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.
Research Location: Vancouver Hospital & Health Sciences Centre
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.
Low trauma arm fractures and osteoporosis: An early warning system
More than 1.4 million Canadians have osteoporosis, a chronic condition that causes bones to become fragile and fracture easily. Clinical trials have shown that lifestyle changes and early medical management can reduce osteoporotic fractures in high-risk people. Past studies suggest that many people over 50 years of age who suffer a minor fracture are at risk for osteoporosis. This is an ideal time for osteoporosis investigation. Yet these patients are most often treated for the fracture alone and not investigated for osteoporosis. The aim of Maureen Ashe’s research is to investigate whether educating patients and raising physician awareness about osteoporosis after a low-trauma fracture could improve the investigation rate and if necessary, enable more patients to receive preventative therapy. Preliminary results from the study indicate that after providing education to patients and physicians at hospital fracture clinics, a substantially higher number of patients were assessed for osteoporosis.
Bi-specific antisense and RNAi targeting of IGFBP-2 and IGFBP-5 as a novel treatment strategy for delaying progression and bony metastasis of prostate cancer
Prostate Cancer is the most common cause of cancer and the second leading cause of cancer death in men in North America. But removing the androgens (male sex hormones) that regulate tumour growth — the only existing therapy shown to prolong survival — only produces temporary remission. Surviving tumour cells usually recur, becoming androgen independent. To improve survival, new therapeutic strategies must be developed. Dr. Alan So is exploring a novel way to treat prostate cancer at the molecular level. He is observing how prostate cancer is affected by shutting down two common genes in prostate cancer cells: IGFBP-2 and IGFBP-5 (insulin-like growth factor binding proteins). These genes are essential for prostate cancer to grow and spread to the bones. His research is also examining the effect of combining this treatment with chemotherapy on prostate cancer cells. The ultimate goal is to develop a more effective treatment for prostate cancer that can be tested in clinical trials.
The role of the stem cell antigen, CD34, on mature murine mast cells
In earlier research supported by a MSFHR Masters Trainee Award, Erin Drew disproved theories that CD34, a cell surface protein, was specific to immature blood cells. She found CD34 on immature blood cells, but also on cells lining the blood vessels and on mast cells. Mast cells are known to play a pivotal role in allergic and asthmatic responses. Erin’s work now focuses on CD34’s function in mast cells and how the protein prevents inappropriate adhesion to other cells and tissues. These enquiries will increase new knowledge on how blood cells move around the body and how mast cells can invade tissues and respond to allergens. Ultimately, Erin hopes her work will lead to the identification of targets for the treatment of allergies and asthma.
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.