to become an X-ray technician. There he noticed one of his roommates was attending university and studying biology. Dick realized he was more interested in biology and decided to switch pursuits. [5]

Dick started off at the University of Manitoba specializing in microbiology [5] [13] and graduating with a Doctor of Philosophy degree in 1984. [14]

Career and research

In 1984, he moved to Toronto. In order to support his wife and two children, Dick worked part-time at an X-ray lab while he finished his post-doctorate work in Alan Bernstein’s lab. Bernstein, a noted cancer researcher whose Ph.D. advisor was James Till at the Ontario Cancer Institute, guided Dick to research cancers of the blood. [5]

Over the next five years, Dick developed an in vivo repopulation assay using the NOD/SCID mouse. This technique of using an immune-deficient mouse to generate human hematopoietic cells won Dick international recognition. [5] [15] [16]

In 1994, Nature [17] published his paper which described how cancer stem cells grow slowly. Dick explained, "Most kinds of chemotherapy are designed to kill fast-growing cancer cells. This is why leukemia can come back after treatment. To get rid of the cancer, you have to find ways of eliminating the stem cells." Many researchers dismissed Dick's discovery as interesting, but something not likely to apply to solid tumours. [5]

In 1997, Dick reported the detection of cancer stem cells at the root of three other forms of leukemia. This time he presented it as the "cancer stem-cell hypothesis". His model stated that there are different cancer cells and amongst them there is a pecking order in which the abnormal stem cell, is both the key to forming and feeding a cancer. Therefore, without an abnormal stem cell, cancers will not grow. This time his report was considered a breakthrough. [5] [18]

Dick has transformed the study of human hematopoiesis and leukemogenesis, with his development of methodologies for transplanting human bone marrow into immune-deficient mice, with resultant multilineage repopulation of murine bone marrow and other hematopoietic tissues. [2] Using this approach, he has identified long-term repopulating human hematopoietic stem cells and generated mouse models of leukaemia. [2] His studies showing that a specific subset of leukemic cells are actually capable of recapitulating tumour growth are recognised as the foundation for all current work on the cancer stem cell model and its application to cancer therapy. [2]

As of 2006, Dick is a Senior Scientist in the Division of Cellular & Molecular Biology of the Toronto General Research Institute, and founding member of Canada's Stem Cell Network. [15] [19]

Awards and honours

Dick's awards and honours include:

Related Research Articles

<span class="mw-page-title-main">Stem cell</span> Undifferentiated biological cells that can differentiate into specialized cells

In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell in a cell lineage. They are found in both embryonic and adult organisms, but they have slightly different properties in each. They are usually distinguished from progenitor cells, which cannot divide indefinitely, and precursor or blast cells, which are usually committed to differentiating into one cell type.

<span class="mw-page-title-main">Bone marrow</span> Semi-solid tissue in the spongy portions of bones

Bone marrow is a semi-solid tissue found within the spongy portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production. It is composed of hematopoietic cells, marrow adipose tissue, and supportive stromal cells. In adult humans, bone marrow is primarily located in the ribs, vertebrae, sternum, and bones of the pelvis. Bone marrow comprises approximately 5% of total body mass in healthy adult humans, such that a man weighing 73 kg (161 lbs) will have around 3.7 kg (8 lbs) of bone marrow.

<span class="mw-page-title-main">Hematopoietic stem cell</span> Stem cells that give rise to other blood cells

Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the (midgestational) aorta-gonad-mesonephros region, through a process known as endothelial-to-hematopoietic transition. In adults, haematopoiesis occurs in the red bone marrow, in the core of most bones. The red bone marrow is derived from the layer of the embryo called the mesoderm.

<span class="mw-page-title-main">CD34</span> Cluster of differentiation protocol that identifies cell surface antigens.

CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species.

<span class="mw-page-title-main">Ernest McCulloch</span> Canadian cellular biologist (1926–2011)

Ernest Armstrong McCulloch was a University of Toronto cellular biologist, best known for demonstrating – with James Till – the existence of stem cells.

