What is the link between obesity and heart failure? How can the most common and deadly form of ovarian cancer be stopped? How does the regulation of healthy cells under stress go wrong and cause diseases such as cancer and neurodegeneration?
These are the questions three Faculty of Science biology researchers, who recently received more than $2.27 million in Canadian Institutes for Health Research (CIHR) project grants, will tackle over the next five years.
Professor Chun Peng, along with co-applicants chemistry Professor Arturo Orellana, biology Professor Yi Sheng and chemistry Professor Derek Wilson, will develop ways to inhibit the growth and spread of the most common form of ovarian cancer, epithelial ovarian cancer (EOC), which could lead to targeted therapies for EOC patients. Professor Mark Bayfield will look at what goes wrong with the regulation process in healthy cells when they are under stress and how that can lead to cancer and neurodegeneration. Professor Gary Sweeney will try to figure out if excess fat is altering the structure and function of the heart, causing heart failure, and how.
“York is delighted to see professors Peng, Bayfield and Sweeney receive project grants from CIHR. To award these extremely competitive CIHR grants reflects a recognition of the excellence of York researchers in the biomedical and health research field,” said Interim Vice-President Research and Innovation Rui Wang. “These three projects are prime examples of how York researchers are focusing on improving health outcomes and bridging new knowledge and applications to improve the understanding, prevention and treatment of disease and injuries, and to provide healthier environments for individuals and communities.”
Peng’s project, “Development of novel ß-catenin inhibitors as potential therapeutics for ovarian cancer,” received a CIHR grant of $879,750.
Epithelial ovarian cancer – the most common form of ovarian cancer – has the highest mortality rate of female cancers. The low survival rate for women with EOC results mainly from an inability to detect the disease at an early, curable stage and from the lack of effective treatment for advanced cancer. The Wnt/ß-catenin pathway is known to play critical roles in cancer development, such as maintaining the cancer stem cells, promoting the spreading of cancer cells from the primary tumour into other organs and inhibiting the effectiveness of conventional chemotherapies. Peng and her team searched for novel inhibitors of this pathway and identified two compounds that have strong anti-tumour effects. The team will further characterize the effect of these inhibitors on cancer stem cells, tumour growth and metastasis, and see how these inhibitors disrupt ß-catenin signalling to exert their anti-tumour effects. They will also generate structurally similar compounds to identify molecules that have better drug-like properties. The research could lead to the development of novel targeted therapies for EOC. Since the Wnt/ß-catenin pathway is involved in the development of many types of cancers, the small molecular inhibitors Peng and her team develop will be useful for targeting a wide range of cancers.
Bayfield’s project, “Translational Control by the La and La-Related Proteins,” received a CIHR grant of $669,376.
Healthy cells have evolved several ways to respond to their environment and adapt to stresses. One critical way that cells respond to such cues is by controlling the cohort of proteins they synthesize, which allows the cell to adapt to new situations. However, dysregulation of these responses can lead to diseases like cancer and neurodegeneration. One class of factors known to have an important function in the control of protein synthesis is the La and La-related proteins. Dysregulation of function of the La and La-related proteins has been linked extensively to cancer and infection by viruses, but how this happens is not yet understood. In this proposal, Bayfield will identify the genes that rely on these factors, as well the ways in which they control protein synthesis. The research could lead to a substantial new understanding for many challenges to human health.
Sweeney’s project, “Investigating novel mechanisms of lipocalin-2 mediated cardiac dysfunction and their translational therapeutic potential,” received a CIHR project grant of $722,926.
Many reports have established a correlation between obesity and cardiovascular complications such as heart failure. A causative role of obesity, and the accompanying diabetes, is well known. Heart failure is a progressive problem, which occurs due to changes in the structure and function of the heart, yet the precise mechanisms responsible for regulating these changes in obesity remain to be determined. Given the escalation in the occurrence of obesity, it is imperative to focus on understanding the mechanisms linking excess fat tissue to alterations in the structure and function of the heart to help prevent heart failure and potentially enhance the understanding of how to protect against the progression of heart failure.
For more information, visit the CIHR Project Grant website.