Research Institute in Oncology and Hematology

Michael Mowat

Genetics of Tumour Cell Progression and Drug Response

Contact: Dr Michael Mowat PhD
Research Institute in Oncology and Hematology
5022-675 McDermot Ave
Winnipeg, Mb R3E 0V9
(204) 787-4139
Email: Dr Michael Mowat PhD

Apoptosis

One area of research in my laboratory is the study of programmed cell death or apoptosis, a form of cell suicide. As a result of genetic changes, cancer cells have a reduced or slowed ability to undergo apoptosis, which can also make tumour cells more resistant to anti-cancer drug treatment. To better understand programmed cell death, we have taken a genetic approach. Several mutant cell lines have been isolated that are defective in apoptosis. This was done by using a specially constructed virus that, after it infects a cell, integrates into genes and interferes with their function. After selection for drug resistant cells, the underlying genes disrupted by the virus are studied for their role in programmed cell death and drug resistance. By understanding the genetic basis of resistance to cell death, completely new treatments can be devised.

A gene that came out of these screens was the Dlc-2 (Deleted in liver cancer two) tumour suppressor gene. We are now studying the role this gene plays, along with the closely related Dlc-1 gene, in tumour cell progression and drug response. The Dlc-1 gene is found deleted in over 50 percent of breast, lung, liver and colon cancers. Also, the other normal copy of the gene is frequently silenced by promoter methylation. To study the role these genes play in the body, we have developed conditional knockout mouse models. With these mouse models, we can study the role the Dlc genes play in lung, and breast cancer spread through the body and anti-cancer drug response.


Team Members

  • Pratima Basak (Post-Doctoral Fellow)
    • Postdoctoral Fellowship from Research Manitoba / CancerCare Manitoba, 2012-2013, 2014-2016.
  • Nicole Wilkinson (Graduate student)
    • Breast Cancer Society of Canada Hope Scholarship 2015
    • Research Manitoba - University of Manitoba Graduate Student Scholarship 2016-2017


Awards and Professional Service

Grant Review Committees

Cancer Research Society, member Panel D, Metastasis and Tumour Progression 2010-11
National Cancer Institute of Canada, Panel J: Pathology and Tumour Markers 2005-08

Editorial Boards:

Canadian Journal of Physiology and Pharmacology, Associate Editor 2011-

Department Service

Biochemistry & Medical Genetics Graduate Affairs Committee, 2007-2013
Member, PhD Candidacy examination committees, 2005-09, 2011-13
Recruitment Committee-Assistant Professor 2010
Administrative Service - RIOH Associate Director (acting) 2011- 2012
Executive committee 2000-13
Chair, CancerCare MB library committee 1996-present
Member, Space Committee 2000- present
Member, Genomic Centre for Cancer Research and Diagnosis User Committee 2000-present

Administrative Service - RIOH

Associate Director (acting) 2011- present
Executive committee 2000-11
Chair, CancerCare MB library committee 1996-present
Member, Space Committee 2000- present

Publications since 2010

PubMed Listed Publications
  1. Dlc1 interaction with non-muscle myosin heavy chain II-A (Myh9) and Rac1 activation. Sabbir MG, Dillon R, Mowat MR. . Biol Open. 2016 Apr 15;5(4):452-60. doi: 10.1242/bio.015859.
  2. The Deleted in Liver Cancer 1 (Dlc1) tumor suppressor is haploinsufficient for mammary gland development and epithelial cell polarity. Basak P, Dillon R, Leslie H, Raouf A, Mowat MR.. BMC Cancer. 2015 Sep 9;15(1):630. doi: 10.1186/s12885-015-1642-x.
  3. The Role of Dlc1 Isoform 2 in K-Ras2(G12D) Induced Thymic Cancer. Sabbir MG, Prieditis H, Ravinsky E, Mowat MR. PLoS One. 2012;7(7):e40302. Epub 2012 Jul 5.
  4. Duplication of sub-cytoband 11E2 of chromosome 11 is always associated with accelerated tumor development in v-abl/myc induced mouse plasmacytomas. Wiener, F., Schmalter, A.K., Mowat, M. R. A. and Mai, S. Genes & Cancer 1( 8): 847-858 (2010).
  5. The Dynamics of Cardiolipin synthesis post mitochondrial fusion. Xu, F., McBride, H., Acehan, D., Vaz, F., Houtkooper, R., Lee, R., Mowat, M. Hatch, G. Biochim Biophys Acta. -Biomembranes (8):1577-85. Epub 2010 Apr 29. (2010).
  6. Identification and characterization of Dlc1isoforms in the mouse and study of the biological function of a single gene trapped isoform. Sabbir, M.G., Wigle, N., Shauna Loewen, S., Gu. Y., Buse C., Hicks G.G., Mowat M.R.A. BMC Biology 8(1): 17-38 (2010).
Abstracts:
  1. Basak, P. Leslie, H. Dillon, R. Raouf, A.and Mowat, M.R.A. Role of the tumor suppressor gene DLC-2 in ERBB2 induced mouse mammary tumorigenesis and metastasis. Poster presentation: at AACR Tumor Metastasis conference November 30, 2015, Austin, Texas.
  2. Pratima Basak, Heather Leslie, Afshin Raouf, Michael RA Mowat. Role of the Tumor Suppressor Gene DLC-2 in ERBB2 induced mouse mammary Tumorigenesis. CancerCare Manitoba Research Day for Trainees in Clinical and Basic Medical Sciences, Winnipeg, Manitoba, Canada. May 8th, 2014.
  3. Pratima Basak, Heather Leslie, Afshin Raouf, Michael RA Mowat. Understanding the biological impact of conditional inactivation of DLC-2 in ERBB2 induced mammary tumor progression. 27th Canadian Student Health Research Forum 2014, Winnipeg, Manitoba, Canada, June 11th, 2014.
  4. Basak, P., Dillon, R., Leslie, H., Raouf, A. Mowat, M.R.A. Mammary gland development and epithelial cell polarity affected by the decreased expression of Deleted in Liver Cancer 1 (DLC1), a tumor suppressor gene. The Canadian Cancer Research Conference, Toronto, ON, C-18 pg. 125 Abstract book (Nov., 2013)
  5. Wanpeng, S., Leslie, H., Xu, F.Y., Wilkins, J. A., Lippert, D., Mowat, M. R. Hatch,G.M. The Interaction between Ceramide and the Deleted in Liver Cancer 2 Protein. Frontiers in Lipid Biology, Joint Meeting of the International Conference on Bioscience of Lipids (ICBL) and the Canadian Lipoprotein Conference (CLC) Banff, AB, Abstract 2371 pg 150, Sept. (2012).
  6. Sabbir, M.G., Mowat, M.R.A. Dlc1 Isoforms Have Differential Cell Morphological Effect and Sub Cellular Localization in Murine Primary and Tumour Cells. The Canadian Cancer Research Conference , Toronto, ON, A05 pg 47 Abstract book ( Nov., 2011).
  7. Sabbir, M.G., Mowat, M.R.A. The deleted in liver cancer 1 gene (Dlc1) expression during mouse embryonic development. Mouse Genetics Meeting, Washington DC, 195C pg 43 Abstract book, June (2011).
  8. Sabbir, M.G., Preditis, H. and Mowat, M.R.A. Deleted in liver cancer 1 gene cooperates with onogenic K-ras(G12D) mutation in the induction of thymic tumours through promoter methylation. BIT’s 3rd Annual World Cancer Congress, Singapore, pg 606 Abstract book (2010).



RIOH gratefully acknowledges the generous support of



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