<span class="mw-page-title-main">Cancer stem cell</span> Cancer cells with features of normal cells

Cancer stem cells (CSCs) are cancer cells that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. CSCs are therefore tumorigenic (tumor-forming), perhaps in contrast to other non-tumorigenic cancer cells. CSCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple cell types. Such cells are hypothesized to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. Therefore, development of specific therapies targeted at CSCs holds hope for improvement of survival and quality of life of cancer patients, especially for patients with metastatic disease.

Tak Wah Mak, is a Canadian medical researcher, geneticist, oncologist, and biochemist. He first became widely known for his discovery of the T-cell receptor in 1983 and pioneering work in the genetics of immunology. In 1995, Mak published a landmark paper on the discovery of the function of the immune checkpoint protein CTLA-4, thus opening the path for immunotherapy/checkpoint inhibitors as a means of cancer treatment. Mak is also the founder of Agios Pharmaceuticals, whose lead compound, IDHIFA®, was approved by the FDA for acute myeloid leukemia in August 2017, becoming the first drug specifically targeting cancer metabolism to be used for cancer treatment. He has worked in a variety of areas including biochemistry, immunology, and cancer genetics.

<span class="mw-page-title-main">Adult stem cell</span> Multipotent stem cell in the adult body

Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues. Also known as somatic stem cells, they can be found in juvenile, adult animals, and humans, unlike embryonic stem cells.

<span class="mw-page-title-main">X-linked severe combined immunodeficiency</span> Medical condition

X-linked severe combined immunodeficiency (X-SCID) is an immunodeficiency disorder in which the body produces very few T cells and NK cells.

<span class="mw-page-title-main">Wilms tumor protein</span> Transcription factor gene involved in the urogenital system

Wilms tumor protein (WT33) is a protein that in humans is encoded by the WT1 gene on chromosome 11p.

<span class="mw-page-title-main">HOXA9</span> Protein-coding gene in humans

Homeobox protein Hox-A9 is a protein that in humans is encoded by the HOXA9 gene.

<span class="mw-page-title-main">Sean J. Morrison</span>

Sean J. Morrison is a Canadian-American stem cell biologist and cancer researcher. Morrison is the director of Children's Medical Center Research Institute at UT Southwestern (CRI), a nonprofit research institute established in 2011 as a joint venture between Children’s Health System of Texas and UT Southwestern Medical Center. With Morrison as founding director, CRI was established to perform transformative biomedical research at the interface of stem cell biology, cancer and metabolism to better understand the biological basis of disease. He is a Howard Hughes Medical Institute Investigator, has served as president of the International Society for Stem Cell Research, and is a member of the U.S. National Academy of Medicine, U.S. National Academy of Sciences and European Molecular Biology Organization.

A humanized mouse is a genetically modified mouse that has functioning human genes, cells, tissues and/or organs. Humanized mice are commonly used as small animal models in biological and medical research for human therapeutics.

The NSG mouse is a brand of immunodeficient laboratory mice, developed and marketed by Jackson Laboratory, which carries the strain NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ. NSG branded mice are among the most immunodeficient described to date. NSG branded mice lack mature T cells, B cells, and natural killer (NK) cells. NSG branded mice are also deficient in multiple cytokine signaling pathways, and they have many defects in innate immunity. The compound immunodeficiencies in NSG branded mice permit the engraftment of a wide range of primary human cells, and enable sophisticated modeling of many areas of human biology and disease. NSG branded mice were developed in the laboratory of Dr. Leonard Shultz at Jackson Laboratory, which owns the NSG trade mark.

Allen Charles Edward Eaves is the co-founding Director of the Terry Fox Laboratory for Hematology/Oncology Research, which over a 25-year period (1981–2006) he grew into an internationally recognized centre for the study of leukemia and stem cell research. His own research on chronic myelogenous leukemia (CML) has led the way to a new understanding of the disease. As Head of Hematology at the British Columbia Cancer Agency and the University of British Columbia for 18 years (1985–2003) he engineered the building of one of the first and largest bone marrow transplant programs in Canada. In recognition of his research accomplishments and leadership in moving basic science discoveries in stem cell biology into the clinic, he was elected President of the International Society of Cellular Therapy (1995–1997), Treasurer of the Foundation for the Accreditation of Cellular Therapy (1995–2002) and President of the American Society of Blood and Marrow Transplantation (1999–2000). In 2003 he was awarded the prestigious R. M. Taylor Medal by the Canadian Cancer Society and the National Cancer Institute of Canada.

