We all start as a single cell, which divides and eventually forms the body. A great deal of cell communication goes into making decisions about this body plan. My research examines how cells communicate with one another during embryonic development. The body plan is set up by organizing centres, or groups of cells that dictate signals to other parts of the early embryo. Two centres have been identified in mammals: the anterior visceral endoderm (AVE) coordinates the development of the head, and the node arranges the trunk into front, back, left and right. The way these organizing centres control growth of the embryo, and the cell-to-cell signalling involved in the process, are poorly understood. The same signalling systems used in creating an embryo break down during cancer. Ultimately, if we can identify what happens under normal circumstances, we can better understand what goes wrong with signalling pathways during the development of cancer or congenital defects. The results of my research also have implications for stem cell research. Stem cells have the potential to differentiate into various types of cells. If we can determine the signals that cause particular cells to become liver, brain or kidney cells during embryonic development, researchers should be able to cue stem cells to differentiate into specific cell types.
Archives: awards
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Prevention of falls and hip fractures in the elderly through biomechanics
Falls are the number one cause of injury-related deaths and hospitalizations in Canada. Among the elderly, falls account for 84 per cent of all injuries and about 23,000 hip fractures annually. Reducing the frequency and severity of these injuries is a critical national health priority, and one that my research team is approaching from several angles. In one approach, we are using laboratory experiments and mathematical modeling to study age-related changes in posture and balance along with strategies for avoiding injury in the event of a fall. In another approach, we are determining how movement patterns and risk for falls are affected by physiological factors, such as muscle strength and vision, and by behavioural factors, such as risk-taking tendencies. On the applied side, the team is working to develop devices such as hip pads, compliant floors and exercise programs to help prevent fractures. This combination of basic and applied efforts should lead to the development of innovative and effective techniques to prevent falls and fall-related fractures in the elderly.
Brain and behaviour: mechanisms of human attention in patient and healthy populations
Attention problems are a major source of disability associated with a wide range of disorders, including autism, stroke and schizophrenia. In British Columbia alone, hundreds of millions of dollars are spent each year by the health system for the treatment and rehabilitation of people with disorders of attention. And this does not take into account the additional costs for the education system or the toll on patients and families. I am studying the brain mechanisms underlying our attention processes and comparing how these processes affect perception and action in healthy children and adults, and those who have attention disorders. My research team is using behavioural and neuropsychological assessments, combined with advanced imaging technologies, to reveal brain processes involved in different attention tasks and behaviours. New knowledge about how the brain works in these activities will help in understanding and possibly developing better treatment and rehabilitation options for people with attention disorders.
Family influence in pediatric chronic pain and disability
Up to 15 per cent of school-aged children and adolescents suffer from chronic pain conditions such as recurrent headaches and abdominal pain. Children with chronic pain frequently miss considerable amounts of school, do not participate in athletic and social activities, and suffer depression or anxiety. The family plays an important role in influencing how children learn to deal with pain, but little is known about how this learning occurs. My research will identify how families influence children’s responses to pain. I will compare studies of children between the ages of eight and 15 with chronic pain and disability with pain-free children and their parents. The research will examine how families interpret pain symptoms, how parents make decisions about their children’s complaints of pain, parents’ thoughts about their children’s pain, and parent-child behaviour during pain episodes. In addition, I am studying how health care providers and parents assess pain in children and the tools that we use with children to measure pain. My research will also explore the relationship between sleep disturbances and chronic pain in children, an area of research that has been overlooked until now. The results of these research studies will help family members and health care providers better manage children’s pain, and will help improve treatment and prevention of disabling pain in children.
Suicide and self-injury as a response to radical developmental and cultural change in First Nations youth
Young people kill themselves in heartbreaking numbers, and intended and unintended self-injuries are the leading causes of death among our youth. However tragic this is when viewed in the large, the rates of suicide in certain First Nations communities are even higher – in some cases hundreds of times higher – and arguably the highest in the world. I am working to identify both individual and cultural factors that might help reduce the horrendous toll. Previous research has shown a strong link between suicidal behaviours and disruptions in the usual process by which adolescents develop their self-identity. It has also revealed that among First Nations communities, the risk youth run for suicide turns very much on the extent to which different bands have succeeded in reconnecting to their own cultural pasts. My research is directed at understanding the ways cultural differences during the course of identity development help or hinder young people’s ability to insulate themselves from such risks. By understanding the implications of these differences and working out ways of sharing them with various First Nations Communities, it may be possible to assist these communities in reconstructing cultural practices that, once recovered, may serve to better insulate their youth from self-injury and suicide.
Role for postsynaptic protein complex assembly in synapse development
Neurons (nerve cells) in the brain and central nervous system transmit signals to each other across connections called synapses. Glutamate is the primary neurotransmitter (messenger) that nerve cells use to send signals across these synapses to induce action in the brain. Glutamate enables the brain to develop and language to be learned. Without synapses that allow the chemical signal’s transmission from one nerve cell to the next, nerve cells will not be able to communicate with each other. Other neurotransmitters carry inhibitory signals to reduce activity in the brain. My research has shown that the post-synaptic density protein (PSD-95) stimulates the formation and maturing of the synapses that release glutamate, and increases the release of this neurotransmitter. Members of the PSD-95 family are involved in the development and organization of receptors that are clustered on the receiving side of the synapse. I am investigating how PSD-95 proteins regulate receptor clustering at synapses. This research is important because the number of receptors regulates the strength of the message: the more receptors, the stronger the message. We want to gain a better understanding of how receptors accumulate at synapses, and how changes in this process may underlie long-term changes in synapse structure and function associated with learning and memory. If we can determine how to change the number of receptors, we can permanently enhance the signals received in the brain, which could improve learning and memory function. Also, by understanding how synapses are formed and how neurotransmitter receptor clustering is regulated, we may figure out how to rescue abnormalities in synapse formation and function associated with several neurological diseases such as Alzheimer’s, mental retardation, schizophrenia and epilepsy.
