Research: 2017 – Avalon (Kao)

Project Title:
Analysis of the interaction between the MYC oncoprotein and Pygo2 chromatin effector in prostate cancer
Investigators:

Kenneth R. Kao, Memorial University of Newfoundland

 

Dr. Ken Kao received his education and training in cancer research from the University of Toronto, the Marine Biological Laboratory in Woods Hole, MA, U.S.A., and the University of Cambridge, U.K. He completed an NCIC fellowship at the Mount Sinai Hospital in Toronto and subsequently joined, in 1993, the Faculty of Medicine at Memorial University of Newfoundland. Dr. Kao is presently full Professor in the Terry Fox Cancer Research Labs of the Division of Biomedical Sciences, where he runs a cutting-edge research laboratory studying the molecular and cell biology of cancer at Memorial University. He is also director of the IHC cancer testing laboratory at Eastern Health. He has published numerous internationally peer-reviewed original research articles and book chapters. His research has been and continues to be supported by research grants and contracts totaling more than $3.5 million from the Canadian Institutes of Health Research, the Cancer Research Society, The Canadian Breast Cancer Foundation, and most recently from funds generated by the Motorcycle Ride for Dad administered through the Dr. H. Bliss Murphy Cancer Foundation. Dr. Kao serves on national boards and committees dedicated to
responsible research funding in the biomedical and cancer field.

Project Abstract:
Prostate cancer is the most common non-­skin cancer in men. It can take years to progress and most patients die of other causes. But in some, prostate cancer is more aggressive and can be rapidly fatal. Identifying aggressive prostate cancer requiring immediate attention is critical for patient management. One factor in prostate cancer is the myc gene, which when deranged, can make it aggressive. We have found a novel chemical synergy between deranged myc and a protein called Pygopus2, which we think is exploited by actively growing cancer cells. Understanding this mechanism provides necessary information to design new therapies.
Scientific Abstract:

Background:
Our research has shown that elevated levels of the Pygo2 chromatin effector in prostatectomies portend poorer outcomes. We recently identified a novel, Wnt-independent interaction between the myc oncoprotein and the Pygo2 chromatin effector that drives broad sets of genes associated with cancer cell proliferation. Wnt gene aberrations and epigenetic activation leading to elevated Myc protein levels in tumors are prognostic for poor performance as well. We hypothesize that Pygo2 is utilized by myc for prostate tumour progression. We will analyse how Pygo2 interacts with Myc in prostate cancer.

 

Objectives:
1) Determine genome-wide association of Myc and Pygo2 in prostate cancer by ChIPseq
Sheared chromatin extracted from PrEc(normal), 22Rv1, LnCaP and PC-3 cells will be immunoprecipitated with Myc and Pygo2 antibodies and associated DNA sequenced to determined genes responsive to Myc:Pygo2 transcription

2) Perform ChIA-Pet analysis of prostate cancer cells to determine 3D organization of Myc:Pygo2 transcription complexes
Using the ChIPseq information, we will determine the genome 3 dimensional chromosomal organization regulated by Myc:Pygo2 transcription. Expertise, Experience and Resources: Our research team has the required expertise, resources in the Terry Fox Labs, and proven track records in advanced molecular,
biochemical and bioinformatics approaches.

Impact on prostate cancer patients:
The identification of gene sets that correlate with aggressive prostate cancer will be of enormous benefit to patients as they will assist in preparing a treatment plan. The results of this project are fundamental to the development of novel strategies for rational drug design that will add to, or enhance the current armamentarium of treatments for aggressive prostate cancer available to patients and their caregivers.