Many human blood cells, such as red blood cells (RBCs), immune cells, and even platelets all originate from the same progenitor cell, the hematopoietic stem cell (HSC). As these cells are short-lived, there needs to be a steady turnover of new blood cells and the maintenance of an HSC pool. This is broadly termed hematopoiesis. This event requires a special environment, termed the hematopoietic stem cell niche, which provides the protection and signals necessary to carry out the differentiation of cells from HSC progenitors. This stem-cell niche relocates from the yolk sac to eventually rest in the bone marrow of mammals. Many pathological states can arise from disturbances in this niche environment, highlighting its importance in maintaining hematopoiesis.

Patient derived xenografts (PDX) are models of cancer where the tissue or cells from a patient's tumor are implanted into an immunodeficient or humanized mouse. It is a form of xenotransplantation. PDX models are used to create an environment that allows for the continued growth of cancer after its removal from a patient. In this way, tumor growth can be monitored in the laboratory, including in response to potential therapeutic options. Cohorts of PDX models can be used to determine the therapeutic efficiency of a therapy against particular types of cancer, or a PDX model from a specific patient can be tested against a range of therapies in a 'personalized oncology' approach.

Mice with severe combined immunodeficiency (SCIDs) are often used in the research of human disease. Human immune cells are used to develop human lymphoid organs within these immunodeficient mice, and many different types of SCID mouse models have been developed. These mice allow researchers to study the human immune system and human disease in a small animal model.

<span class="mw-page-title-main">Shimon Slavin</span> Israeli professor of medicine

Shimon Slavin is an Israeli professor of medicine. He pioneered immunotherapy mediated by allogeneic donor lymphocytes and innovative methods for stem cell transplantation to cure hematological malignancies and solid tumors. He also used hematopoietic stem cells to induce transplantation tolerance to bone marrow and organ allografts.

Since haematopoietic stem cells cannot be isolated as a pure population, it is not possible to identify them under a microscope. Therefore, there are many techniques to isolate haematopoietic stem cells (HSCs). HSCs can be identified or isolated by the use of flow cytometry where the combination of several different cell surface markers is used to separate the rare HSCs from the surrounding blood cells. HSCs lack expression of mature blood cell markers and are thus, called Lin-. Lack of expression of lineage markers is used in combination with detection of several positive cell-surface markers to isolate HSCs. In addition, HSCs are characterized by their small size and low staining with vital dyes such as rhodamine 123 or Hoechst 33342.

