Research Location: University of British Columbia - Point Grey

Bilirubin is an abundant, reddish-yellow bile pigment found in mammalian tissues and serum. The pigment has long been regarded as simply a cytotoxic waste product that needs to be excreted, as bilirubin in high concentrations can cause neurological damage. In recent years, however, increasing evidence suggests that bilirubin may also have functional importance. In vitro studies have demonstrated that bilirubin is an antioxidant substance. Other studies indicate that bilirubin may be capable of modifying or regulating immune functions. At present, however, the potential biological activities and physiological role of bilirubin is not well understood. Yingru Liu is studying the antioxidant effect of bilirubin, and exploring other physiological functions that bilirubin may also possess. Specifically, he is using an animal model to investigate the potential protective role of bilirubin as it relates to multiple sclerosis, a disease in which oxidative stress by free radicals and immunological factors play important disease-causing roles. His work may characterize the bile pigment system as an attractive target for drug therapy in multiple sclerosis. In addition, his research may have an impact on guidelines for treatment of an excess of bilirubin (such as neonatal jaundice and physiological hyperbilirubinemia). It may also confirm the need and potential methods of treating abnormally low levels of bilirubin.

Bone marrow contains cells which infrequently contribute to the repair of numerous tissues and therefore holds tremendous potential for regenerating damaged tissues in adults. Conceivably, a simple bone marrow transplant could one day facilitate treatment of a variety of degenerative conditions such as muscular dystrophy or Alzheimer’s disease. However, researchers first must discover which bone marrow derived cells are involved as well as the mechanisms which guide the repair processes in order to increase its efficency to therapeutic levels. Michael Long is investigating this phenomenon utilizing bone marrow transplantation in mice. His research aims to identify the lineage and mechanism responsible for the generation of new tissue from bone marrow. Ultimately, Michael’s research will contribute to the development of novel therapeutic strategies that efficiently restore organ and tissue function.

While most people understand paralysis due to spinal cord injuries, they are less aware of the other consequences of these injuries. Damage to the spinal cord can also result in chronic pain, loss of sexual function, and loss of control of bodily functions, including control of the bladder and bowels. Loss of bladder control is particularly problematic because it frequently results in bladder infections requiring medication, and sometimes hospitalization. Because most spinal cord injuries (SCIs) do not involve a complete disconnection of the brain from the spinal cord, there is potential to make new connections in the spinal cord by stimulating neurons that survive the injury. Leanne Ramer is researching the potential for growth of uninjured neurons in the spinal cord to improve bladder function after SCI. She will examine bladder function in rats with SCI, with and without treatments to enhance growth of neurons in the spinal cord. The outcome of these studies may provide new avenues for exploring ways of improving bladder control and quality of life following spinal cord injury.

Spinal cord injury results in devastating, permanent consequences for the injured individual when the nerve cells that form the spinal cord and connect the brain to the muscles of the body fail to regenerate. One of the most promising therapies for nerve cell regeneration is transplantation of olfactory ensheathing cells, which are involved in our ability to smell and help nerve cells in the olfactory system to continually regenerate. Research has focused on the transplantation potential of olfactory ensheathing cells, which form a protective layer around nerve cells and also play a role in regulating their function. Restoration of some motor functions has been reported following transplantation of these cells, but the mechanisms by which this occurs is not understood. Further, only some spinal cord injuries respond to this treatment and the reason for that is also unknown. Miranda Richter is studying nerve cell growth in vivo and in vitro to determine the intrinsic differences between different tracts of the spinal cord in their responsiveness to ensheathing cells. This will enable her to understand what mechanisms are used by ensheathing cells to promote nerve cell growth. By dissecting the mechanisms of this action, her research may contribute to the development of a more effective treatment for spinal cord injury.

A healthy immune system constantly monitors the body, helping to detect and eliminate infected cells and those that become cancerous. This system is mediated by a group of molecules called MHC Class 1, which adhere to and present a sample of the contents of a cell for scanning by T cells. T cells are specialized immune cells that are programmed to recognize and destroy abnormal or infected cells. In auto immune disease, such as Crohn’s disease, Lupus and Rheumatoid arthritis, this system breaks down and the T cells kill both abnormal cells as well as healthy ones. Robyn Seipp is researching the role of a specific molecule within the MHC Class 1 assembly pathway called tapasin. This molecule assists in the assembly and determination of which proteins are presented to the T cells on the cell surface. Her research is examining two newly discovered variants of the tapasin molecule that appear to function differently. She is studying these variants of tapasin to determine their effect on how, when and where immune responses to various pathogens or tumours are made. Results from her research will help better understand how tapasin contributes to the body’s ability to mount immune responses to pathogens and cancers while avoiding autoimmune diseases. A better understanding of their function could have important implications for vaccine design and may lead to better application of generalized tumour therapy.

More than 2 million Canadians and 135 million people worldwide have diabetes, a chronic medical condition characterized by a lack of insulin (Type 1), or insensitivity to insulin (Type 2), a blood sugar-lowering hormone. Type 1 diabetes can be treated by transplantation of islets, which contain the insulin-producing cells, to patients, but use of this therapy is limited by the huge volume of islets required to treat all Type 1 diabetes patients. As a result, most continue to rely on insulin injections to help control blood glucose levels. Glucagon-like peptide-1 (GLP-1) is produced in the intestine and has numerous anti-diabetic effects. Clinical trials are currently investigating GLP-1 as a treatment for Type 2 diabetes. Other recent studies show GLP-1 also enhances the growth of islet tissue. As a 2003 MSFHR Trainee, Rhonda Wideman investigated the effects of GLP-1 on the growth and survival of transplanted islets to determine if GLP-1 reduces the amount of islets needed to treat Type 1 diabetes in transplant recipients. Now in a PhD program, Rhonda is examining the therapeutic potential of engineering islets to produce GLP-1. She is investigating whether islets in which GLP-1 production has been induced will indeed survive and function better following transplantation. This would reduce the amount of islets necessary for a successful transplant and enhance post-transplant islet function. Ultimately, Rhonda hopes her studies will contribute to improved islet transplantation protocols, which are more effective and less reliant on limited supplies of donor islet tissue.

Medical imaging techniques such as X-rays, CT scans and MRIs, are widely used tools for diagnosing injury and illness. These tools provide a “”picture”” of bones, organs, muscles, tendons, nerves and cartilage, including any abnormalities. A new and evolving imaging technique called positron emission tomography, or PET scanning, provides additional details by creating a three dimensional image or map of functional processes in the body. By injecting radiolabelled molecules into the bloodstream, and then tracing their path and interactions, researchers and doctors can observe and map metabolic activity within various organs of the body. Photodynamic therapy (PDT) which is used in the treatment of psoriasis and certain cancers is similar to PET scanning in that photodynamic molecules (photosensitizers) are injected into the bloodstream. When the tissue to be treated is exposed to special light, the photosensitizers are activated, leading to a destructive action which kills abnormal cells. Richard Ting’s research is focused on examining and developing novel molecules, with potential application for both PET scanning techniques and photodynamic therapy. He aims to design a new class of molecules that would expand the limited amount of agents that can be imaged during PET scanning. In addition, he is researching a new class of molecules that could be used to improve the processes involved in photodynamic therapy.