Osteoporosis is a chronic condition whereby bones become fragile and individuals are predisposed to fracture. Osteoporosis may occur in all older people but it most frequently affects post-menopausal women. Worldwide, more than nine million osteoporosis-related fractures occur annually. Older Canadians sustain more than 24,000 hip fractures annually — which levies a substantial physical, emotional and economic burden on individuals and the health care system. By 2040, this number is expected to increase to 90,000 at a cost of $2.4 billion. The likelihood of a person sustaining a fracture is related to their bone strength and their propensity to fall. Bone strength is related to bone’s material and structural properties. Currently, DXA (dual-energy x-ray absorptiometry) is the most commonly used diagnostic tool to measure bone health. However this technology has limitations in that it provides a two-dimensional (2-D) representation of bone, a 3-D structure. Further, DXA does not capture the nuances of bone geometry and structure that underpin bone strength. Recently, a high resolution imaging system (the Xtreme CT scanner) was developed that is able to assess bone mass, geometry and bone microarchitecture. The extent to which this novel technology is able to predict bone failure is currently unknown. Thus, Sarah Braid will utilize state-of-the-art imaging techniques (X-treme CT and pQCT) to evaluate bone strength and its components – and most importantly – link these evaluative tools with the susceptibility of a bone to fracture. The results of her research will enhance our ability to assess fracture risk so as to prevent fractures in vulnerable populations in future.
Program: Trainee
Negotiating International Health Policy on a Local Level: HIV Positive Women and their Experiences with Infant Feeding in Vancouver, Canada
Medical research currently debates what infant feeding method should be recommended to HIV positive mothers. Studies indicate that antiretroviral treatment effectively reduces transmission of HIV through breast milk by approximately at least two-thirds by lowering the amount of HIV in the blood. However, Canadian health policy strongly discourages breastfeeding regardless of a woman’s HIV viral status after giving birth, and encourages formula feeding as the alternative. Avoiding breastfeeding may eliminate the risk of HIV transmission, but is “replacement feeding” with formula the safest most viable option? Francoise Guigné is interviewing physicians, health care providers, and educators, and women living with HIV in Saskatoon, a city reknown for breastfeeding promotion, about their recommendations and experiences with formula feeding. Preparing formula can be expensive and complicated. Guigné is assessing the social, cultural, economic and emotional challenges HIV-positive women face with replacement feeding, and, the international flows of health knowledge that doctors, health care providers and educators use to address these challenges. Compared to breastfed babies, formula fed infants suffer higher rates of diarrhea, respiratory, ear and other ailments. HIV-positive mothers must weigh these health risks against the risk of acquiring HIV through breastfeeding. Guigné’s research aims to identify and address any gaps in support services for HIV-positive mothers by improving the support networks, medical resources and counselling services currently available to them.
Identification of microRNAs, their targets and roles in human embryonic stem cells
Stem cells are a special variety of cells that can self-renew indefinitely and can become a multitude of cell types. Embryonic stem cells are the most versatile variety of stem cells and can potentially develop into any adult cell type. Many cancer researchers believe that in most (if not all) types of cancers, there is a population of cancer stem cells that actively sustain the production of cancer cells. A better understanding of stem cells is crucial in advancing knowledge of all cell types, including cancer cells. Before manipulation of embryonic stem cells can be explored as a method of treating disease, and before anti-cancer drugs that target cancer stem cells can be designed, there is a need to understand the genetic structure and the signaling pathways that maintain these cells. Ryan Morin’s research is directed at understanding how the regulation of gene expression differs between embryonic stem cells during their differentiation into other cell types. His particular focus applies new sequencing technologies to unravel the cellular complexity of the regulatory molecules known as microRNAs and their involvement in embryonic stem cell gene regulation.
