Dr. Cheng-Han Lee, MD, PhD

Topic: Dedifferentiated and sarcomatous mullerian cancer – development of precision preclinical models to facilitate precision oncology

Summary: Cancer frequently displays cellular differentiation that recapitulates the tissue type it originates from, and across different organs, there is a remarkably consistent association with the degree of differentiation and the aggressiveness of the tumor. In the most extreme forms, a cancer can become completely undifferentiated such that it retains minimal to no phenotypic evidence of epithelial differentiation (dedifferentiated/undifferentiated carcinoma) or a cancer can transdifferentiate across from epithelial to mesenchymal cellular lineage (carcinosarcoma/sarcomatous carcinoma).  Dedifferentiated/undifferentiated endometrial/ovarian cancer exemplifies such a phenomenon. Secondary to genomic inactivation of core SWI/SNF complex protein and epigenetic shift, a well differentiated clinically favorable endometrioid-type cancer transforms/dedifferentiates into a highly aggressive undifferentiated cancer. Mullerian carcinosarcoma occurs when a TP53-mutated high-grade mullerian cancer undergoes sarcomatous transformation and a significant subset of these tumors carry genomically hardwired amplification involving receptor tyrosine kinases. We will discuss these improved molecular understandings and how they led us to develop patient tumor-derived precision preclinical models to facilitate therapeutic development in these aggressive types of gynecologic cancer.   

Biography: Dr. Lee is an associate professor at the Department of Laboratory Medicine and Pathology and is the current Sawin-Baldwin Chair in Ovarian Cancer Research at the University of Alberta. Dr. Lee received his MD-PhD degree and Anatomic Pathology residency training from UBC. The current research focus of his laboratory is on the genetics and biology of aggressive gynecologic cancer, and he has applied various next generation sequencing methods and high-throughput assays to gain novel insights into these tumors, including the most aggressive subtypes of uterine cancer such as dedifferentiated endometrial cancer and carcinosarcoma. Dr. Lee currently has over 160 peer-reviewed publications and a number of book chapters, including chapters in the latest WHO classification of female genital tumors. Clinically, he is a consultant pathologist at Royal Alexandra Hospital with a diagnostic focus on gynecologic oncology/pathology. 

Dr. Jessica Dennis, PhD

Topic: Genetic risk for major depressive disorder and loneliness in sex-specific associations with coronary artery disease

Summary: In this presentation, Dr. Dennis will discuss how the subjective feeling of loneliness is affected by genetics. Dr. Dennis will talk about how we used large-scale biobanks to: 1) conduct a genome-wide association scan of loneliness; and 2) to identify associations between polygenic risk for loneliness and cardiovascular disease, an association that was stronger in females than in males.  Moreover, although loneliness and depression often co-occur in individuals, we found that the genetic variants that predisposed people to feel lonely uniquely increased the risk of cardiovascular disease, while those that predisposed people to feel depressed did not. Dr. Dennis will also present follow-up work on the genetic contribution to sex differences in trajectories of depressive symptoms in Canadian adults as they age, using data from the Canadian Longitudinal Study on Aging.

Biography: Dr. Jessica Dennis is an Assistant Professor in the Department of Medical Genetics at the University of British Columbia, and an Investigator at BC Children’s Hospital Research Institute. A genetic epidemiologist by training, Dr. Dennis applies computational methods to large-scale genomic and population health data to identify the basis of human health and disease. She uses a life-course perspective to understand how genes and environment contribute from conception onwards to variation in disease susceptibility, response to treatment, and recovery, so that we may develop precision, patient-centered care. A primary goal of her research is to elucidate the biological mechanisms underlying psychiatric conditions, which vary considerably in their manifestation across the life course, and across males and females. Dr. Dennis completed postdoctoral training at Vanderbilt University Medical Center in Nashville, Tennessee. She holds a PhD from the University of Toronto, where she was a fellow in the interdisciplinary CIHR-STAGE Program (Canadian Institutes of Health Research Strategic Training for Advanced Genetic Epidemiology).

Dr. Mohammad R. Akbari, MD, PhD

Topic: Population-based screening for hereditary breast and ovarian cancers

Summary: Currently, there are three major clinical gaps in offering genetic testing for hereditary breast and ovarian cancers: 1) It is usually offered to patients after they have been diagnosed with cancer; 2) It is often offered to patients when their treatment has been completed and the test results cannot be used for their treatment; 3) It is not offered to all individuals who are at risk for hereditary cancer. The long-term solution for addressing all these gaps is to have a universal population-based genetic test for hereditary breast and ovarian cancer screening.

Biography: Dr. Akbari is an associate professor at the Dalla Lana School of Public Health, University of Toronto (U of T), and a scientist at Women’s College Research Institute (WCRI), Women’s College Hospital (WCH). He is also an adjunct faculty member at Institute of Medical Science, faculty of Medicine, University of Toronto and the director of the Molecular Genetics Research Laboratory at Women’s College Hospital. Dr. Akbari’s research interest is in studying genetic susceptibility to cancers, including breast, ovarian, esophageal, colon, pancreas and prostate cancers. This includes identifying new genes responsible for hereditary cancers, defining the role of known cancer genes, and individualizing cancer treatments for patients carrying a genetic mutation. One of his most recent works published in American Journal of Human Genetics identified ATRIP as a novel breast cancer susceptibility gene. Another key focus of his research program is to incorporate our current knowledge of cancer genetics into population strategies for reducing cancer burden by improving the current models of offering genetic screening for hereditary cancers. The Screen Project co-led by Dr. Akbari studies the feasibility of population-based screening for hereditary breast and ovarian cancers in Canada