Research at The Biomedical Research Centre

Immunity and Infection, Inflammation, Regeneration: their impact on health and preventative, effective, regenerative medicine

The BRC is a leader in research on the processes through which our body defends itself against infections and restores the function of tissues damaged by infection or injury.

“Inflammation” is the immediate reaction of the body to injury or infection. We experience inflammation whenever we have had a sore throat, a splinter, or a sprained ankle and recognize it by the characteristic pain, swelling, redness and heat in the part of the body that is affected. Inflammation begins when damaged tissues release specialized chemicals and messenger proteins called “cytokines”. The cytokines attract white blood cells out of the blood and into the damaged tissue. In the tissues, the white blood cells battle the invaders and dispose of damaged tissues, setting the stage for stem cells to repair the damage and restore function. The stiffness you feel after exercise, or the pain and swelling associated with a broken bone, are all due to inflammation, and are part of the healing and regeneration response. At BRC, we study the formation and function of white blood cells, and the cytokines and other signals that regulate their entry and exit from the blood, as well as the stem cells that regenerate muscle, bone and cartilage.

“Immunity” is a system of specialized white blood cells that protects us from infectious diseases. The immune system learns from an encounter with a particular infectious agent, so that if we encounter it again, our inflammatory response is accelerated and toxins or microbes are neutralized before they do harm. We can duplicate this specific immunity against many but importantly not all infectious agents with specific vaccines. Vaccination is a triumph of medicine that has eliminated killer diseases like diphtheria, small pox or polio. However, there are many important diseases -like TB, malaria, HIV-1, human cytomegalovirus (HCMV), hepatitis C and enteric diseases that kill many children globally- for which vaccines have not been developed. A better understanding of how the immune system works is necessary if new vaccines are to be developed. BRC scientists are studying how the different components of the immune system defend against gastrointestinal infections and HCMV, as well as cancers, with a particular focus on how white blood cells migrate to the sites of infection and how immune responses are started and regulated.

“Regeneration” occurs normally in some tissues in the body –like the blood, skin, or the lining of the gut. In all of these instances, new tissues are generated continuously from stem cells that reside in adult tissues. Much of the pioneering work on adult tissue-specific stem cells was done on the stem cell that generates the red and white blood cells and the cells of the immune system. Application of the methods and strategies developed in study of the stem cells that give rise to the blood and immune system to other tissues has led to the identification of similar stem cells in tissues like the brain, breast and muscle. Repair and regeneration after injury or disease occurs easily in some tissues but in others –like cartilage of the joints, or the islets of the pancreas destroyed in diabetes, is ineffective. There has been a rapid increase in knowledge about how stem cells that have the potential to make any type of cells can be generated and about how different tissues can be generated from these cells. Stem cells have the potential to be used to generate new neurons damaged by stroke or Parkinson’s Disease, new muscle cells in hearts damaged by heart attacks, or new cartilage destroyed by arthritis. However to use stem cells optimally, we need to know to understand how stem cells behave and how they are affected by inflammation and repair responses. BRC researchers are studying how blood, nervous tissue, muscle, fat, bone and cartilage are generated.

DISEASES CAUSED BY DISTURBANCES IN IMMUNITY, INFLAMMATION, AND REGENERATION

White blood cells make powerful chemicals and enzymes to battle infections and dispose of damaged tissues. These weapons or tools can damage healthy tissues. For this reason, nature has evolved mechanisms that tightly control inflammation, but occasionally these safeguards fail resulting in diseases that can be chronic and devastating. These include many diseases which cause a significant burden and for which current treatments are inadequate.

Rheumatoid arthritis, juvenile diabetes, asthma, lupus, inflammatory bowel disease and multiple sclerosis. One cause of a chronic destructive inflammation is an immune response against a component of the body itself. This “auto-immunity” results in a chronic destructive inflammation that damages healthy tissues like the joints, insulin-producing cells, bronchial tubes, gut and brain in rheumatoid arthritis, juvenile diabetes, asthma, lupus, inflammatory bowel disease and multiple sclerosis. BRC scientists are studying new approaches to the treatment of rheumatoid arthritis, asthma, inflammatory bowel disease and multiple sclerosis.

Heart and vascular disease, Alzheimer’s disease, obesity and adult-onset diabetes. Chronic inflammation and autoimmunity also underlay important diseases usually considered to be caused by “metabolic “ problems like heart and vascular disease, Alzheimer’s disease, obesity and adult onset diabetes. Treatments designed to limit inflammation are showing promise for treating some of these diseases. BRC scientists are using their expertise in inflammation research to study new ideas on Alzheimer’s disease, obesity and adult-onset diabetes.

Cancer and leukemia. The immune system can help in controlling the growth of many cancers. However, it is now known that some cancers depend on inflammation, exploiting its ability to stimulate the production of new blood vessels, and using inflammatory cytokines to support their own survival, growth and spread. Cancer is also related to regeneration and repair. Thus, cancers of many tissues have their roots in genetic changes in stem cells that normally repair and regenerate that tissue. Indeed, cancer has been described as a“wound that won’t heal”.

Knowledge of the fundamental mechanisms that control inflammation, repair and regeneration promises to provide targets for new anti-cancer drugs. BRC researchers are studying how the immune system can be mobilized to attack cancer as well as finding novel targets for new drugs. Candidate compounds for new anti-cancer drugs are being developed in collaboration with experts in drug discovery and development in the Centre for Drug Research and Development.