Acute lung injury is a very common cause of respiratory dysfunction among critically ill patients in intensive care units. It is caused by excessive inflammation in response to infection or major injuries. The widespread inflammation interferes with oxygen transfer such that patients with the condition often require the support of a mechanical ventilator. Despite advances in understanding how acute lung injury develops, the mortality rate from the condition has remained at 30 to 40 per cent. Dr. Sanjay Manocha is investigating whether genetic variations predispose some patients to excessive inflammation. Understanding which genes influence the development of acute lung injury could help identify those at high risk, and lead to more targeted therapies to treat this debilitating condition.
Year: 2004
Developing a computer simulation model for patient flow in health care system: access to coronary revascularization
In response to unprecedented pressure, the health care system has and continues to restructure systems of core delivery to achieve greater efficiency and effectiveness. While this points to the need for research to assess the effects of reorganization, there is a lack of such research, partly because analyzing the flow of patients through the health care system can be extremely complex. In previous research, Dr. Christos Vasilakis developed a computer simulation model capable of evaluating the interactions between the different streams of patient flow in a hospital department. This simulation model was also used to test an alternative hypothesis of the causes of hospital bed crises in England. Now he is developing a computer simulation model to evaluate the effects of proposed organizational changes at BC cardiac care centres that will affect patient access to revascularization procedures, which are used to improve blood flow to the heart. Hospital managers could use the completed model as a tool to manage patient access. Policy-makers could use the model to assess the impact of other proposed changes to the health care system to better inform how these changes should be made.
Probing the preparation and preprogramming of voluntary movements using startle in healthy humans and clinical populations
Every day people are required to make quick, voluntary responses to environmental signals, such as sound. The higher brain (cerebral cortex) has long been thought to control these movements by receiving and analyzing sensory information and coordinating responses. But Anthony Carlsen’s research has shown reactive movements can be stimulated more quickly with a loud, startling sound at 124 decibels. The research suggests it may be possible to pre-program these quicker responses and store them in the midbrain, the area that controls auditory and visual reflexes. Anthony is using Functional Magnetic Resonance Imaging (fMRI) to determine if there is brain activity with pre-programmed responses in the midbrain. He is also testing whether the startling sound triggers a midbrain response in people with Parkinson’s disease and those who become deaf following a stroke. Results from the study could provide insights about human motor control, the source of movement deficiencies caused by Parkinson’s, and potential treatments for people with Parkinson’s and cerebral deafness.
Structural characterization and inhibitor design of sialyltransfersases involved in lipooligosaccharide biosynthesis of Gram-negative pathogens
Bacterial resistance to antibiotics has become a major challenge in drug development. It is thus necessary to develop novel antimicrobial therapies to combat bacterial infection. Such development would require a thorough understanding of the mechanisms bacteria employ to cause disease. Campylobacter bacteria is the most commonly reported foodborne pathogen that cause acute gastroenteritis (inflammation of the stomach and intestines) and diarrheal illness in developed countries. Almost 99% of the reported cases are caused by a specific strain, called C. jejuni. Sialic acid (sugar molecules) on the cell surface of C. jejuni mimics human gangliosides and thus camouflages the bacteria from the host immune system. Cecilia Chiu is investigating the three-dimensional molecular structure of sialyltranferases, the class of enzymes responsible for the transfer of sialic acids onto the surface of Campylobacter. Cecilia aims to understand the mechanism of these enzymes and to develop molecules that inhibit the enzymes from sialylating the bacterial cell surface. This research could ultimately lead to the development of new therapeutic inhibitors against this common human pathogen.
The development and function of self-specific CD8+ CD44high T cells
About 38 percent of women and 41 percent of men will develop cancer during their lives. These staggering numbers highlight the need for new preventive measures and treatments for cancer. The human immune system is capable of eliminating pre-cancerous cells before they get a chance to grow. Salim Dhanji is researching how this process occurs. He is focusing on the development and function of a subset of T cells that control the immune system and fight infection. Salim aims to determine the conditions that maximize the ability of these cells to kill cancer cells. He ultimately wants to develop a strategy for using the body’s own immune system to fight cancer.
