With an aging population comes an increase in a number of diseases and conditions of the eye. A recent advance in imaging – called optical coherence tomography (OCT) – provides a non-invasive way to create high resolution, cross-sectional images of inside the eye. OCT is particularly useful in providing these images of the retina, showing cross sectional images of the various layers with resolution equivalent to a low-power microscope and better than other imaging techniques such as magnetic resonance imaging (MRI).
A new technological development called Fourier Domain (FD) OCT provides these images much more quickly than existing systems. It has also been successful in creating three-dimensional images of the retina, which were previously not possible to obtain. However, clinical use of FD OCT is limited as it generates only an image of the eye’s structures, without providing any functional information about the biological processes at play.
Dr. Marinko Sarunic’s research builds on earlier work where he successfully combined FD OCT imaging with molecular contrast capabilities to provide functional information. He is now using this technology to determine its usefulness in retinal diagnostics, the study of disease processes, and the testing of new drugs and therapies. Development of FD OCT imaging techniques will help physicians better understand and manage ophthalmic conditions, through high resolution visualization and improved minimally-invasive, image-guided procedures.
Asthma is the most common chronic disease in childhood and continues to increase in prevalence in adults. Every day, lung airways are subjected to challenges that damage their lining, known as the epithelium. The accumulation of damaged epithelium is a common and consistent feature in those with asthma, suggesting that asthmatics are more susceptible to damage, or are less able to repair the epithelium, than people without asthma. While the epithelium normally protects the underlying tissue from noxious particles, epithelial damage may account for airway hyper-reactivity in asthma, and the chronic nature of the disease. Previously supported by an MSFHR Scholar award, Dr. Delbert Dorscheid is researching the role of glycosylated proteins – proteins that have a sugar or sugar chain added to them – in epithelial repair. These proteins appear on the surface of cells that mediate repair, and their formation heralds the start of cell repair. Dorscheid has identified a specific protein that’s linked to the beginning of this process. His goal is to observe any changes in the modification and regulation of this receptor in asthmatic airways and healthy airways, and determine how this may influence injury and repair of the airway. The overall objective is to better understand the differences in asthmatic airways to develop new treatment strategies to improve the quality of life of those who suffer from this disease.
Chronic inflammatory airway diseases include asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). Together, these conditions contribute to an enormous burden of death and disability worldwide. It’s estimated that 10 to 15% of 13- to 14-year-olds in Canada are asthmatic. COPD affects close to half a million Canadians 35 and older, currently ranking 12th worldwide as a cause of lost quantity and quality of life and projected to rank 5th by the year 2020. CF is the most common, fatal genetic disease affecting Canadian children and adolescents.
There is compelling evidence supporting a hereditary pattern to virtually all of the major inflammatory diseases. For example, more than 1,000 CF-causing gene mutations have been identified. Although some mutations are associated with less severe disease, patients possessing the same mutations often show great variation in disease severity and progression. Significant advances in molecular genetics make it possible to discover the specific genetic variants that determine individual susceptibility to these illnesses.
Dr. Andrew Sandford is investigating the genetic variants that cause susceptibility to asthma and COPD. He is also focused on the role of genetics in CF. He works with a unique group of patient families who have previously been involved in studies to establish the associations between their genetic variations and their disease symptoms. A better understanding of the causes of inflammatory airway diseases will contribute to better prevention and/or intervention measures and more efficient treatment strategies.
Hypertension (high blood pressure) has a direct link to aging and is a major risk factor for atherosclerosis (narrowing and hardening of the arteries over time), stroke, heart attack and chronic renal failure. All known cardiovascular diseases, including hypertension, have in common a disease called endothelial dysfunction. The endothelium is a layer of cells that line the cavities of the heart, as well as the blood and lymph vessels. With endothelial disease, these cells do not function as well. Aging is known to induce and aggravate endothelial dysfunction, suggesting that endothelial dysfunction is unavoidable. One of the hallmarks of endothelial dysfunction is a decrease in the synthesis and availability of nitric oxide, which promotes dilation or relaxation of the blood vessels. Under normal conditions, nitric oxide significantly contributes to resting vasodilator tone and works to maintain a smooth and healthy vascular endothelium.
Dr. Pascal Bernatchez has uncovered a novel molecular approach that increases endothelial function and nitric oxide availability in aged vessels, while young vessels remain unaffected by the intervention. This suggests that there may be a molecular cause for how endothelial dysfunction develops. Bernatchez’s research will contribute to knowledge about how this approach restores endothelial function in an age-specific manner, how it regulates blood pressure and how endothelial dysfunction occurs. The findings may lead to novel therapeutic avenues for the range of cardiovascular diseases characterized by endothelial dysfunction.
Although heart disease is a leading cause of death for men and women, sex/gender differences in the disease have only recently received attention. Evidence suggests there are sex/gender differences relating to prevalence, presentation, diagnosis, treatment and outcomes of heart disease, but little is known about the underlying causes. An emerging area of interest is the fact the magnitude of the sex/gender difference in outcomes following a heart attack (favoring men) is much greater among younger women and men than among older patients. Research in this area suggests that this difference persists even after adjusting conventional risk factors.
A leading investigator in the area of cardiac health outcomes, Dr. Karin Humphries has found in previous research that among women and men with chest pain but no evidence of heart disease, women’s outcomes are worse. Now she is focusing on two primary questions: why these women have worse outcomes than men, and what is the relevance of non-traditional risk factors, such as quality of life and psychosocial factors, in young women and men who present to hospital with a heart attack. The results of these studies will provide new knowledge about sex/gender differences and heart disease. Humphries aims to increase understanding of quality of life differences between young men and women who suffer a heart attack, which may help explain the different outcomes and help with the development of new strategies for diagnosis, treatment and support of women with heart disease.
