Tumour suppressor genes, such as ING1, help regulate normal cell growth by encoding proteins that inhibit abnormal proliferation of cells. Dr. LeAnn Howe is studying the molecular properties and function of ING1 proteins to understand the processes that lead to the development and growth of tumours. Research has linked ING1 proteins to modification of histones, the main protein component of chromatin, which makes up our chromosomes and genes. Evidence suggests that defects in regulation of chromatin structure may improperly activate or silence genes, leading to disease. Dr. Howe is examining the way ING proteins interact with chromatin to determine whether the proteins can modify chromatin. This research could help explain the role of ING1 genes in cancer development and contribute to new cancer therapies.
Program: Scholar
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.
Intracellular calcium stores as master regulators of pancreatic beta-cell survival: studies on transplantable human islets and knockout mice
Canada has a growing diabetes epidemic, which costs the Canadian health care system an estimated $13 billion annually. More than two million Canadians have the disease, and by 2010, the number is expected to increase to three million. Diabetes is also a major health problem worldwide. Although diabetes can be treated with insulin, a cure for this devastating disease remains elusive. All forms of diabetes are associated with the loss of functional pancreatic islet cells. However, very little is known about the underlying factors controlling how and why pancreatic islet cells die. Dr. James Johnson recently discovered important networks of molecules that control survival of islet cells. For example, one such network includes the RyR2 protein, which controls the release of calcium in the cell, and the calpain protein, which can split other proteins in response to increased calcium. Dr. Johnson is comparing the role of this survival network to other molecular networks to investigate how pancreatic islet cells die. The research could lead to better therapies for diabetes, including more successful pancreatic islet transplantation, a promising experimental treatment that depends critically on the continued survival of the donated cells. The findings could also improve understanding of other diseases where calcium is involved in cell death, such as heart failure, Alzheimer’s disease and stroke.
Studies on rational treatment of Parkinson's disease
Parkinson’s disease is a chronic, progressive disorder that affects about 100,000 Canadians, at an annual cost of more than $2.5 billion. The disease involves loss of both brain cells and chemicals that modulate communications between brain cells – causing not only motor symptoms of tremor, stiffness, and slow movements but also cognitive and behavioural changes. Conventional drug therapy for Parkinson’s disease replaces dopamine in the brain. Although most motor deficits usually improve after therapy, more than 50 percent of patients (particularly those in the later stages of the disease) may develop difficult problems, such as involuntary movements, dementia and psychosis. Dr. Chong Lee is studying neural mechanisms of these complications, which are resulting from the disease itself or the chronic use of Parkinson’s drugs. Dr. Lee is also evaluating the effectiveness of neuro-protective treatment, a strategy to prolong the survival of injured cells and slow the progression of Parkinson’s disease. He ultimately aims to develop strategies to treat dementia and behavioural symptoms of the disease and to reduce or prevent treatment-induced complications in patients with Parkinson’s disease.
The role of insect immune peptides in limiting disease transmission by vectors
Vector-borne diseases – diseases spread to humans by insect vectors – pose serious health problems worldwide. Malaria, transmitted by mosquitoes, kills 2-3 million people a year; Lymphatiic filariasis, transmitted by mosquitoes, afflicts more than 100 million people; African sleeping sickness, spread by tsetse flies, affects up to 500,000 people each year, most of whom die within two years of infection; Chagas Disease, transmitted by kissing bugs, is found only in the Americas and affects 30 million people and results in premature heart attacks. In North America, West Nile virus, spread by mosquitoes, has expanded to most regions. Insects have a potent immune system that kills most pathogens (disease-causing organisms). A major component of their immune response is the production of small proteins that kill many bacteria, viruses and parasites. Dr. Carl Lowenberger is studying these immune peptides to identify ways to reduce disease transmission to humans, and to determine if these antimicrobial peptides could be used to treat human infections. Many pathogens have developed resistance to antibiotics. Immune peptides isolated from insects in this research could provide a new source of antibiotics to overcome drug resistance.
