Mantle cell lymphoma (MCL) is an aggressive cancer of the lymphatic system that is incurable with chemotherapy or radiation. MCL has a survival rate of approximately three years, with no long-term survivors. Ronald deLeeuw is studying the biology of this disease to learn more about how it progresses. He is focusing on secondary genetic alterations concurrent to a characteristic feature of MCL: the switching of a genetic segment from one chromosome to another (translocation), which results in uncontrolled growth of lymphatic cells and an unregulated growth signal. Using new technology that reveals previously undetectable genetic changes, Ronald is compiling a comprehensive list of secondary genetic alterations that could contribute to progression of MCL. The research could provide insights about potential targets in treatment of MCL.
Year: 2004
Assembly of Postsynaptic Protein Complexes in Hippocampal Neurons
Synapses, the connections that enable brain cells to communicate with each other, are fundamental to normal brain function. Studies suggest synapses form and mature quickly—in a few hours—but the molecular interactions that trigger this process in the central nervous system are unclear. Kimberly Gerrow is researching the molecular stages of synapse development in the hippocampus, a part of the brain involved in cognitive functions such as learning and memory. She is investigating the role of PSD-95 protein (postsynaptic density protein), in assembling molecules crucial for creating synapses. This could lead to improved understanding and treatment of neurological disorders that result from interruptions or abnormalities in synaptic development. The findings could also offer insights into ways of re-establishing functional brain connections that have been damaged by conditions such as stroke, Parkinson’s and Alzheimer’s disease.
Identification of alternative splice variants and changes in patterns of alternative splicing involved in cancer by bioinformatic analysis and expression studies
The Human Genome Project identified approximately 25,000 genes in human DNA, which was much less than expected. However, about 60 percent of these genes undergo alternative splicing, in which one gene is assembled from its component pieces in many different ways. This phenomenon enables genes to have incredibly diverse variations that represent hundreds of thousands of functional units. Malachi Griffith is studying how changes in certain genes due to alternative splicing may have an important role in cancer progression and could account for differences in the severity of the disease from one individual to another. Malachi is comparing large sets of data from genes in healthy individuals and cancer patients to determine if differences in gene forms help explain the causes of different cancers. Findings could contribute to improved diagnosis and treatment of cancer.
Myocardial regeneration with hematopoietic stem cells
Heart attacks are the leading cause of death in the industrialized world. Interest is growing in the use of stem cells to treat the irreversible damage caused by a heart attack. Recent studies have shown hematopoietic stem cells (HSCs), stem cells in the bone marrow, can form heart cells. HSCs are easy to obtain, avoid the ethical issues associated with embryonic stem cells, and their use in bone marrow transplants is well established. The major challenge facing the use of stem cell therapy to treat heart disease is cell survival after transplantation. Heather Heine is comparing different subpopulations of these cells to determine the optimal type to use for treating the heart, how best to administer the stem cells, and how to improve cell survival in the oxygen-depleted environment created by a heart attack. This research could contribute to more effective therapy for improving cardiac function and survival following a heart attack.
Modelling and simulating intra-cellular signalling systems in response to pathogen invasions by semantic networks
Organisms that cause disease use various strategies to create infection. Bacteria such as Mycobacterium tuberculosis invade cells in the human immune system. These bacteria manipulate the internal machinery of a host cell to enter and survive inside the cell. A cell contains many different types of molecules that interact in complex ways to control cell behaviours. Michael Hsing is studying these interactions to understand how bacterial invasions occur. He is using a computer method, called the semantic network, to simulate molecular interactions and cellular behaviours during bacterial invasions. The research could enable researchers to predict how cells respond in different situations, potentially leading to development of drugs to prevent and treat bacterial infections.
