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Ernest Armstrong McCulloch | |
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| Born | 27 April 1926 |
| Died | 19 January 2011 (aged 84) |
| Education | |
| Known for | stem cells |
| Awards | |
| Scientific career | |
| Fields | Cell biology |
| Institutions | |
| Doctoral students | Anne Croy |
Ernest Armstrong McCulloch OC OOnt FRS FRSC [1] (27 April 1926 [2] – 20 January 2011) [3] was a University of Toronto cellular biologist, best known for demonstrating – in a partnership with James Till – the existence of stem cells. [2]
McCulloch was born in Toronto, Ontario, Canada on 27 April 1926, [2] [4] and was educated at Upper Canada College and the University of Toronto. [5]
Ernest McCulloch received his MD in 1948 from the University of Toronto. Upon graduation, he began his education in research at the Lister Institute in London, England.
In 1957 he joined the newly formed Ontario Cancer Institute, where the majority of his research focused on normal blood-formation and leukaemia. Together with his colleague, Dr. J.E. Till, McCulloch created the first quantitative, clonal method to identify stem cells and used this technique for pioneering studies on stem cells. His experience in hematology, when combined with Till's experience in biophysics, yielded a novel and productive combination of skills and interests.
In the early 1960s, McCulloch, and Till started a series of experiments that involved injecting bone marrow cells into irradiated mice. Visible nodules were observed in the spleens of the mice, in proportion to the number of bone marrow cells injected. Till and McCulloch called the nodules 'spleen colonies', and speculated that each nodule arose from a single marrow cell: perhaps a stem cell.
In later work, Till & McCulloch were joined by graduate student Andy Becker, and demonstrated that each nodule did indeed arise from a single cell. They published their results in Nature in 1963. In the same year, in collaboration with Lou Siminovitch, a trailblazing Canadian molecular biologist, they obtained evidence that these cells were capable of self-renewal, a crucial aspect of the functional definition of stem cells that they had formulated.[ citation needed ]
McCulloch's later research was on cellular and molecular mechanisms affecting the growth of malignant blast stem cells obtained from the blood of patients with Acute Myeloblastic Leukemia.
In 1969, McCulloch won the Canada Gairdner International Award with James E. Till in recognition of their development of the spleen colony technique for measuring the capacity of primitive normal and neoplastic cells to multiply and differentiate in the body. [6] This technique has been applied by them and their colleagues, and by many others, to gain important knowledge of the normal formation of blood cells, the behavior of leukemic cells and methods of treating leukemia, and other aspects of cell biology. [6]
In 1974, McCulloch became a Fellow of the Royal Society of Canada. In 1988, he became an Officer of the Order of Canada and was made a member of the Order of Ontario in 2006. In 1999, he was elected a Fellow of the Royal Society. [1] In 2004, McCulloch was inducted into the Canadian Medical Hall of Fame. He holds the distinguished title of University Professor Emeritus at the University of Toronto.
In 2005, he and James Till were awarded the Albert Lasker Award for Basic Medical Research.
Haematopoiesis is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten billion to a hundred billion new blood cells are produced per day, in order to maintain steady state levels in the peripheral circulation.
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.
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.
Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along with mast cells and basophils, they also control mechanisms associated with allergy and asthma. They are granulocytes that develop during hematopoiesis in the bone marrow before migrating into blood, after which they are terminally differentiated and do not multiply.
Erythropoiesis is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell.
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.
Louis Siminovitch was a Canadian molecular biologist. He was a pioneer in human genetics, researcher into the genetic basis of muscular dystrophy and cystic fibrosis, and helped establish Ontario programs exploring genetic roots of cancer.
Primary myelofibrosis (PMF) is a rare bone marrow blood cancer. It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is activation and growth of mutated cells in the bone marrow. This is most often associated with a somatic mutation in the JAK2, CALR, or MPL genes. In PMF, the bony aspects of bone marrow are remodeled in a process called osteosclerosis; in addition, fibroblast secrete collagen and reticulin proteins that are collectively referred to as (fibrosis). These two pathological processes compromise the normal function of bone marrow resulting in decreased production of blood cells such as erythrocytes, granulocytes and megakaryocytes, the latter cells responsible for the production of platelets.
James Edgar Till is a University of Toronto biophysicist, best known for demonstrating – in a partnership with Ernest McCulloch – the existence of stem cells.
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.
A megakaryoblast is a precursor cell to a promegakaryocyte. During thrombopoiesis, the promegakaryocyte matures into the form of a megakaryocyte. From the megakaryocyte, platelets are formed. The megakaryoblast is the beginning of the thrombocytic series or platelet forming series.
Constance Jean Eaves CorrFRSE was a Canadian biologist with significant contributions to cancer and stem cell research. Eaves was a professor generics of genetics at the University of British Columbia and was also the co-founder with Allen C Eaves of Terry Fox Laboratory.
Plerixafor, sold under the brand name Mozobil, is an immunostimulant used to mobilize hematopoietic stem cells in cancer patients into the bloodstream. The stem cells are then extracted from the blood and transplanted back to the patient. The drug was developed by AnorMED, which was subsequently bought by Genzyme.
Janet Rossant, is a developmental biologist well known for her contributions to the understanding of the role of genes in embryo development. She is a leader in developmental biology. Her current research interests focus on stem cells, molecular genetics, and developmental biology. Specifically, she uses cellular and genetic manipulation techniques to study how genes control both normal and abnormal development of early mouse embryos. Rossant has discovered information on embryo development, how multiple types of stem cells are established, and the mechanisms by which genes control development. In 1998, her work helped lead to the discovery of the trophoblast stem cell, which has assisted in showing how congenital anomalies in the heart, blood vessels, and placenta can occur.
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.
Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells or medicinal signaling cells, are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts, chondrocytes, myocytes and adipocytes.
Working together, biologists James Till and Ernest McCulloch made significant contributions to stem cell research. While studying the effects of radiation on the bone marrow of mice at the Ontario Cancer Institute in Toronto, they demonstrated the existence of multipotent stem cells in 1961, helping lay the foundation for modern stem cell biology and regenerative medicine.
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.
Gillian Elizabeth Wu is a Canadian Immunologist and the former Dean of Pure and Applied Science at York University. She is currently Professor Emerita in York University's Faculty of Science and Faculty of Health and also at the University of Toronto Faculty of Medicine.
Alan Ming-ta Wu was a Taiwanese-American molecular biologist and immunologist who developed techniques to grow hematopoietic stem cells in cell culture.
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