Research Location: University of British Columbia

More than two million Canadians have diabetes, a chronic metabolic disorder caused by the inability of the body to produce or properly use insulin. Obesity is a risk factor for developing type 2 diabetes, the most common form of the disease. Dr. Timothy Kieffer has uncovered links between leptin – a hormone that affects how the body manages and stores fat – and insulin producing beta cells of the pancreas, plus the liver, one of insulin’s target tissues. His research suggests there may be a defect in the interaction between leptin, fat, beta cells and liver cells. Using genetic engineering approaches, Dr. Kieffer is investigating the role of leptin in the development of diabetes and obesity, in the hopes of eventually developing novel therapeutic strategies to combat these debilitating diseases.

The cell is the basic unit of structure and function in the body. Many of the functions of cells are performed by particular subcellular structures called “organelles”. Acidity (pH balance) is important for organelle function and disruptions in this environment can lead to uncoordinated communication between brain cells, compromised immunity and uncontrolled cell growth or death. Dr. Masayuki Numata is studying the mechanisms for pH regulation in cells. Dr. Masayuki Numata and his research team have isolated ion transporter proteins that may regulate acidity inside organelles. Using biochemical, cell biological, genetic and immunological techniques, he is investigating how these transporters are delivered to the right destination when they are needed and how they are regulated by different factors. The research could ultimately increase understanding of the mechanisms by which brain cells transmit signals to each other and how disruptions in these signaling pathways cause damage leading to Alzheimer’s disease and other neurodegenerative disorders.

Glutamate mediates signaling between neurons (nerve cells) by binding to protein receptors. Over-activation of one type of glutamate receptor, NMDA, can result in damage to neurons. Dr. Lynn Raymond is researching how neuronal activity and cell proteins regulate NMDA receptors, with the goal of better understanding how irregularities or disruptions in regulatory pathways are implicated in damage associated with neurological disease. Dr. Raymond is especially interested in Huntington’s Disease. This inherited neurological disorder causes progressive neurological damage in specific brain regions leading to movement abnormalities, personality changes, psychiatric disorders and memory loss. Studies have suggested that over-activation of NMDA receptors plays a major role in this selective destruction of brain cells. Dr. Raymond is investigating interactions between mutant huntingtin (the protein produced by the Huntington’s Disease gene) and NMDA receptors to gain a more detailed understanding of the causes of neuronal death in Huntington’s Disease – research that may help in the development of new therapies for this incurable disease.

Neurons (nerve cells) communicate through a process in which one cell stimulates another with an electric pulse transmitted by secreting special chemicals called neurotransmitters into the synapse (gap) between the cells. Learning and memory are influenced by changes in the strength of these synaptic connections and by alterations in the excitability of neurons (how readily they produce an electrochemical response). Abnormalities in the regulation of neuronal excitability give rise to neurological diseases including epilepsy and psychiatric diseases such as schizophrenia. Dr. Brian MacVicar is studying two aspects of synaptic transmission: mechanisms that regulate neuronal excitability and mechanisms that influence synaptic plasticity (the ability of neurons to adapt the way they communicate with each other). In one series of experiments, he is examining cells that surround neurons in the brain to determine if they influence neuronal activity through the regulation of blood flow or other mechanisms. He is also studying how past synaptic experience modifies activity in dendrites, the part of the neuron that receives synaptic transmissions. This research into how brain activity is regulated will contribute to improved understanding of many aspects of neuroscience, including stroke, mental illness and learning and memory.

The transformation of the embryo from a mass of undifferentiated cells into a fully formed, functioning organism is a complex process. In early embryonic development, discrete buds of cells fuse to create a face. If proper fusion fails to occurs, the result is severe developmental abnormalities including cleft lip with or without cleft palate. The embryonic segments that form the face are similar in chickens and mammals. Using the chicken embryo as a model, Dr. Joy Richman is studying how the jaw is formed and what goes awry in the process to cause cleft lip. By investigating the mechanisms that designate which embryonic facial bud will develop as a particular facial feature and how appropriate growth is initiated at key times to form a face, Dr. Richman will identify genes and gene signaling pathways that underlie normal and abnormal development of the face and jaw. Such information is critical for improved treatment and prevention strategies for defects such as cleft lip.

Once organisms are fully developed, stem cells are the basis for replenishing cells that wear out or are otherwise destroyed in the normal course of living. Researchers are now looking for ways of identifying and manipulating stem cells to regenerate organs or tissues such as heart muscle, liver, brain or the surface of the lung and digestive tract that have degenerated due to disease. The most well studied stem cells to date, are hematopoietic stem cells, which are produced in the bone marrow and are the precursors from which all blood cells develop. Dr. Kelly McNagny’s laboratory discovered MEP21, a molecule that appears to have a close connection to stem cells since its activation correlates closely with the appearance of stem cells in tissues. This suggests that the molecule may be involved in stem cell production and the processes by which stem cells grow differentially to become a specific type of tissue. Dr. McNagny’s research has shown that MEP21 is required for survival – i.e., mice lacking the molecule die shortly after birth. He is now studying its role in activating adult stem cells, with the goal of finding new ways of purifying and using stem cells to regenerate tissues.