Impulsivity is a characteristic of human behaviour that can be both beneficial and detrimental in our everyday lives. An impulsive decision can allow us to seize a valuable opportunity, or to make an ill-considered choice that we live to regret. High levels of impulsivity are not only considered socially unacceptable, but they are a key symptom in a range of psychiatric illnesses including bipolar disorder, attention-deficit hyperactivity disorder (ADHD), pathological gambling, personality disorders and substance abuse. Understanding the neurobiological basis of impulsivity could provide valuable insight into these afflictions and potentially lead to the development of new treatment and therapeutic approaches. Dr. Catharine Winstanley is exploring the role of different regions of the brain on aspects of impulsive decision-making and gambling. One of the most commonly-used measurements of impulsive decision-making in human volunteers is the Iowa Gambling Task (IGT), in which subjects try to accumulate points by choosing from options associated with varying net gains or losses. Winstanley successfully developed a model of the IGT for use in rats, allowing her to measure their cognitive processes. She is also determining whether changing levels of brain chemicals, such as dopamine and serotonin, can affect impulsive choice, and whether these chemicals activate similar molecular pathways in neurons that can alter brain function and behaviour.
Emotional processes and higher order executive functions are governed in part by interconnected neural networks that link the amygdala (a brain nucleus in the temporal lobes) to the frontal lobes. Drug addicts, particularly those abusing psycho-stimulants such as amphetamine or cocaine, show impaired cognitive function specific to these particular brain circuits. Recent evidence suggests that the brain regions comprising this circuit may be particularly susceptible to long-term neuro-chemical, anatomical and neuro-physiological alterations following repeated exposure to this kind of drug abuse.
Building on his research as an MSFHR Scholar, Dr. Stanley Floresco's multidisciplinary research program aims to clarify the alterations in brain circuitry that occur following repeated exposure to psycho-stimulant drugs. Behavioural studies will determine how repeated exposure to drugs of abuse in animals disrupt certain cognitive functions known to be impaired in stimulant abusers, such as behavioural flexibility and decision-making. Other studies will investigate how activity in these brain circuits is altered following repeated drug exposure and clarify the cellular mechanisms that underlie the associated cognitive impairments. Investigating the changes that chronic drug abuse creates in these circuits will provide important insight into the abnormal brain function that underlies drug addiction. This could lead to development of treatments for the cognitive dysfunction that occurs with chronic drug abuse.
Although there are large individual differences in recovery rates from alcoholism, little is known about the emotional factors that underlie these differences. Studies suggest that shame and guilt, two negative self-conscious emotions (emotions that require self-evaluations), may have divergent effects on a range of health outcomes. Specifically, shame promotes a range of negative outcomes, such as depression, whereas guilt has more positive effects, including empathy and high self-esteem. In addition, two distinct kinds of pride — “authentic” and “hubristic” — may also have divergent effects. Dr. Jessica Tracy is researching the influence of these four emotions on recovery from alcohol addiction. She is testing whether newly-sober members of Alcoholics Anonymous (AA) who experience guilt and authentic pride, rather than shame and hubristic pride, enjoy greater health and recovery benefits over time. Tracy is also testing whether the thought processes that promote these emotions contribute to health outcomes, and if so, whether specific self-conscious emotions account for these effects. This research is unique in its emphasis on self-conscious emotions, which may play an important role in addiction. The findings could lead to new treatment methods for clinicians, such as targeting these important emotions.
Cells in multi-cellular organisms such as humans are arranged in highly complex three-dimensional structures. The cells attach to their environment through cell adhesion proteins, which create a type of living scaffolding for the body. Integrins are an important type of cell adhesion molecule that attaches cells to tissues to provide structure within the body (bone, tendon, etc). Cell adhesion has varied and critical roles during animal and human development. Defective cell adhesion can play a role in a variety of disorders such as muscle degeneration, thrombosis, blood clotting disorders and cancer.
Dr. Guy Tanentzapf is exploring the mechanisms that regulate the activity of integrins, as well as the role of integrins in preventing muscle degeneration. He is studying cell adhesions with the powerful genetic and molecular tools available for the fruit fly, commonly used in genetic modeling. Understanding how cell adhesions are formed and maintained is key to understanding both normal development and disease processes where integrin function is disrupted.
Viruses are responsible for many of the world's most serious diseases. In Canada, viral infections remain the single most common reason that people seek medical attention. In order to spread infection, many viruses replicate themselves in the nucleus of their host cells. To accomplish this, they must transport their genome into the nucleus – a process known as nuclear trafficking. Today, many aspects of this viral replication and initial entry into cells are well understood at the molecular level. However, very little is known about how viruses deliver their genetic material into the nucleus. Interrupting the trip into the nucleus could prevent the virus from spreading. A detailed description of this process is an important step to developing anti-viral therapy.
Dr. Nelly Panté studies the mechanism by which viruses deliver their genomes into the nucleus of their host cells. In particular, she is focusing on two common and important viruses: Influenza A and Hepatitis B virus. To investigate the trafficking of these viruses, Panté uses a combination of structural, functional, biochemical, and genetic approaches. As well, she uses high-resolution electron microscopy to track the virus’ movement and entry into host cell nuclei. This work is critical for complete understanding of viral infections – not only for targeting viral illnesses, but also for their potential application in gene-delivery technology, such as in anti-cancer gene therapy.
