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Experimental Oncology

Michael Hendzel

Professor
Experimental Oncology
Department of Oncology
University of Alberta
Cross Cancer Institute
11560 University Avenue
Edmonton, Alberta T6G 1Z2
Tel: 780.432.8439
michael.hendzel@albertahealthservices.ca

Profile

MJ Hendzel Laboratory

Approximately 40% of Canadians are expected to have cancer at some point in their lives and approximately 25% of Canadians are expected to die of cancer.  It is only recently that modern biology has begun to impact upon the clinical treatment of cancer patients.  Despite early successes in so-called rationally designed therapy, much of the fundamental biology that provides the foundation for rationally designed therapy remains to be discovered and characterized.  My research laboratory investigates the basic biology of the genome and the cell nucleus, which houses the genome.  The maintenance of genome stability (mechanisms that ensure the faithful transmission of chromosome number of sequence content), the regulation of DNA double strand break repair, and the regulation of the genome through epigenetic mechanisms are being studied at the level of single cells with the objective of identifying mechanisms that have the potential to be translated into novel rationale therapies.  We are currently funded by the Canadian Institutes of Health Research, the National Cancer Institute of Canada, and the Alberta Cancer Board to study how the cell nucleus and chromatin function in normal and transformed (cancer) cells. 
 

 

Publications

Conn, K.L., M.J. Hendzel, and L.M. Schang, Linker histones are mobilized during infection with herpes simplex virus type 1. Journal of Virology, 2008. 82(17): p. 8629-8646.
 
Corry, G.N., M.J. Hendzel, and D.A. Underhill, Subnuclear localization and mobility are key indicators of PAX3 dysfunction in Waardenburg syndrome. Human Molecular Genetics, 2008. 17(12): p. 1825-1837.
 
Gagne, J.P., M. Isabelle, K.S. Lo, S. Bourassa, M.J. Hendzel, V.L. Dawson, T.M. Dawson, and G.G. Poirier, Proteome-wide identification of poly(ADP-ribose) binding proteins and poly(ADP-ribose)-associated protein complexes. Nucleic Acids Research, 2008. 36(22): p. 6959-6976.
 
Gieni, R.S., G.K.T. Chan, and M.J. Hendzel, Epigenetics regulate centromere formation and kinetochore function. Journal of Cellular Biochemistry, 2008. 104(6): p. 2027-2039.
 
Gieni, R.S. and M.J. Hendzel, Mechanotransduction from the ECM to the genome: Are the pieces now in place? Journal of Cellular Biochemistry, 2008. 104(6): p. 1964-1987.
 
Haince, J.F., D. McDonald, A. Rodrigue, U. Dery, J.Y. Masson, M.J. Hendzel, and G.G. Poirier, PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites. Journal of Biological Chemistry, 2008. 283(2): p. 1197-1208.
 
Houston, S.I., K.J. McManus, M.M. Adams, J.K. Sims, P.B. Carpenter, M.J. Hendzel, and J.C. Rice, Catalytic function of the PR-Set7 histone H4 lysine 20 monomethyltransferase is essential for mitotic entry and genomic stability. Journal of Biological Chemistry, 2008. 283(28): p. 19478-19488.
 
Ismail, I.H. and M.J. Hendzel, The gamma-H2A.X: Is it just a surrogate marker of double-strand breaks or much more? Environmental and Molecular Mutagenesis, 2008. 49(1): p. 73-82.
 
Shen, Q., J.J. Rahn, J. Zhang, N. Gunasekera, X.J. Sun, A.R.E. Shaw, M.J. Hendzel, P. Hoffman, A. Bernier, and J.C. Hugh, MUC1 initiates Src-CrkL-Rac1/Cdc42-mediated actin cytoskeletal protrusive motility after ligating intercellular adhesion molecule-1. Molecular Cancer Research, 2008. 6(4): p. 555-567.
 