GLP-1 gene therapy for Diabetes
Diabetes is a chronic disease that affects more than two million Canadians and 135 million people worldwide. People with this condition are unable to maintain normal blood sugar levels due to a lack of, or insensitivity to, insulin, a hormone that regulates blood sugar levels. Current treatments include insulin injections or oral drugs that stimulate insulin release or improve insulin sensitivity; however, daily administration is required due to their short-term effects. Gene therapy represents an exciting approach in treating diabetes by providing a means to achieve automatic delivery of therapeutic hormones within the body. Glucagon-like peptide-1 (GLP-1) is an intestinal gut hormone with a variety of anti-diabetic effects. Initial clinical studies show that GLP-1 can stimulate insulin production and release. Corinna Lee is examining whether gene therapy could achieve automatic, long-term release of GLP-1 from cells within the body. This research could provide insights into a new method of diabetes treatment that could eliminate the need for daily injections or oral drugs.
Mechanistic investigations of Family 4 Glycosidases
Carbohydrates traditionally were thought to serve one role: reservoirs of energy for maintaining metabolism. In fact, they serve much more diverse and vital roles, including regulation of cellular activity. Vivian Yip is studying Family 4 glycoside hydrolases, a family of enzymes that break down carbohydrates in bacterial cells. These enzymes are part of a system that transports sugar molecules across the cell membrane and into the cell. Inside the cell, the enzymes cut the sugar into smaller pieces to provide food for the bacteria. Vivian is investigating the chemical mechanism of these enzymes, which will provide important clues to inhibiting the enzymes’ activity. Inhibition of these enzymes could restrict the food supply, which would cause bacterial cells to die. Findings from the research could be used to develop antibiotics to reduce bacterial infections with potentially few side effects since currently these enzymes are found only from bacterial sources, but not mammalian.
Role of apoptosis repressor with caspase recruitment domain (ARC) in attenuation of chronic heart transplant rejection associated with transplant vascular disease
More than 2,500 heart transplants are performed worldwide every year. Chronic rejection of the transplanted heart due to transplant vascular disease (TVD) is the greatest obstacle to long-term survival after the operation. TVD causes structural changes in the arteries, leading to blockage that restricts and ultimately cuts blood flow. Despite improvements in anti-rejection drugs, about 40 percent of heart transplant recipients develop the disease within five years. The protein ARC has been shown to prevent death of cardiac cells. Arwen Hunter is investigating the ability of ARC to prevent cell death in blood vessel walls after transplantation. In particular, she is looking at the ways ARC inhibits cell death in blood vessels and ways of optimizing the delivery of ARC into heart tissue. The research could contribute to strategies for preventing organ rejection associated with transplant vascular disease.
Enhancement of melanoma chemosensitivity by adenoviral delivery of PUMA
Melanoma is an aggressive and lethal form of skin cancer that is increasingly prevalent among Caucasians. Although often curable if diagnosed early and surgically removed, melanoma tumors can rapidly metastasize (spread) to other parts of the body. Patients diagnosed with melanoma at later stages face a poor prognosis and survival rates averaging only six to ten months. Once it has spread, melanoma is extremely difficult to treat because it does not respond well to conventional cancer treatments such as radiation and chemotherapy. But the reason for this resistance is unknown. Most anti-cancer drugs induce apoptosis (programmed cell death) in tumor cells. Melanoma may have abnormally high levels of cell survival genes, making them difficult to kill with such drugs. Alison Karst is investigating whether introduction of the PUMA cell death gene into malignant tumors could overcome this problem and sensitize malignant cells to chemotherapy.
Assessing the utility of novel technologies to better characterize structure and strength in growing bone: an MRI and pQCT study
Each year in Canada more than 24,000 people will fracture hips due to weakened bones caused by osteoporosis. Current ability to predict risk of hip fracture is limited. Dual-energy x-ray absorptiometry (DXA) is used to assess bone density, but it shows a two-dimensional representation of bone, which is a three-dimensional structure. DXA is also unable to assess the structural properties of bone, which are a major factor in bone strength. Sarah Manske is evaluating whether two emerging technologies can accurately measure bone structure and strength. Magnetic Resonance Imaging (MRI) can measure cross-sections of bones to evaluate strength, without radiation exposure. Quantitative computed tomography (QCT) can assess bone in three dimensions. Sarah aims to develop a model integrating different imaging technologies to provide a more comprehensive picture of fracture risk. The information could be used to target preventative health strategies to help those at greatest risk of hip fracture.