References

  1. 1 2 Baker, M. (2009). "John Dick: Careful assays for cancer stem cells". Nature Reports Stem Cells: 1. doi: 10.1038/stemcells.2009.47 .
  2. 1 2 3 4 5 Anon (2014). "Dr John Dick FRS". royalsociety.org. London: Royal Society. One or more of the preceding sentences incorporates text from the royalsociety.org website where:
    "All text published under the heading 'Biography' on Fellow profile pages is available under Creative Commons Attribution 4.0 International License." -- "Terms, conditions and policies | Royal Society". Archived from the original on 2016-11-11. Retrieved 2018-09-12.{{cite web}}: CS1 maint: bot: original URL status unknown (link)
  3. 1 2 John Edgar Dick publications indexed by the Scopus bibliographic database. (subscription required)
  4. ↑ Dick, J (2013). "Q&A: John Dick on Stem Cells and Cancer". Cancer Discovery. 3 (2): 131. doi: 10.1158/2159-8290.CD-ND2013-002 . PMID   23400460.
  5. 1 2 3 4 5 6 7 8 Meet the A-Team of stem-cell science . Retrieved from The Globe and Mail on November 27, 2006. Archived February 20, 2007, at the Wayback Machine
  6. ↑ Canadian Cancer Society- John Dick Bio Archived May 3, 2007, at the Wayback Machine
  7. ↑ University Health Network- John E Dick Bio
  8. ↑ Canadian researchers 'create' leukemia stem cell, watch disease unfold . CBC News, April 26, 2007.[ dead link ]
  9. ↑ Bonnet, D.; Dick, J. E. (1997). "Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell". Nature Medicine. 3 (7): 730–7. doi:10.1038/nm0797-730. PMID   9212098. S2CID   205381050.
  10. ↑ o’Brien, C. A.; Pollett, A.; Gallinger, S.; Dick, J. E. (2006). "A human colon cancer cell capable of initiating tumour growth in immunodeficient mice". Nature. 445 (7123): 106–10. doi:10.1038/nature05372. PMID   17122772. S2CID   4419499.
  11. ↑ Larochelle, A.; Vormoor, J.; Hanenberg, H.; Wang, J. C. Y.; Bhatia, M.; Lapidot, T.; Moritz, T.; Murdoch, B.; Xiao, X. L.; Kato, I.; Williams, D. A.; Dick, J. E. (1996). "Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: Implications for gene therapy". Nature Medicine. 2 (12): 1329–37. doi:10.1038/nm1296-1329. PMID   8946831. S2CID   2975811.
  12. ↑ Clarke, M. F.; Dick, J. E.; Dirks, P. B.; Eaves, C. J.; Jamieson, C. H. M.; Jones, D. L.; Visvader, J.; Weissman, I. L.; Wahl, G. M. (2006). "Cancer Stem Cells--Perspectives on Current Status and Future Directions: AACR Workshop on Cancer Stem Cells". Cancer Research. 66 (19): 9339–44. doi:10.1158/0008-5472.CAN-06-3126. PMID   16990346.
  13. ↑ Dick, J. E.; Wright, J. A. (1985). "On the importance of deoxyribonucleotide pools in the senescence of cultured human diploid fibroblasts". FEBS Letters. 179 (1): 21–4. Bibcode:1985FEBSL.179...21D. doi: 10.1016/0014-5793(85)80182-4 . PMID   3965302.
  14. ↑ Dick, John Edgar (1984). Studies on Ribonucleotide Reductase from Normal Senescing Human Diploid Fibroblasts (PhD thesis). University of Manitoba. OCLC   1033141481. ProQuest   303339990.[ page needed ][ non-primary source needed ]
  15. 1 2 "Black Box" of Cancer Breaks Open Archived 2007-09-28 at the Wayback Machine . Retrieved from American Society of Hematology website on November 27, 2006.
  16. 1 2 3 New Research Breakthroughs at UHN January 2003 Archived 2007-05-27 at the Wayback Machine . Retrieved from University Hospital Network website on November 27, 2006.
  17. ↑ Lapidot, T; Sirard, C; Vormoor, J; Murdoch, B; Hoang, T; Caceres-Cortes, J; Minden, M; Paterson, B; Caligiuri, M. A.; Dick, J. E. (1994). "A cell initiating human acute myeloid leukaemia after transplantation into SCID mice". Nature. 367 (6464): 645–8. Bibcode:1994Natur.367..645L. doi:10.1038/367645a0. PMID   7509044. S2CID   4330788.
  18. ↑ Stem Cells May Be Key to Cancer . Retrieved from The New York Times on November 27, 2006.
  19. ↑ Governor Schwarzenegger Highlights California-Canada Partnership on Life-saving Stem Cell Research . Press Release, May 30, 2007 Archived June 13, 2007, at the Wayback Machine
  20. ↑ Ontario Ministry of Research and Innovation - Premier's Summit Award Archived 2007-08-29 at the Wayback Machine
  21. ↑ "The 2017 Keio Medical Science Prize Laureate". Archived from the original on 12 December 2017. Retrieved 12 December 2017.
  22. ↑ "THE PEZCOLLER FOUNDATION-AACR INTERNATIONAL AWARD FOR EXTRAORDINARY ACHIEVEMENT IN CANCER RESEARCH".

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