Carrero, G., N. Raghuram, J. Th'ng, and M. Hendzel, A Method for Assessing Kinetic Changes of Histone H1 after Post-Translational Modifications, in Numerical Analysis and Applied Mathematics, Vols 1 and 2, T.E. Simos, G. Psihoyios, and C. Tsitouras, Editors. 2009, Amer Inst Physics: Melville. p. 1306-1309.
 
Dryhurst, D., T. Ishibashi, K.L. Rose, J.M. Eirin-Lopez, D. McDonald, B. Silva-Moreno, N. Veldhoen, C.C. Helbing, M.J. Hendzel, J. Shabanowitz, D.F. Hunt, and J. Ausio, Characterization of the histone H2A.Z-1 and H2A.Z-2 isoforms in vertebrates. Bmc Biology, 2009. 7: p. 16.
 
Gagne, J.P., X. Moreel, P. Gagne, Y. Labelle, A. Droit, M. Chevalier-Pare, S. Bourassa, D. McDonald, M.J. Hendzel, C. Prigent, and G.G. Poirier, Proteomic Investigation of Phosphorylation Sites in Poly(ADP-ribose) Polymerase-1 and Poly(ADP-ribose) Glycohydrolase. Journal of Proteome Research, 2009. 8(2): p. 1014-1029.
 
Gieni, R.S. and M.J. Hendzel, Polycomb group protein gene silencing, noncoding RNA, stem cells, and cancer. Biochemistry and Cell Biology-Biochimie Et Biologie Cellulaire, 2009. 87(5): p. 711-746.
 
Gieni, R.S. and M.J. Hendzel, Actin dynamics and functions in the interphase nucleus: moving toward an understanding of nuclear polymeric actin. Biochemistry and Cell Biology-Biochimie Et Biologie Cellulaire, 2009. 87(1): p. 283-306.
 
Han, J.X., I. Ma, M.J. Hendzel, and J. Allalunis-Turner, The cytotoxicity of gamma-secretase inhibitor I to breast cancer cells is mediated by proteasome inhibition, not by gamma-secretase inhibition. Breast Cancer Research, 2009. 11(4): p. 12.
 
Heit, R., J.B. Rattner, G.K.T. Chan, and M.J. Hendzel, G2 histone methylation is required for the proper segregation of chromosomes. Journal of Cell Science, 2009. 122(16): p. 2957-2968.
 
Raghuram, N., G. Carrero, J. Th'ng, and M.J. Hendzel, Molecular dynamics of histone H1. Biochemistry and Cell Biology-Biochimie Et Biologie Cellulaire, 2009. 87(1): p. 189-206.
 
Corry, G.N., N. Raghuram, K.K. Missiaen, N.H. Hu, M.J. Hendzel, and D.A. Underhill, The PAX3 Paired Domain and Homeodomain Function as a Single Binding Module In Vivo to Regulate Subnuclear Localization and Mobility by a Mechanism That Requires Base-Specific Recognition. Journal of Molecular Biology, 2010. 402(1): p. 178-193.
 
Isabelle, M., X. Moreel, J.P. Gagne, M. Rouleau, C. Ethier, P. Gagne, M.J. Hendzel, and G.G. Poirier, Investigation of PARP-1, PARP-2, and PARG interactomes by affinity-purification mass spectrometry. Proteome Science, 2010. 8: p. 11.
 
Ishibashi, T., A. Li, J.M. Eirin-Lopez, M. Zhao, K. Missiaen, D.W. Abbott, M. Meistrich, M.J. Hendzel, and J. Ausio, H2A.Bbd: an X-chromosome-encoded histone involved in mammalian spermiogenesis. Nucleic Acids Research, 2010. 38(6): p. 1780-1789.
 
Ismail, I.H., C. Andrin, D. McDonald, and M.J. Hendzel, BMI1-mediated histone ubiquitylation promotes DNA double-strand break repair. Journal of Cell Biology, 2010. 191(1): p. 45-60.
 
