Analysis of nuclear and cytoplasmic Mcl-1 protein complexes

Tissues in multi-cellular organisms maintain a state of equilibrium (homeostasis) through a delicate balance between controlled cell growth and programmed cell death (apoptosis). Programmed cell death is required to remove superfluous, damaged or harmful cells. Uncontrolled cell growth can lead to cancer, autoimmune disorders and neurodegenerative diseases. The BCL-2 family of proteins tightly regulates the cell death process. Dr. Marc Germain is investigating their role in cell death. One of these proteins, Mcl-1, prevents cell death and also seems to have a role in controlling cell division. Dr. Germain is examining how different forms of this protein control the body’s equilibrium, which could improve understanding of how cancer develops and potentially lead to new anti-cancer drugs.

Identification and characterization of genes dysregulated by YB-1 during prostate tumour progression

Prostate cancer is the second leading cause of cancer death in men. While curable if discovered early, many men are diagnosed after the disease has metastasized (spread) to other parts of the body. At this point few treatments are effective. Androgens (male sex hormones) regulate prostate growth and development. Removing androgens is the most effective treatment for advanced prostate cancer. However, some cancer cells eventually adapt and become androgen-independent, enabling the disease to progress. The YB-1 protein regulates two genes involved in the progression of androgen independence. Using sophisticated DNA microarray technology, Dr. Susan Moore aims to identify additional genes regulated by this protein to learn how androgen independence develops. The findings could lead to earlier diagnosis and new treatments for prostate cancer.

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.

The roles of apoptosis and IGF-I in tendinosis of the rotator cuff

Physical activities involving repetitive strain can injure tendons, causing chronic pain and disability. Contrary to previous thinking, chronic overuse tendon injuries do not involve inflammation. Instead, these injuries primarily involve the breakdown and disarray of collagen, a structural protein that is the primary support for tendons as well as bone, cartilage and skin. Recent research associates chronic tendon injury with excessive apoptosis (programmed cell death) among tendon cells. Alexander Scott’s preliminary laboratory studies identified two stressful conditions that can cause the problem: repetitive mechanical strain and lack of oxygen. Now he is investigating the basic mechanisms of tendon degeneration, with the aim of discovering whether abnormal rates of cell death occur in real life models of tendon injury. Alexander is also testing whether IGF-1, a potent growth factor, can help tendons better recover from injury. The research could lead to new treatments for people who suffer from painful tendon injuries.

Molecular analysis of transplant recipients

One of the major problems for patients who have undergone heart or other transplants is the potential for the body’s own immune system to attack the newly introduced organ. As a result, patients must take large doses of immunosuppressive drugs daily to prevent rejection of the new organ, which the body perceives as foreign. Unfortunately, these medications interfere with normal immune response, which leads to a wide range of dangerous side effects, including higher susceptibility to infections and cancer. Dosage must be carefully monitored: not enough, and the body will begin to reject the organ; too much, and patients must deal with the serious side effects. The goal of Edward Chang’s work is to develop new genetic tests to predict exactly how much medication each individual patient requires to ensure the organ is accepted with minimal side effects.

Functional role of p33ING1 phosphorylation in cellular stress responses to DNA damage

The organization of DNA sequences within a structured framework is vital to maintain the stability of a cell’s genetic material. When DNA damage occurs and is left unrepaired, it can affect cell division and normal cellular functions and ultimately lead to cancer. Eric Campos is expanding previous knowledge generated in Dr. Gang Li’s lab around a tumour suppressing protein known as p33ING1. This protein has been found to play an important role in the cell’s response to ultraviolet radiation, enhancing the repair of UV-damaged DNA. Eric’s research focuses on the biochemical processes by which p33ING1 is activated. This work could lead to novel treatments for cancer, a disease caused by the onset of genomic instability.

The effect of early controlled mobilization interventions on early fracture healing in a simulated hand fracture-healing model

Each year, about 11,500 people in BC fracture bones in the hand, usually from an accidental fall, a blow or compression between objects. Treatment typically involves immobilizing the fractured hand in a cast or splint for up to four weeks, which is necessary to allow bones to heal, but can also lead to loss of function and the need for further interventions or rehabilitation. Some studies have shown that earlier controlled mobilization of the hand following a fracture could reduce the negative consequences associated with immobilization. But studies haven’t addressed whether this earlier intervention is safe or will improve function. Lynne Feehan is examining the safety of two methods for early mobilization to lay the foundation for future research into this potentially useful approach for reducing side effects and improving fracture healing.

Spine biomechanics in osteoporotic thoracic vertebrae: investigating the safety of manual therapy

People with spinal osteoporosis often suffer back pain that cannot be relieved by exercise or medication. Physiotherapists with advanced training can use manual spinal joint mobilization techniques, also called manual therapy, to relieve the pain. However, there are questions about how safe the therapy is and whether the techniques pose a risk of causing fractures. Meena Sran is using bioengineering techniques to determine if manual therapy creates a risk of fracture in people with spinal osteoporosis. Besides assessing the spine’s ability to resist fracture during manual therapy by determining the pressure required to fracture vertebrae, she is also examining whether or not x-rays and CT scans can detect these fractures. The study will provide insights into the safety of manual therapy and ultimately help improve treatment of back pain in older adults with spinal osteoporosis.

Development of a direct computer interface using descending motor potentials recorded from the spinal cord

A variety of devices are available for individuals with motor impairments, such as electrical stimulation systems for locomotion. But people with severe disabilities are often unable to control these devices effectively. Dr. Jaimie Borisoff, who has published research papers on neural regeneration in the journals Experimental Neurology and Molecular and Cellular Neuroscience, is researching assistive technologies to enhance quality of life for people with severe disabilities. Jaimie is investigating whether motor control information can be recorded directly from the spinal cord, since much of the intentional and logistical processing has already been performed in the brain before the signal pathway terminates at the spinal lesion. If so, this information could be used to create a control system that uses signals from the spinal cord.

The effects of a community-based exercise program on cognitive function and falls in older women with a history of falls: a 12-month randomized controlled trial

Falls are the most frequent cause of injuries and injury-related death in older people. Recent guidelines on preventing falls recognize cognitive impairment as a leading risk factor. People with cognitive impairment have 2.2 times greater risk for falls causing injuries and 1.7 times the mortality rate of older adults with regular cognitive function. Research on falls has not determined which domains of cognition — including attention, memory and perception — figure most significantly in this increased risk. Dr. Teresa Liu-Ambrose is investigating the specific dimensions of cognition most strongly associated with falls in older women. She is also examining the impact of a 12-month exercise program on these dimensions, and the relationship between changes in cognitive function and incidence of falls. Results from the study could contribute to the design of exercise programs to help prevent falls in older people.