Regulation of energy balance in Stearoyl-CoA Desaturase-1 deficiency

Until recently, it was believed that the body burned fat only in response to hormones in the blood. However, new evidence shows that neurotransmitters in the brain play an active role in controlling energy use. Dr. William Gibson is studying how the brain uses the liver to control fat burning. He is investigating how the brain reduces activity of the SCD-1 enzyme (steroyl-CoA desaturase-1) to increase fat burning. Findings from this research may help to explain the molecular basis of human obesity, and lead to safe methods for reducing fat storage in people who are overweight and obese. Dr. Gibson also has a clinical interest in rare, monogenic obesity syndromes.

The early external cephalic version 2 trial

Of almost 40,000 babies born in BC in 2002, nearly 2,000 (4.8 percent) were breech (their bottom and legs were born before their heads). Research shows that breech babies are most safely delivered by Caesarean section. However, Caesareans cause more complications than vaginal births, and the resulting scar on the uterus complicates subsequent pregnancies. When a baby is found to be in a breech position using ultrasound, care providers can try to turn a baby to a head down position by feeling the baby through the mother’s abdomen and moving the baby’s head downward and its bottom upward. This procedure is called external cephalic version (ECV), and studies have shown that the chance of both breech birth and Caesarean section is reduced if ECV is performed close to the end of pregnancy (after 37 weeks). Dr. Eileen Hutton and her team of researchers from across Canada are conducting The Early ECV 2 Trial, which is an international randomised controlled trial designed to investigate whether performing ECV earlier in pregnancy, at 34-35 weeks, further decreases the number of Caesarean sections without increasing the risk of preterm birth. Dr. Hutton, founder and editor of the Canadian Midwifery Journal of Research and Practice, is also involved in a large international trial investigating the best way for twins to be born (vaginally or by Caesarean section), and is doing work in BC investigating patient initiated Caesarean section.

Role of Huntingtin phosphorylation by Akt in HD

Huntington’s disease (HD) is a fatal neurodegenerative disorder that usually begins in mid-life and causes progressive loss of motor control and mental capacity. One in 10,000 Canadians has this untreatable and devastating inherited disease. The HD gene produces the huntingtin protein, a protective molecule found in all regions of the human brain. However, when the HD gene mutates, it causes specific nerve cells to degenerate. Simon Warby aims to identify the factors that enable this location-specific and age-dependent degeneration in the brain. An important enzyme called Akt regulates the protective functions of huntingtin. Simon is investigating whether alterations in this enzyme and reduced levels of a molecule called BDNF (brain derived neurotrophic factor) turn off huntingtin’s protective functions. The research could contribute to therapies for reversing the degenerative process that characterize Huntington disease.

Intestinal innate immunity: recognition and response to enteric bacterial pathogens

Bacterial infections of the gastrointestinal tract are very common, particularly among children. These infections cause diarrheal outbreaks and millions of deaths worldwide. Bacteria are also a major problem in Canada, with BC having one of the highest rates of intestinal bacterial infection in the country. Bacteria are believed to trigger a variety of gastrointestinal diseases, including inflammatory bowel disease, a debilitating and chronic condition that affects one in every 1,000 Canadians. Despite the prevalence of bacterial pathogens (disease-causing organisms), little is known about how the immune system recognizes and combats intestinal bacterial infections. This information is important because the immune response to these bacteria determines who is susceptible to infection, as well as the severity of the resulting disease. Dr. Bruce Vallance is researching how bacteria cause intestinal disease and how the immune system identifies and fights these infections. Dr. Vallance is investigating whether genetic differences in hosts influence susceptibility to food and water-borne bacteria. He aims to identify immune responses and genetic factors that either protects against intestinal bacteria or causes susceptibility to infection. This research could help explain how bacteria cause intestinal disease and ultimately lead to new treatments to prevent both bacterial infections and bacterial-induced gastrointestinal diseases.

Addressing needs through action: what can be done to help HIV positive kids (8 and up) to ""live positively"" in BC within their broader healthcare community?

There is little published information about Canadian children with HIV especially about the health-related needs of adolescents. Yet it is during this period when they begin dealing with issues such as disclosure, psychosocial therapy, HIV prevention and sexual health, that support is most needed. Sarah Fielden is examining the health needs of children with HIV and developing strategies to meet them. Her research involves conducting focus groups with children and adolescents, families and service providers to capture a range of perspectives on this issue, and to specifically explore factors in the health system and community that allow children and adolescents to “live positively”. Sarah’s aim is to help improve the health and health care of children with HIV, and assist health care providers, academics, organizations and families in developing effective, age-appropriate interventions.

Focused attention, exploration and heart rate at 8-months in relation to prematurity and maternal interaction

Premature infants spend critical periods of early development in neonatal intensive care. The stress and pain experienced as part of early medical care can lead to the disorganization of infant behaviour or physiologic states, which may reflect risk for adverse neurodevelopment. Research links early stress to changes in brain stress circuits and heart rate regulation and follow-up studies show that high-risk premature infants have a high incidence of attention related deficits. Julianne Petrie-Thomas is examining the complex relationships between behavioural and physiological regulation of attention by studying focused attention and patterns of heart rate in premature infants at 8-months compared with term-born controls. As the infant’s interactions with its mother play an essential role in the regulation of behavioural as well as internal physiological systems, she is also studying the effects of maternal-infant interaction on infants’ behaviour and physiology. The findings could fill major gaps in understanding of how attention problems develop in premature infants and lead to interventions that significantly improve the developmental outcomes of these vulnerable babies.

Truncation of huntingtin and its relationship to the pathogenesis of Huntington's Disease

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.

Impact of delayed childbearing in BC, Canada

Women in developed societies around the world increasingly delay childbearing until the age of 35 or older. In BC, women who are 35 or older account for about 8,000 births a year. There has been little research into the effects of delayed childbearing, and studies that have been undertaken produced contrasting results. Some research suggested an increased risk of complications and other studies showed no greater risk. No research has compared differences in rural and urban settings. Sarka Lisonkova is investigating the impact of delayed childbearing on pregnancy outcomes and infants’ need for health care services in their first year. Using information on 200,000 births across the province from the BC Perinatal Database Registry, Sarka is comparing outcomes and health care utilization from births among 20 to 34-year-old mothers with those 35 and older. She is also reviewing the effect of risk factors for adverse pregnancy outcomes, such as smoking and fertility problems. The research could help improve prenatal counselling and risk assessment in prenatal care.

Early progression and detection of ovarian cancer

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.

Toxicogenetic analysis of valproic acid-associated hepatotoxicity in pediatric epileptic patients

Valproic acid is a drug that has been used successfully for the treatment of many types of seizures. Yet for some patients, the drug is associated with liver failure. Clinicians are not able to predict which patient will be at risk for this serious and sometime fatal side effect, but it is known that liver failure is more common in the very young patients and when the drug is used together with other anticonvulsants. Tony Kiang is studying the possibility that individuals could have a genetic predisposition for developing liver failure following valproic acid therapy. In his research project, Tony will be using advanced genomic technologies to test this hypothesis. Results from this research will help clinicians identify which patients are suitable to be prescribed valproic acid.