Contribution of the ubiquitin/proteasome pathway to coxsackievirus-mediated myocarditis
Myocarditis, an inflammatory heart disease caused by the coxsackievirus, can lead to a dilated (enlarged) heart, which can result in sudden heart failure. A heart transplant is the only treatment for this condition. The proteasome is a cellular garbage collector that accumulates and destroys unwanted or damaged proteins. Ubiquitin is a molecule that latches onto damaged or mutated proteins and flags them for destruction by proteasomes. In earlier research, Dr. Honglin Luo showed that blocking the ubiquitin/proteasome pathway prevents the coxsackievirus from producing proteins, which may affect the ability of the virus to replicate. Now Dr. Luo is further investigating the effect of the ubiquitin-proteasome pathway on replication of the coxsackievirus and development of myocarditis. The research could confirm that inhibiting the pathway limits virus replication and prevents abnormal protein degradation, which could lead to new treatments for myocarditis that reduce progression of the disease to heart failure.
Role of the budding yeast kinetochore in chromosome segregation and checkpoint response
Cells must accurately duplicate their chromosomes (genes in the cell’s nucleus) and segregate them equally to daughter cells for proper cell growth and division. Errors in segregation results in cells with abnormal numbers of chromosomes (aneuploidy), which can lead to birth defects, Down’s syndrome and cancer. Cells have developed safeguards to ensure chromosomes are accurately segregated. A region of each chromosome called the centromere is bound by kinetochore proteins which attach to spindle microtubules, tiny fibres that pull newly separated chromosomes to each side of a dividing cell. If any mistakes occur in spindle attachment, kinetochore proteins signal the spindle checkpoint machinery, which delays segregation until the defects are corrected. Using yeast as a model, Dr. Vivien Measday is studying how kinetochore proteins attach to spindle microtubles and communicate with the checkpoint machinery. The research will improve understanding of chromosome segregation and could lead to treatments for diseases caused by abnormal numbers of chromosomes.
Psychoeducation in bipolar disorder: determining the effects of psychoeducation upon recurrence and quality of life in first episode mania patients
More than half a million Canadians suffer from bipolar disorder, a chronic psychiatric condition that causes repeated episodes of depression and/or elation. The condition significantly disrupts social and work lives, with high costs to the health care system. Although medical management of bipolar disorder has improved, many people have repeat episodes requiring frequent hospitalizations, and 15 percent of patients commit suicide. Research on the disorder is beginning to focus on treatments involving psychoeducation as well medication. This approach is designed to provide education about bipolar disorder and its treatment, promote early detection of symptoms, encourage regular sleep-wake cycles and social routines, enhance self-monitoring, and improve stress management skills. Dr. Erin Michalak is studying whether psychoeducation can improve quality of life for patients who have experienced their first episode of elated mood (mania). The research could determine whether psychoeducation helps to prevent relapse, reduce symptoms, improve adherence to medication, and improve ability to function socially and at work. The findings could be used to develop early intervention programs for people newly diagnosed with bipolar disorder.
Health Research of Vulnerable Urban Populations
Up to half of all Canadians with HIV also have hepatitis C, with co-infection highest among injection drug users. Dr. Anita Palepu is researching the impact of drug and alcohol use among people co-infected with HIV and hepatitis C on their adherence to HIV treatment and on treatment outcomes. Dr. Palepu, who focuses on health and social problems faced by vulnerable urban populations such as drug users and homeless people, is also examining the role of addiction treatment in clinical outcomes. In a related project, she is conducting a quality of life study with vulnerable populations such as injection drug users, homeless people and street youth to assess the effectiveness of interventions intended to improve their lives. Dr. Palepu is also part of a national network of researchers evaluating the effects of programs designed to prevent homelessness, or help people exit homelessness, on the health of those considered “hard to house.” The research could inform health and social policies and ultimately help improve the health of vulnerable urban populations.
Identification of circulating cells with a myogenic potential
Degenerative diseases have an enormous economic and social impact on BC’s aging population. In the long term, identifying cells that could regenerate organs damaged by degenerative diseases could revolutionize how these conditions are managed. Care could shift from expensive, lifelong drug treatments to therapies that permanently restore organ function. Research suggests that bone marrow contains stem cells (precursor cells that have the ability to develop into cells specific to types of tissues) capable of repairing damaged tissues in adults. To efficiently use stem cells, however, the cells responsible for tissue repair must be identified from among the many cell types present in bone marrow. Dr. Fabio Rossi is identifying bone marrow cells that repair damaged muscle, exploring their characteristics and investigating how they repair damaged tissue. Findings could lead to therapies that efficiently restore organ function.