Winter Issue — February 2007
Flicking Genetic Switches
Bone marrow transplants save the lives of thousands of Canadians suffering from leukemia and other blood diseases. Too often, however, the transplants fail – usually because the patient’s body rejects the foreign bone marrow cells.Dr. Marjorie Brand wants to end this practice with the goal of saving many more lives. Brand is developing a way to extract, alter and reinsert a patient’s own bone marrow cells. To do so, she delves deep into the mechanical operations of genes and proteins to understand the mechanisms that govern the formation of blood cells.
Genes hold our entire genetic code, but without proteins, they simply sit there, doing nothing. Gene expression is the process by which proteins perform their role, turning on and off desirable – or not so desirable – functions in genes. The study of proteins, called proteomics, is one of the most exciting areas of science today.
Brand’s target is hemoglobin, found in red blood cells. She is specifically trying to find the proteins – definitely dozens of them, probably hundreds – that stimulate the production of beta-globin. Beta-globin, in turn, stimulates the production of hemoglobin.
Brand holds the Canada Research Chair for the Regulation of Gene Expression at the University of Ottawa, and is a scientist at the Sprott Centre for Stem Cell Research at the Ottawa Health Research Institute, as well as an assistant professor in the Faculty of Medicine. She came to the University following a post-doctoral fellowship at the Fred Hutchinson Cancer Research Center in Seattle, Washington, where bone marrow transplants were first developed.
Identifying the proteins that will result in the expression of hemoglobin is the first step towards learning how to convince undifferentiated stem cells – cells found in bone marrow that have the potential to become many different kinds of cells –to become healthy blood cells. These cells could then be re-inserted into the body of a patient with a blood disease such as leukemia to replace the diseased blood cells. It is just like a bone marrow transplant, but without the risk of rejection.
Stopping the severe side effects of gene therapy, which can prevent it from becoming an effective weapon of disease treatment, is the other goal of Brand’s research. She cites one trial, in France, where infants with non-functioning immune systems –“bubble babies” – received gene therapy. The therapy repaired their immune systems, but there were consequences: some of the patients developed leukemia because other non-desirable genes were “turned on” as a side effect.
“Our goal is to prevent these kinds of things from happening by understanding how to control gene expression,” she says.
Brand’s work attacks cancer with leading-edge technology. The ICAT (Isotope Coded Affinity Tag) mass spectrometry technique allows her to see changes quantitatively between two cells, such as those between a stem cell and a blood cell.
An equipment grant from the Canada Foundation for Innovation, which accompanied her Canada Research Chair, together with funding from other sources, supported the purchase of the mass spectrometer. In November 2006, Brand moved into the new Sprott Stem Cell Research Centre, where the mass spectrometer now resides in her lab.
Brand also receives funding from the Terry Fox Foundation (National Cancer Institute of Canada), Human Frontier Science Program and the Canadian Institutes of Health Research.
Brand knows that it could be many years, even decades, before her work leads to concrete benefits for people with diseases. However, she says, that is the nature of basic research.
“You can’t only do research with short-term, directly applicable goals. Often what you find isn’t what you thought you were looking for.”
