The Walter and Eliza Hall Institute embarked on breast cancer research in 1997, when molecular biologist Professor Jane Visvader and clinician-scientist Professor Geoff Lindeman were recruited back from Harvard. Professor Visvader and Professor Lindeman now co-head the ACRF Stem Cells and Cancer division. Their team is deciphering the cellular and molecular controls on normal breast development and determining how these controls break down to cause breast cancer. In 2006 they identified the breast stem cell. They showed that a single rare cell isolated from a mouse mammary gland could generate a complete and fully functional breast gland. Their efforts are now focussed on discovering the human breast stem cell and clarifying its involvement in breast cancer. Insights from their work will aid the development of more effective therapies.
Leukaemia and lymphoma
Leukaemias and lymphomas are cancers of the blood cells, predominantly the infection-fighting white blood cells. Leukaemias present as excessive numbers of cells in the blood and bone marrow, whereas lymphomas present as nodular cellular masses in lymph nodes and other organs. Like other cancers, leukaemias and lymphomas result from an accumulation of several genetic errors. Some of these errors occur as an unfortunate side-effect of a natural DNA rearrangement process that takes place in all lymphocytes to enable them to recognise and destroy infected or damaged cells.
All blood cells develop from stem cells that reside in the marrow. In the mid-1960s, Professor Don Metcalf developed clonal assays for blood stem cells and their immature progeny. He and his colleagues subsequently isolated several of the hormones involved in stimulating these cells to produce the different types of white blood cells needed by the body to vanquish infections. Two of these hormones are now in clinical use for cancer patients, to replenish the vital blood cells destroyed by chemotherapy. Over 10 million patients world-wide have benefited.
During the first clinical trials of the cell signalling hormone G-CSF (granulocyte colony stimulating factor), carried out in The Royal Melbourne Hospital, Walter and Eliza Hall Institute researchers made the unexpected discovery that G-CSF mobilises stem cells from the bone marrow into the blood. G-CSF has revolutionised bone marrow transplantation and today, stem cells needed for transplantation are simply collected from the blood after a course of G-CSF rather than by a bone marrow harvest operation. Each year, tens of thousands of patients undergo blood stem cell transplantation as curative therapy for leukemias and lymphomas.
Using all the powerful tools afforded by the genomics revolution, diverse programs in seven divisions – ACRF Stem Cells and Cancer, ACRF Chemical Biology, Cancer and Haematology, Molecular Genetics of Cancer, Molecular Medicine, Structural Biology and Bioinformatics – are continuing the quest to understand in intimate detail how blood cell production is normally controlled and how it goes awry to produce the many different types of lymphoma and leukemia. They are also seeking to understand how these and other cancers resist standard therapy and are collaborating with leading biotechnology and pharmaceutical companies to develop more effective therapeutics. In the Cancer and Haematology division, Professor Andrew Roberts is leading translational research using samples from patients on clinical trials to rapidly generate knowledge about the effectiveness of these new therapeutics.
B cells turn into antibody-producing plasma cells to produce infection-fighting antibodies in the body. When a damaged B cell develops into a damaged plasma cell and keeps proliferating, a myeloma occurs. Using powerful new genetic technologies, researchers in the Immunology division are clarifying how and where plasma cells normally develop in the body. They are also searching for protein markers on the surface of normal and malignant plasma cells that could be used as targets for monoclonal antibody therapy against multiple myeloma. Scientists in the Molecular Genetics of Cancer division are developing mouse models of multiple myeloma that will be useful for testing new therapeutic strategies.