Neurobiological and treatment studies in mood disorders
The treatments currently available for bipolar disorder and major depression are effective in relieving symptoms in only about 70 per cent of the patients. Furthermore, some patients have difficulty tolerating the side effects of these medications. In my lab, we are using Positron Emission Tomography (PET) scans to examine the levels of brain chemicals serotonin and dopamine in people with these mood disorders. Serotonin and dopamine control our emotions, sleep, appetite and energy, all of which are altered in patients with mood disorders. We are studying how these brain chemicals are altered and where changes in the brain occur, so we can develop new treatments that target these areas. Our research to date suggests that one type of serotonin receptor may be important in treating depression. In addition, I have set up a Canadian consortium on bipolar disorder (also known as manic depressive illness), which includes experts on bipolar disorder from all major Canadian universities. The consortium has recently received more than $2 million of funding from the Canadian Institutes of Health Research to examine the optimal length of therapy with novel antipsychotics and the effectiveness of psychotherapy and psychoeducation. We will also be pooling resources to examine how people with bipolar disorder respond to existing treatments compared to their outcomes with new treatments. We will be able to gather extensive data from all the sites to assess the effectiveness of different therapies. Given that many patients with bipolar disorder have problems with memory and concentration, we will study whether these symptoms are part of the illness and if early treatment can diminish them. My goal is to discover what brings on these symptoms and develop new treatments that improve patient outcomes and quality of life.
Analysis of prostate cancer progression using functional genomic approaches
In the early stages of prostate cancer, tumour growth is regulated by male sex hormones, called androgens. In treatment, androgens are removed to shrink the prostate tumour. However, the results of this therapy are usually temporary as surviving tumour cells become independent of androgens for growth and survival. I am investigating the genes responsible for this transition. To analyze these genes in a high throughput manner, I have created a Microarray Facility, the second of its kind in Canada. In the Facility, we can put up to tens of thousands of genes at a time on a single microscope slide. With this technology, we can now do experiments in a few days that would have taken years not long ago. We are comparing normal tissue to early and late tumours, and examining which genes are associated with tumour development. This research will identify the genes that cause prostate cancer, and how genes are turned on and off as the cancer progresses. We can use the information to predict when prostate cancer will occur, prevent its onset and develop new treatments that target the cancer-causing genes. In addition, we are investigating the effects environmental contaminants and dietary factors may have on the development and progression of prostate cancer.
Hepatitis A virus infections among children in British Columbia: Is routine vaccination needed?
Hepatitis A is a viral disease that causes inflammation of the liver. Once contracted, there is no treatment. Adults and older children with the disease usually suffer for four to ten weeks, and the symptoms include jaundice, fatigue, abdominal pain and fever. Young children usually have mild, symptom-free cases that go unrecognized, but can transmit the virus to people of all ages. The BC infection rates for hepatitis A virus have exceeded the national average for more than a decade. Yet a safe, effective vaccine has been available since 1994. The vaccine is currently only given to high-risk groups, and most cases reported by physicians come from these groups. I am investigating the risk of hepatitis A for children in two areas of BC that consistently report high infection rates. The study will determine whether universal childhood immunization is warranted. We can gauge risk for hepatitis A by testing saliva for antibodies to the virus, which would indicate a past infection. Our research team has tested about 800 randomly selected grade nine students. Students also filled out a questionnaire on potential risk factors. We are analyzing this data to identify why the hepatitis A rates may be higher in these areas and whether the scope of the disease is broader than reported cases indicate. If we find high rates of past infection, routine vaccination may be warranted. If low rates are found, the results will provide reassurance that existing sanitary measures are adequate to protect local children.
Gonadotropin-releasing hormone (GnRH) in reproductive biology and medicine
The long-term goal of my research is to understand the multi-faceted role of gonadotropin-releasing hormone (GnRH), the primary regulator of the reproductive process. Our brains release GnRH to the pituitary gland, where it stimulates the synthesis and release of the gonadotropin hormones that regulate gonads (ovaries and testes). My research has shown that GnRH also affects cell function in the ovaries and placenta and the hormone may play a role in controlling estrogen and progesterone production. GnRH has a role in both normal ovarian physiology and in the development of ovarian cancer. Ovarian cancer is a major cause of death, but little is known about the way it develops. We are seeking new knowledge that will help us understand the role of GnRH in the development of ovarian cancer, which should lead to more effective treatments in future. We also know GnRH affects the successful implanting of an embryo to establish a pregnancy and the formation of placenta, but that process is not well understood. My research will help explain the causes and process of fertility. Synthetic GnRH compounds are often used in different areas of reproductive medicine, such as fertility and sterility, ovulation control and assisted reproduction. This research will provide a better understanding of the cellular and molecular effects of these compounds and should improve clinical applications as a result.