Research Location: BC Cancer Agency - Vancouver

Stem cells have the unique ability to develop into different types of tissue cells in the human body, and are often involved in the onset of cancer, especially leukemia. Like other cells in the body, stem cells activate a diverse family of proteins that pump different substances in and out of cells, called ABC transporters. In normal cells, these proteins pump toxic substances out and useful ones in. But some of these proteins also pump anti-cancer drugs out of cancer cells, causing the treatment to fail. Maria Ho is researching how ABC transporters in stem cells can cause drug resistance in leukemia. Maria is measuring the level of ABC transporters in chemo-refractory and responsive leukemic stem cells to determine which transporters are required for normal functions and which ones are related to cancer. This research will help explain the course of the disease and lead to more effective cancer treatments to target the transporters involved in leukemia.

Programmed cell death occurs when cells respond to internal or external signals by initiating a process that results in their own death. While this process is necessary for the normal development of organisms, errors in the process can cause diseases such as cancer or neurodegenerative illnesses. Erin Pleasance is working to identify new genes that are expressed (activated) in programmed cell death and determine their role in diseases such as cancer. Using specialized equipment at the BC Cancer Agency’s Genome Sciences Centre, she is studying the fruit fly to find genes whose role in cell death has not yet been defined. The fruit fly is a useful model because the proteins and mechanisms involved in its cell death correspond to those in mammals and can be used to help identify cancer-causing genes in humans. Learning how to inhibit genes that prevent cell death may lead to the development of new anti-cancer drugs that stop cell growth.

Josette-Renée Landry is bringing both computer science and traditional molecular biology techniques to her research into the function of repetitive DNA sequences in the human genome (full collection of human genes). The Human Genome Project, completed in February 2001, revealed that more than 40 per cent of the human genome consists of repetitive sequences whose function remains largely unknown. Studies have suggested that some of these repeats, called retroelements, can influence how genes are expressed (turned on and off). Josette-Renée is working to further understanding of the function of retroelements by searching for repeats that appear to be involved in regulation of human genes. She will then use laboratory techniques to determine how these elements are involved in gene expression. Her work could lead to the discovery of important new gene regulatory factors. Since many genetic disorders result from aberrant gene regulation, the identification of retroelements that play a role in normal gene expression may provide insight into how regulatory mechanisms are altered in diseases such as cancer.

Current treatments for advanced prostate cancer eliminate the growth-promoting effects of androgens such as testosterone. Unfortunately, while this treatment is initially effective in reducing prostate growth, the usual outcome is an untreatable form of prostate cancer where the cancer becomes androgen-independent (grows without androgens). Steven Quayle is working to isolate the different genes that are expressed (activated) at different hormonal stages of prostate cancer. He is using a technique where prostate cancer cells grown in hollow fibres progress to androgen-independence in a controlled, reproducible manner. This will allow Steven to confirm the changes in gene expression that consistently occur with disease progression, and study in more detail the role of particular genes. These genes may be useful as indicators of disease progression, as well as potential targets for treatment.

Over the last ten years, researchers have identified all the genes in our species—approximately 40,000 genes—called the human genome. The mouse genome will be completed soon. It’s estimated that mice and humans shared a common ancestor 70-100 million years ago, and we still share many of the same genes. Dr. Mia Klannemark is using specialized computer programs to compare data on mouse and human genes. She hopes to gain insight into regulatory regions adjacent to genes, which control the production of proteins. Mia is examining how genes make proteins, and identifying which regulatory regions have remained the same between mice and humans, because these genes indicate important functions that have not changed over the period of evolution. She is also identifying genes that have changed, which may contribute to the differences between species. This knowledge will help us understand how genetic variation influences the development of disease, and could lead to more effective treatments.

New blood vessels can grow from existing blood vessels in a process called angiogenesis. Limiting new blood vessel growth is a promising approach to treating cancer because tumours require a blood vessel supply to grow larger than two to three millimetres or to metastasize (spread) to other sites. But much remains to be learned about the molecular mechanisms of angiogenesis in tumours. In earlier research, Dr. Michela Noseda and colleagues have shown that a protein called Notch4 can inhibit angiogenesis. Notch arrests growth in the endothelial cells that line the inside of blood vessels, but it’s not known how this process occurs. In her current research project, Michela will investigate how the Notch protein prevents endothelial cells from proliferating. Ultimately, she wants to discover whether manipulating Notch activity in tumour blood vessels can induce tumour regression and limit metastasis.

While early detection is key to the successful treatment of many types of cancer, tumours still often go undetected and untreated until they are well advanced. Using information generated by the cancer genomics project at the BC Cancer Agency’s Genome Sciences Centre, Dr. Greg Vatcher’s research focuses on gene expression analysis-identifying genes that are activated in the earliest stages of cancer. He is hoping gene expression analysis can help detect tumours earlier. He is also conducting work to determine if tests can predict whether a person will develop cancer, based on pre-cancer genetic changes. Greg is bringing together information from multiple genomics projects, including data from the recently-completed Human Genome Project. For example, he’s taking genetic data being gathered on the normal aging process and relating it to his cancer study to determine if there are any common genetic components.