Donald Metcalf

University of Melbourne

Election Year: 1987
Primary Section: 41, Medical Genetics, Hematology, and Oncology
Membership Type: Foreign Associate

Research Interests

As an experimental pathologist, I have studied the manner in which mature blood cells are formed by ancestral cells in the bone marrow. This required the development of clonal culture systems, allowing the progeny of individual cells to be analyzed. The formation and maturation of blood cells was found to be controlled by a family of glycoprotein regulators, and those controlling the formation of two interrelated white blood cells, the granulocytes and macrophages, now carry the name "Colony Stimulating Factors (CSFs)." The four CSFs were purified and can now be mass produced in recombinant form. The CSFs are now widely used clinically to stimulate blood cell formation, particularly in patients undergoing chemotherapy where the treatment damages bone marrow cells. We are currently generating mice with homozygous inactivation of genes encoding blood cell regulatory factors or their receptors to establish the precise functions attributable to each factor. Parallel studies are using mutagenized receptors to establish the domains in each receptor chain initiating each of the variety of signaling cascades required to mediate the pleiotropic actions each regulator has on responding cells.

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