Functional modulation of N-methyl-D-aspartate receptors (NMDARs) by mutant huntingtin
Huntington’s disease (HD) is a hereditary, degenerative brain disorder that gradually diminishes movement and memory. HD has no cure and there are no treatments that prevent or slow the disease. Symptoms appear in middle age, with death usually occurring within 20 years as cells in specific parts of the brain slowly die or stop functioning properly. Mannie Fan is investigating the function of the huntingtin protein that causes HD, and also the molecular mechanisms that underlie development of the disease. Studies show that the death of brain cells associated with HD may result from too much activity in molecules called NMDA receptors, which normally facilitate brain cell communication. Mannie is investigating the underlying mechanisms that contribute to this increased activity. The research could help explain why people with the huntingtin protein develop HD and possibly lead to novel strategies for treating or preventing the disease.
Computational prediction and analysis of subcellular localization of bacterial proteins
Jennifer Gardy’s research is directed at predicting the location of proteins in disease-causing bacteria that could be targeted as potential vaccines or antibiotics. Jennifer developed PSORT-B, a software program that examines the biological features of proteins to predict where they most likely reside. It is the most precise software currently available for this purpose. Using data mining techniques that help establish relationships and identify patterns, Jennifer is fine-tuning the software to make it more accurate in predicting protein locations and functions. She is also developing modified versions of the program for specific groups of bacteria. Her aim is to make PSORT-B the leading software program for identifying vaccine and antibiotic targets.
Identification of novel genetic alterations in Lung Carcinogenesis
Lung cancer is the leading cause of cancer death in North America, with less than 15 percent of people surviving five years after diagnosis. The prognosis is poor because there are no symptoms in the early stages of lung cancer, which often results in the disease going undiagnosed until it is too late for established treatment to be effective. To increase the survival rate, diagnosis and treatment must occur earlier. Cumulative genetic changes are believed to cause cancer. Several genetic alterations have been identified in tumours, but the genes that lead to lung cancer remain unknown. Cathie Garnis is examining genetic changes in pre-malignant tumours to identify genes that play a significant role in lung cancer progression. The results could improve understanding of the biology behind lung cancer, and ultimately help clinicians diagnose the disease earlier and develop more effective treatments.
Relevance of aberrant activity in the temporal lobes during development to cognitive and behavioral impairment: a potential animal model of schizophrenia
People with schizophrenia experience symptoms such as delusions, hallucinations and disturbances in thinking, and often become fearful and withdrawn. Determining the cause of schizophrenia is difficult due to the heterogeneous nature and complexity of the disorder. Current theories suggest abnormal development in brain regions that regulate movement, emotion, speech, behaviour, learning and memory may cause schizophrenia. John Howland is studying whether altered interactions involving dopamine and glutamate — chemicals that carry messages between brain cells — can result in behaviour that is consistent with schizophrenia. This research could provide support for theories that developmental abnormalities cause schizophrenia.
Role of yo T cells and HMG-1 in staphylococcal toxic shock syndrome
Superantigens are secreted toxins from some kinds of bacteria that stimulate a massive and damaging immune response in the body, causing a number of diseases. For example, TSST-1 is a superantigen that can cause toxic shock syndrome which may lead to multiple organ failure and often death. Shirin Kalyan is studying how the immune system responds to superantigens at the cellular level. Superantigens activate between 5 to 30 percent of all T cells (white blood cells involved in fighting infection). This ability to stimulate such a large pool of immune cells leads to a massive inflammatory response. In contrast, conventional antigens activate less than .01 per cent of T cells. Shirin is investigating whether a particular type of primodial innate T cell can influence the immune response that causes toxic shock syndrome. The findings could lead to more effective treatments for toxic shock syndrome and other immune disorders caused by superantigens.