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.

Courtesy of YFile.

https://magazine.yorku.ca/issues/summer-2019/the-big-o/

FOR MANY women, late-stage ovarian cancer is usually an automatic death sentence. But new breakthrough research at York University may give hope to those afflicted by the deadly disease.By honing in on the body’s complex internal systems involved in the development of ovarian cancer, York Research Chair and Faculty of Science Professor Chun Peng and former grad student Mohamed Salem (PhD ’18) have uncovered the pivotal role played by a small tumour-promoting molecule in those patients with the disease.“Our study provides strong new evidence to support a tumour-promoting role of miR-590-3p in ovarian cancer,” says Peng, who supervised the research investigation that focused specifically on epithelial ovarian cancer (EOC), the most common and deadliest form of the illness. “We also identified a gene, FOXA2, as a target of miR-590-3p, providing several important lines of evidence to support the idea that FOXA2 inhibits tumour growth in ovarian cancer.” A microRNA, miR-590-3p naturally exists in our cells. However, its increased presence in the body may indicate that ovarian cancer has struck, explains Salem, who collaborated on the five-year study with researchers from York University, the University of Ottawa and the American University in Cairo. 

Lowering that level can also help regulate the tumour progression and development, potentially resulting in a cure

Funded by the Canadian Institutes of Health Research and the Canada Foundation for Innovation/Ontario Research Fund, the findings were recently published in the peer-reviewed scientific journal Cancer Research. 

Significant is the discovery that “miR-590-3p levels are higher in the blood of ovarian cancer patients when compared to women with benign gynecological disorders,” says Salem, adding that the level of this microRNA is higher in more aggressive tumour tissues compared to less aggressive ones.

“Measuring the level of miR-590-3p could potentially allow for early detection of the disease without the need for invasive procedures like surgery. Lowering that level can also help regulate the tumour progression and development, potentially resulting in a cure.” 

While more work still needs to be done, the importance of this discovery cannot be underestimated. 

Ovarian cancer is a leading killer of women with gynecological cancer in the developed world, having a five-year survival rate of just 44 per cent.

The mortality rate is high mainly because ovarian cancer is often hard to detect at an early stage. Symptoms generally are vague and elusive, and advanced screening tests tend to be inconclusive or non-existent. That’s why so many women continue to be afflicted. 

An estimated 2,800 Canadian women will be diagnosed with ovarian cancer this year, and approximately 1,800 of them will die, according to the latest statistical data released by Ovarian Cancer Canada. 

But despite ongoing research to find a cure, early detection and effective treatments at later stages of the disease remain the only means for a long-term remedy to ovarian cancer.  

“The privilege of working in one of the York University labs, with cutting-edge advanced technology and a solid commitment and determination to make changes in people’s lives, lie at the core of our work,” Salem says. “The aim of our original research is to net results to benefit many.”

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Nantel Bergeron, professor in the Department of Mathematics and Statistics, Faculty of Science, was awarded a Tier 1 York Research Chair in Applied Algebra.  Bergeron is one of the pioneers in the development of the theory of combinatorial Hopf algebras that serve as a conceptual laboratory in which researchers can understand and solve complex problems from other areas of science and mathematics. His research program will help to better understand the complexity of algorithms in computer science and mathematics and bring further insights into super-symmetry of nature.

Ellen Bialystok, Distinguished Research Professor in the Department of Psychology, Faculty of Health, has received a Tier 1 Walter Gordon York Research Chair in Lifespan Cognitive Development. Her research examines the effects of experience on cognitive function and brain organization across the lifespan, with a particular focus on bilingualism as an example of an intense and prevalent experience. The award will support studies of patients with early Alzheimer’s disease to provide a more complete description of these dynamic changes and develop a training protocol based on compensation that will improve cognitive function for all patients.

Chun Peng, professor in the Department of Biology, Faculty of Science, was awarded a Tier 1 York Research Chair in Women’s Reproductive Health. Peng’s long-term goal for her research program is to understand the regulation of female reproduction and the mechanisms underlying the development of ovarian cancer and preeclampsia. Her proposed research will enhance the overall understanding of female reproductive health and reveal novel biomarkers for preeclampsia and therapeutic targets for ovarian cancer.

Stepan Wood, professor at Osgoode Hall Law School, has been awarded a Tier 1 Chair in Environmental Justice and Sustainability. His research program explores transnational sustainability governance schemes across many issue areas from a transdisciplinary perspective. His research program seeks to harness these interactions to empower marginalized interests and advance sustainability.

Chinese Canadian Legend recognizes and honours Chinese Canadians who have made significant contributions to the community and Canada through outstanding achievements in their field.

This year the Faculty of Science and Engineering presented researchers with Internal Research Awards to acknowledge the research achievements and dedication of various faculty members.

A world expert in the area of ovarian cancer and the molecular basis of complications in pregnancy, Professor Chun Peng from the Department of Biology is the recipient of the 2010 Established Researcher Award. Dr. Peng’s track record of awards and publications demonstrates the strong and superior research program and team that she has created at York University.

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Professor Chun Peng’s laboratory in the Biology Department has also been bursting with energy this summer as three NSERC USRA recipients have joined the group to pursue research projects in the area of cancer biology and fish reproduction.

Eilyad Honarparvar has been investigating an important protein called p27 that plays a protective role against cancer. Michele Taffs, joined the laboratory to investigate the role of certain chemicals in disrupting the reproductive system. Tanita Manchanda, will be exploring the role of miRNAs in placenta formation and eventually in cancer development and treatment.

Click here for the full article.

VP Research & Innovation Stan Shapson recently presented Chun Peng with a framed Premier’s Research Excellence Award certificate. The certificate was in recognition of her cutting-edge research in the areas of molecular endocrinology and female reproduction, especially regulation of ovarian and placental functions.

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