Atrial fibrillation (AF) is the most common heart rhythm disorder. With an aging population, the number of people with AF is expected to rise dramatically. People with AF are twice as likely to die, are five times more likely to have a stroke, can develop worsening heart muscle function, and have a lower quality of life. We have learned that a person's genetic makeup, or DNA, has a major impact on their risk of developing AF; but we have a limited understanding of why, or how to use this information to treat people in a safer and more effective way. People with AF first receive drugs to control their irregular heart rhythm. Even people who have procedures to treat AF are also prescribed drugs. This is particularly important in the group of patients who have persistent AF, who require electrical or chemical therapy to change their heart rhythm, as the success of surgical procedures in this population is well below 50%. Unfortunately our current drugs are generally ineffective, and can be unsafe, with little progress in drug development over the last two decades.
With these challenges in mind, the first goal of my research program is to identify and understand the genes that play a role in the development and progression of AF, and determine which are most common and most important in the Canadian population. To do this, I am gathering a biobank of AF patients and performing the largest scale detailed genetic testing in this population to date. I am also focused on understanding the effect that genes can have on the safety and efficacy of rhythm controlling drugs, and have already started a trial, funded by the Canadian Cardiovascular Society, that will link a person's genetic makeup to these important outcomes. I will then be able to take this large clinical and genetic data set to the laboratory where we have developed the unique ability to generate patient-specific stem cell disease models of AF. The ultimate goal of my research program is to directly tailor therapy for AF patients based on their genetic makeup, using information from clinical research and personalized disease modeling.
Dr. Julia Schmidt’s research investigates the neurophysiology of concussion (mild traumatic brain injury) in children and youth. Dr. Schmidt spent over 10 years as a clinician in brain injury rehabilitation (Australia and Canada) prior to engaging in research training in Australia. She seeks to better understand injuries in order to more effectively determine rehabilitation strategies.
Asthma is a chronic lung disease affecting more than 2.8 million Canadians. It is estimated that numbers may rise to 400 million globally by 2025, substantially increasing both human and financial costs.
Alzheimer’s disease (AD) is the most common cause of dementia. Unfortunately, there are no effective treatments for this devastating disease. The Alzheimer’s Society estimates that without new treatments, 1.4 million Canadians will be living with dementia by 2031.
Brain swelling is a major cause of death following insults such as stroke and traumatic brain injury. This condition is often caused by an underlying swelling of neurons in the brain, leading to cell death. We currently have limited capacity to replace these neurons, and therefore must find ways to reduce swelling-induced cell death. Recent evidence suggests that an ion channel protein, called Panx1, is involved in this process. Ion channels essentially act as conduits between cells and the external environment. These proteins pass important signaling molecules to co-ordinate cellular responses, such as cell growth, movement, or death.
Our heart beat is a complex biochemical event. It relies on electrical signals, which can sometimes be disturbed, resulting in potentially fatal cardiac arrhythmias. One of the key parts involved in the contraction of heart muscle is a small ion known as calcium. Just prior to the contraction, calcium rushes into heart cells and triggers the contraction. Having the right amount of calcium at the right time is key for regular heart rhythms; too much or too little entry of calcium can be potentially fatal. The different compartments within the heart muscle cell are separated by membranes, which form barriers for many molecules. The calcium ions required for contraction of the heart muscle cells must pass through special gates. The sites where it all happens are formed by highly specialized protein channels that can open and close, thus determining the amount and timing of calcium release from one compartment to another. The most important of these so-called “calcium channels” is a large protein called ryanodine receptor. The gene that encodes this protein is one of the largest known genes, with literally hundreds of mutations documented to be the cause of the arrhythmia in patients.
A substantial portion of the cancer burden worldwide is attributable to infectious agents (viruses or bacteria). Some of these can directly cause cancers, others can facilitate cancer development, and the rest may have no causative role but their existence can indicate the presence of a cancer or risk of developing one.
Inflammation is recognized as multi-cell network dysregulation with an immunological component. Among the many cell types involved in acute inflammation are macrophages, specialized phagocytes involved in many immune responses. These cells exist in different activation states dependent on their biological stimulus and are unknown to play either a target or anti-target role in the context of inflammation.