Raghuram, N., G. Carrero, T.J. Stasevich, J.G. McNally, J. Th'ng, and M.J. Hendzel, Core Histone Hyperacetylation Impacts Cooperative Behavior and High-Affinity Binding of Histone H1 to Chromatin. Biochemistry, 2010. 49(21): p. 4420-4431.
 
Rouleau, M., A. Patel, M.J. Hendzel, S.H. Kaufmann, and G.G. Poirier, PARP inhibition: PARP1 and beyond. Nature Reviews Cancer, 2010. 10(4): p. 293-301.
 
Carrero, G., C. Conteras, and M.J. Hendzel, Visualizing the distribution of proteins and estimating their kinetic parameters using Virtual Photoactivated Fluorescence (VPAF). GSTF Digital Library Journal of Biology, 2011. 1(1): p. Paper 4.
 
Conn, K.L., M.J. Hendzel, and L.M. Schang, Core Histones H2B and H4 Are Mobilized during Infection with Herpes Simplex Virus 1. Journal of Virology, 2011. 85(24): p. 13234-13252.
 
Furdas, S.D., S. Shekfeh, E.M. Bissinger, J.M. Wagner, S. Schlimme, V. Valkov, M. Hendzel, M. Jung, and W. Sippl, Synthesis and biological testing of novel pyridoisothiazolones as histone acetyltransferase inhibitors. Bioorganic & Medicinal Chemistry, 2011. 19(12): p. 3678-3689.
 
Gieni, R.S., I.H. Ismail, S. Campbell, and M.J. Hendzel, Polycomb group proteins in the DNA damage response A link between radiation resistance and "stemness". Cell Cycle, 2011. 10(6): p. 883-894.
 
Han, J.X., J. Allalunis-Turner, and M.J. Hendzel, Characterization and comparison of protein complexes initiated by the intracellular domain of individual Notch paralogs. Biochemical and Biophysical Research Communications, 2011. 407(3): p. 479-485.
 
Han, J.X., M.J. Hendzel, and J. Allalunis-Turner, Notch signaling as a therapeutic target for breast cancer treatment? Breast Cancer Research, 2011. 13(3): p. 8.
 
Hsu, C.Y.M., M. Hendzel, and H. Uludag, Improved transfection efficiency of an aliphatic lipid substituted 2 kDa polyethylenimine is attributed to enhanced nuclear association and uptake in rat bone marrow stromal cell. Journal of Gene Medicine, 2011. 13(1): p. 46-59.
 
Lachapelle, S., J.P. Gagne, C. Garand, M. Desbiens, Y. Coulombe, V.A. Bohr, M.J. Hendzel, J.Y. Masson, G.G. Poirier, and M. Lebel, Proteome-wide Identification of WRN-Interacting Proteins in Untreated and Nuclease-Treated Samples. Journal of Proteome Research, 2011. 10(3): p. 1216-1227.
 
Rouleau, M., V. Saxena, A. Rodrigue, E.R. Paquet, A. Gagnon, M.J. Hendzel, J.Y. Masson, M. Ekker, and G.G. Poirier, A Key Role for Poly(ADP-Ribose) Polymerase 3 in Ectodermal Specification and Neural Crest Development. Plos One, 2011. 6(1): p. 12.
 
Spencer, V.A., S. Costes, J.L. Inman, R. Xu, J. Chen, M.J. Hendzel, and M.J. Bissell, Depletion of nuclear actin is a key mediator of quiescence in epithelial cells. Journal of Cell Science, 2011. 124(1): p. 123-132.
 
Underhill, A. and M.J. Hendzel, Conference Scene: epigenetics eh! The first formal meeting of the Canadian epigenetics community. Epigenomics, 2011. 3(4): p. 409-15.
 
