Research Location: Children's & Women's Health Centre of British Columbia

Huntington disease (HD) is a fatal degenerative brain disorder caused by a defective gene, which causes cells in specific parts of the brain to die. This leads to symptoms including progressive deterioration in the ability to control movements and emotions, recall recent events or make decisions, and leads to death 15 to 20 years after onset. One in 10,000 Canadians has HD, and children with a parent with HD have a 50 per cent risk of inheriting the disease. There is neither a cure nor treatments to prevent Huntington disease. The HD gene produces a protein called huntingtin, which breaks into short fragments that dramatically promote cell death. Little is known about the exact function and toxic properties of this mutant protein. Now Rona Graham is expanding her earlier Masters research into the mechanisms that cause shortened huntingtin. She is investigating other forms of mutant huntingtin to determine their role in creating HD, and hopes the results will lead to new therapies to prevent or alleviate this disease and other neurodegenerative disorders.

Building on his earlier research, which was supported by a MSFHR Trainee Award, Damon Poburko is now investigating the mechanisms involved in mitochondrial regulation of calcium. An average cell has several hundred mitochondria, which provide the energy for cells to function properly. Research has shown mitochondria are involved in programmed cell death, or apoptosis, when they take up large, toxic loads of calcium. In addition, mitochondria sense calcium changes, allowing them to tailor energy production to cell needs. Mitochondria also help regulate intracellular calcium levels, which determine blood vessel constriction in vascular muscle. The findings should help explain how vascular tone is regulated, and how blood is shunted to different parts of the body as needed. Ultimately, this research may lead to the development of new therapies to treat vascular diseases.

Huntington disease (HD) is an inherited, neurodegenerative disease characterized by loss of motor control and cognitive decline, eventually leading to death. Elizabeth Slow is studying atrophy and cell loss in the striatum, the most affected region of the brain, and the motor dysfunction associated with HD. A group of proteins called caspases split other proteins, including huntingtin, the protein produced by the HD gene. In collaboration with researchers at Harvard, the University of California and the Buck Institute in California, Elizabeth is investigating whether this process triggers inappropriate cell suicide in the neurons affected by HD, thus causing the disease. If so, the results will determine whether caspase inhibitors are an effective treatment option for people with Huntington disease, which currently has no treatments to prevent or delay the condition.

The frequency of chromosomal abnormalities in reproduction is significant — 15 to 20 per cent of all pregnancies end in spontaneous abortion, and half of these miscarriages are associated with chromosomal abnormalities. In 1983, two UBC professors discovered a condition now known as confined placental mosaicism (CPM), where a chromosomal abnormality is present in the placenta but not the fetus. CPM allows a pregnancy that would otherwise spontaneously abort to continue to term, and is present in at least two per cent of pregnancies. In his earlier research, Paul Yong confirmed that some types of CPM increase the risk for poor fetal outcomes such as low birth weight or complications such as pre-eclampsia. Now he is studying how chromosomal abnormalities cause alterations in placental structure and function. The hope is to identify potential therapeutic interventions in pregnancies affected by chromosome abnormalities in the placenta.

In developed countries, ovarian cancer is the leading cause of death from gynecologic malignancies in women. The five-year survival rate is only 35 to 40 per cent, a rate that hasn’t changed significantly in 25 years. The poor prognosis is due to the lack of a reliable test for early detection and the inability to identify early symptoms of the disease, which means the majority of ovarian tumours are diagnosed at an advanced stage. During progression to malignancy, normal ovarian surface epithelial cells, which give rise to the majority of epithelial ovarian cancers, acquire more complex and highly differentiated characteristics that most often resemble epithelial cells in the fallopian tube and uterus. This change may provide an advantage for growing cancer cells. Michelle Woo is screening ovarian tumour tissues for markers known to be present in the fallopian tube and uterus. She has recently discovered a protein in ovarian tumours that may be an early indicator of ovarian cancer. Another approach she is using to examine early changes in ovarian tumour progression involves the use of a unique three-dimensional culture system to mimic the development of ovarian tumours in women. Michelle hopes this research will identify new predictive markers that can be used for early screening and prevention of ovarian cancer.