Molecular Genetics of Cancer
Despite the usual negative connotation of “death”, programmed cell death (apoptosis) is a normal, essential and healthy process. It ensures the elimination of superfluous cells, while new cells develop in their place.
Our Division is identifying DNA alterations that provoke cancer, assessing how they affect therapy and exploring new approaches to diagnosis and treatment. We are concentrating on the roles of cell death and stem cells in cancer.
Regulated cell death (apoptosis) is essential for health. Our cells have a limited life span. Cells that are damaged or defunct are eliminated and replaced by new cells at the rate of one million per second. A cell that fails to die may continue to multiply and form a cancer. It is therefore important for us to determine how cell death is regulated. Opposing factions of the extended Bcl-2 protein family decide the cell’s fate. Its pro-survival members, such as Bcl-2, restrain their pro-death relatives Bak and Bax until BH3-only relatives issue the death warrant.
Recently, we discovered that the BH3-only protein Bmf instructs the demise of superfluous lymphocytes and that its absence promotes lymphomas. We also discovered a key step allowing Bak to kill cells: on escaping its pro-survival guards, Bak embraces another Bak protein, and this deadly duo then recruits more Bak to help break open the cell’s powerhouse, the mitochondrion. Our insights into apoptosis are revealing how best to kill cancer cells, using both conventional agents and a new class of agents that directly targets Bcl-2 family members.
We are also exploring how all the diverse differentiated cells within a tissue, such as the breast, derive from stem and progenitor cells. Pertinently, this process of differentiation is arrested in many tumours. Indeed, our work this year on mouse models of breast cancer suggests that certain breast tumours, but not others, may derive from stem cells. Such insights should pave the way to better diagnosis and treatment.
Professor Jerry Adams (Joint Division Head)
Professor Andreas Strasser (Joint Division Head)
Scientific Coordinator: Catherine McLean - contact Molecular Genetics of Cancer Division