Lentiviral-mediated RNA interference of the multifunctional cellular enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH): Impact on the hepatitis C virus life cycle
Hepatits C virus (HCV) causes chronic liver disease, such as cirrhosis (liver disease) and hepatocarcinoma (liver cancer), an irreversible condition that results in liver failure. There is no vaccine or drug available to prevent or treat this infection, which makes HCV the number one cause of liver transplantation in North America. Host proteins are involved in feeding and sheltering organisms such as viruses. Structural and functional studies revealed that a host protein, glyceraldehydes-3-phosphate (GAPDH) interacts with 3’ non-coding region (NCR) of the HCV genome. This multifunctional protein is also shown to associate with genome of several other RNA viruses, such as hepatitis A virus, hepatitis D virus, human parainfluenza virus type 3, and hepatitis B virus, but its function in the virus life cycle is uncertain. Independent of its glycolitic function, this multifunctional protein is also shown to play a role as an apoptosis mediator upon oxidative stress, and is shown to be essential in endoplasmic reticulum (ER) to Golgi transport. This suggests that GAPDH may be involved in several stages of HCV life cycle, such as regulation of translation and replication by interacting with HCV 3’NCR, modulation of liver damage from oxidative stress imposed by HCV encoded proteins, and formation of new virus partivles by budding of nascent HCV genome through the ER. Meera Raj is researching the biological role of GAPDH in the HCV life cycle, which may include regulating viral replication, facilitating viral assembly and modulating viral release from the host cell. In order to show that GAPDH plays a role in HCV life cycle, Meera has prepared human hepatoma (liver) cells showing reduction in GAPDH expression. Her next step is to study the effects of GAPDH reduction on HCV life-cycle. In order to find other host factors that may play a key role in the HCV life-cycle, she will use microarray to study changes in gene expression within HCV infected cells. Her study will provide insight into the HCV biology, host-viral interaction and may provide a potential new strategy for HCV treatment. Establishing GAPDH as a therapeutic target may also provide a broad base therapy for other infections, because targeting host proteins can affect the life cycles of many other viruses.
Acute lung injury: FasL, apoptosis and protection by erythropoietin
Acute Respiratory Distress Syndrome (ARDS) is a common catastrophic lung condition that complicates critical illnesses of many types, most commonly severe infections. In ARDS, the cells that line the airspaces of the lung are injured and die. As a result, the lungs flood with fluid, becoming stiff, scarred and unable to transport oxygen into the bloodstream. Half of all patients with ARDS die, and there are currently no specific therapies to treat the condition, other than to provide supportive care. Erthropoieten (EPO) is a natural hormone that regulates the production of red blood cells in bone marrow. Injecting EPO is an established and safe therapy for anemia in patients with kidney failure, and it has been shown to protect against cell death in experimental models of stroke and heart attack. Patients with critical illness in the intensive care unit have abnormally low levels of EPO in their blood, leading to the hypothesis that low levels of EPO in the lung might contribute to cell injury and death in ARDS. Dr. Ruth MacRedmond’s research is the first to study the presence and activity of EPO in the lung. She is examining the ability of EPO treatment to prevent cell death caused by infection and the protective properties of EPO treatment in preventing ARDS. This project will expand our understanding of the mechanisms of cellular injury and death in ARDS, and explore the potential of EPO to act as a novel and important therapy for this devastating disease.
Molecular Pathways Linking Socioeconomic Status, Stress Experiences, and Asthma Severity in Children
About three million Canadians have asthma, a chronic disease of the airways that causes shortness of breath, tightness in the chest, coughing, and wheezing. The prevalence of asthma among children in the developed world has been rapidly increasing, with up to one in four urban children affected. Research shows that stressful life experiences as well as low socioeconomic status have been linked to poor asthma outcomes in children. To date, few studies have examined the common underlying molecular mechanisms behind these links. Dr. Jutta Wolf is investigating how these two variables — stress experiences and socioeconomic status (SES) — can biologically influence asthma symptoms. Stress can cause immune cells to produce more “cytokine” molecules. Cytokines are proteins that stimulate or inhibit the activity of immune cells, which can aggravate asthma symptoms. Stress is also associated with the release of the hormone cortisol. Jutta is examining whether cortisol is incapable of suppressing a molecule called NF-kappa B, which causes immune cells to produce more cytokines in asthma patients, exacerbating their symptoms. This research could help care providers identify early signs of worsening asthma in children, so their condition can be better managed.
