Dr. Kirk McManus
 Kirk McManus

Associate Professor, Department of Biochemistry and Medical Genetics
Senior Scientist,
Research Institute in Oncology and Hematology

Mutations in genes that cause genome instability are now recognized as significant genetic factors that drive tumor development. Genome instability is a hallmark associated with virtually all tumor types including both solid (e.g. breast and colon) and liquid (e.g. lymphoma and leukemia) and generally arises through 3 mechanisms; 1) Microsatellite Instability (MSI), which arises due to defects in DNA repair and results in a gene mutator phenotype, 2) CpG Island Methylator Phenotype (CIMP), which results in the epigenetic silencing of genes, and 3) Chromosome Instability (CIN), which results in numerical and/or structural defects in chromosomes. Chromosome instability is of particular interest because it associated with up to 85% of randomly arising colorectal cancers.

Chromosome instability is also associated with aggressive tumors, multidrug resistance to chemotherapeutics and poor patient prognosis. However, we believe that cancer cells with chromosome instability represent ‘genetically sensitized’ cells that can be selectively targeted. In fact, since chromosome instability is only contained within the tumor cells, we believe it clearly distinguishes cancer cells from normal surrounding tissues and thus will restrict killing to the tumor cells, minimizing many of the adverse side effects associated with many current approaches. Consequently, one of our main goals is to identify and develop the next generation of therapeutic strategies and drug targets designed to combat cancer.

Currently, our research team is highly focused on identifying, characterizing and exploiting the origins of cancer, whether it be colon, breast or ovarian. However, since chromosome instability is found in all tumor types, the results we generate using our colorectal cancer models, will be of general interest to virtually any tumor type.

We currently employ biochemistry, genetics, and cell biology to answer four critical questions;
1.  What are the genes that when mutated contribute to the development of cancer?
2.  Can we characterize the molecular pathways that are required to maintain chromosome
     stability?
3.  What is the contribution of chromosome instability to interval colorectal cancers, or tumors
     that rapidly arise after a clearing or negative colonoscopy?
4.  Can we identify new drug targets that exploit and selectively kill cancers with defects in
     specific genes that are normally required to maintain chromosome stability?

Biosketch

Contact Information:

204.787.2833
ON6010 CancerCare Manitoba
Kirk.McManus@umanitoba.ca
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