JUL 29, 2020 1:00 PM EDT

Using quantitative imaging microscopy to explore and target the molecular origins of cancer

C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Associate Professor, Department of Biochemistry & Medical Genetics, University of Manitoba and Senior Scientist, Research Institute in Oncology & Hematology, CancerCare Manitoba
    Biography

      Dr. Kirk McManus is an Associate Professor in the Department of Biochemistry and Medical Genetics at the University of Manitoba. He is also a Senior Scientist within the Research Institute of Oncology and Hematology (formerly the Manitoba Institute of Cell Biology) housed within CancerCare Manitoba. He received a BSc (1995) and an MSc (1999) from the University of Manitoba and moved to Edmonton, Alberta to conduct his PhD studies (1999) in Oncology under the supervision of Dr. Michael Hendzel. There he studied the regulation and dynamics of post­translational histone modifications and their influence on chromosome segregation. His post­doctoral studies were performed with Dr. Phil Hieter at the Michael Smith Laboratories in Vancouver, BC, where he utilized cross-species approaches to identify genes that regulate chromosome stability and characterize their impact on cancer development. Dr. McManus joined the University of Manitoba in June, 2009, and research team is focused on identifying and characterizing genes that regulate chromosome stability in various cancer contexts including colorectal and ovarian, and exploiting these characteristics to identify novel therapeutic targets. His team currently couples genetics, biochemistry and cellular biology along with innovative digital imaging microscopy to identify the molecular determinants of chromosome instability and exploit this information using synthetic lethal strategies.


    Abstract

    The identification of novel drug targets and the development of next generation therapeutic strategies remain elusive goals for cancer researchers. We believe that the aberrant molecular events driving cancer development and progression can be exploited to devise novel therapeutic strategies that are highly selective towards cancer cells. Chromosome instability (CIN) is a form of genome instability that induces ongoing changes in chromosome complements and thus, is a driver of cell-to-cell heterogeneity. CIN is prevalent in many cancer types and is associated with cellular transformation, intratumoral heterogeneity, metastasis, the acquisition of drug resistance and poor patient prognosis. Despite all these associations, the aberrant genes, proteins and cellular processes (i.e. molecular determinants) giving rise to CIN remain largely unknown. To expand our basic understanding of the molecular determinants of CIN and cancer mandated the use of single-cell approaches capable of quantifying the cell-to-cell heterogeneity induced by CIN. Accordingly, we created several quantitative imaging microscopy approaches and employed them to evaluate hundreds of candidate CIN genes. Here, we present these approaches and their application in the discovery and characterization of a subset of CIN genes with pathogenic implications for cancer. We subsequently discuss the use of additional quantitative approaches to identify novel drug targets that selectively target and kill cancer cells harboring defects in CIN genes. Collectively, our work provides novel insight into the pathogenic origins of cancer that is crucial to develop the next generation of drug targets aimed at better combating the disease.

     

    Learning Objectives:

    1. Define chromosome instability (CIN) and describe its relationship with cancer.

    2. Detail three quantitative imaging microscopy approaches used to identify CIN genes.

    3. Describe how quantitative imaging microscopy approaches can be used to identify novel drug targets.


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