Prosopagnosia and the processing of familiarity, identity and the self
Brain injuries can have lasting detrimental effects on the way someone thinks and behaves. Prosopagnosia, a rare disorder that can result from brain injury, impairs the ability to recognize faces. Patients with this condition may have trouble recognizing family members, coworkers, and even their own face in the mirror. This disorder is debilitating because everyday interactions rely on being able to recognize people. For example, people usually act quite differently when speaking to their boss or their spouse. With her MSFHR award, Kirsten Dalrymple is studying how the healthy brain recognizes faces and how this function is impaired with prosopagnosia (sometimes known as face blindness). Certain brain activations occur when someone looks at a face. Dalrymple will record and compare how brain activations differ between people who have prosopagnosia and those who function normally. In addition, most people remember things better when there’s a connection to themselves, rather than a reference to something unfamiliar, like the face of a stranger. Dalrymple is investigating whether or not this “self-reference” ability is present in people with prosopagnosia, who may be unaware that they are looking at their own face in a picture, rather than the face of a stranger. Her findings could be used to help patients rehabilitate from, or compensate for, the effects of this disorder.
Bioinformatics of sequence indels: Novel applications for protein network analysis, drug target identification and drug development
Infectious diseases continue to be a huge threat worldwide. The effectiveness of current antibiotics is declining as many life-threatening bacteria have developed resistance to existing drugs, giving rise to the need for a new generation of antibiotics. An important factor responsible for emerging bacterial resistance is that conventional antibiotic drugs are designed to disable proteins on bacteria that allow it to infect host cells. These particular proteins mutate readily, which enhances their potential to develop resistance mechanisms against antibiotic treatment. An alternative strategy in antibiotic development would be to target “conserved” proteins – fundamental proteins that are resistant to mutations, because they perform essential functions that keep the bacteria alive. Michael Hsing’s research is focused on developing antibiotics that selectively target conserved and essential proteins in pathogens. To do this, he is investigating the important biological phenomenon of protein insertions and deletions (referred to as indels) and combining this approach with the latest computational tools to develop novel antibiotics that are more rapid and effective than the conventional approach. His goal is the development of an effective and economical method of developing antibiotic drugs to treat existing and emerging pathogens.
Cognitive, emotional, and behavioural implications of vicarious trauma
Everyone is exposed to stressors in their personal and work lives. How people evaluate and deal with these stressors determines how well they cope, which has implications for their immediate and long term health. Stress can also be less direct, the result of witnessing severe trauma suffered by others, such as the 9/11 attacks on the World Trade Center in New York and London subway attacks in 2005. Research has shown this “vicarious trauma” can also have a substantial impact on health, from post-traumatic stress disorder to depression and persistent worry. Rajiv Jhangiani is studying how individuals react when exposed to trauma indirectly. He is examining how people process information, react emotionally, and make decisions during their exposure to vicarious trauma. Jhangiani is assessing how certain factors influence this reaction and ability to cope, such as identifying with victims, the degree of uncertainty about the situation, information overload, and resilience. This information will help identify how individuals and health and social service providers can support healthy ways of coping with vicarious trauma.
Female sexual arousal disorder subtypes: Conceptualization, diagnosis and treatment
Sexual dysfunctions play a significant role in depression, anxiety, stress, and marital/relationship satisfaction. Female Sexual Arousal Disorder (FSAD) affects approximately 1/4 of women aged 18-59. However, there are no established treatments for this disorder, with drug therapy trials yielding inconclusive and contradictory results. Recently, researchers and clinicians have disputed the current classification of FSAD as it only involves impairments in physiological sexual arousal and ignores the subjective aspect that the majority of women report. As a result, experts in the field have proposed a new classification involving three specific FSAD subtypes. Building on her research as a MSFHR-funded Master’s student, Carolin Klein is conducting a series of three experiments using alternative modes of activating the sympathetic nervous system to extend and replicate previous findings on these subtypes of FSAD. Carolin aims to better understand sexual functioning and the relationship between physiological and subjective sexual arousal in women in order to improve treatments. If further research continues to support the delineation of FSAD into separate subtypes , it may explain why treatments that increase physiological arousal appear to have no, or only a minimal effect on subjective arousal, and vice versa. Accordingly, separate treatments will be needed depending on the FSAD subtype.