Zolner, A.E., I. Abdou, R.Q. Ye, R.S. Mani, M. Fanta, Y.P. Yu, P. Douglas, N. Tahbaz, S.J. Fang, T. Dobbs, C. Wang, N. Morrice, M.J. Hendzel, M. Weinfeld, and S.P. Lees-Miller, Phosphorylation of polynucleotide kinase/phosphatase by DNA-dependent protein kinase and ataxia-telangiectasia mutated regulates its association with sites of DNA damage. Nucleic Acids Research, 2011. 39(21): p. 9224-9237.
 
Andrin, C., D. McDonald, K.M. Attwood, A. Rodrigue, S. Ghosh, R. Mirzayans, J.Y. Masson, G. Dellaire, and M.J. Hendzel, A requirement for polymerized actin in DNA double-strand break repair. Nucleus, 2012. 3(4): p. 384-95.
 
Biron, V.L., A. Mohamed, M.J. Hendzel, D. Alan Underhill, and H. Seikaly, Epigenetic differences between human papillomavirus-positive and -negative oropharyngeal squamous cell carcinomas. J Otolaryngol Head Neck Surg, 2012. 41 Suppl 1: p. S65-70.
 
Ismail, I.H., J.P. Gagné, M.C. Caron, D. McDonald, Z. Xu, J.Y. Masson, G.G. Poirier, and M.J. Hendzel, CBX4-mediated SUMO modification regulates BMI1 recruitment at sites of DNA damage. Nucleic Acids Res, 2012. 40(12): p. 5497-510.
 
Krietsch, J., M.C. Caron, J.P. Gagné, C. Ethier, J. Vignard, M. Vincent, M. Rouleau, M.J. Hendzel, G.G. Poirier, and J.Y. Masson, PARP activation regulates the RNA-binding protein NONO in the DNA damage response to DNA double-strand breaks. Nucleic Acids Res, 2012. 40(20): p. 10287-301.
 
Mallette, F.A., F. Mattiroli, G. Cui, L.C. Young, M.J. Hendzel, G. Mer, T.K. Sixma, and S. Richard, RNF8- and RNF168-dependent degradation of KDM4A/JMJD2A triggers 53BP1 recruitment to DNA damage sites. EMBO J, 2012. 31(8): p. 1865-78.
 
Thambirajah, A.A., M.K. Ng, L.J. Frehlick, A. Li, J.J. Serpa, E.V. Petrotchenko, B. Silva-Moreno, K.K. Missiaen, C.H. Borchers, J. Adam Hall, R. Mackie, F. Lutz, B.E. Gowen, M. Hendzel, P.T. Georgel, and J. Ausió, MeCP2 binds to nucleosome free (linker DNA) regions and to H3K9/H3K27 methylated nucleosomes in the brain. Nucleic Acids Res, 2012. 40(7): p. 2884-97.
 
Campbell, S., I.H. Ismail, L.C. Young, G.G. Poirier, and M.J. Hendzel, Polycomb repressive complex 2 contributes to DNA double-strand break repair. Cell Cycle, 2013. 12(16): p. 2675-83.
 
Hendzel, M. and R. Greenberg, Conversations between Chromatin Modifications and DNA Double Strand Break Repair:  A Commentary. Mutat Res, 2013. 750(1-2): p. 1-4.
 
Ismail, I.H., D. McDonald, H. Strickfaden, Z. Xu, and M.J. Hendzel, A small molecule inhibitor of Polycomb repressive complex 1 inhibits ubiquitin signaling at DNA double-strand breaks. J Biol Chem, 2013. 288(37): p. 26944-54.
 
Raghuram, N., H. Strickfaden, D. McDonald, K. Williams, H. Fang, C.A. Mizzen, J.J. Hayes, J. Th'ng, and M.J. Hendzel, Pin1 promotes histone H1 dephosphorylation and stabilizes its binding to chromatin. Journal of Cell Biology, 2013. 203(1): p. 57-71.
 
Young, L.C., D.C. McDonald, and M.J. Hendzel, Kdm4b histone demethylase is a DNA damage response protein and confers a survival advantage following gamma-irradiation. J Biol Chem, 2013. 288(29): p. 21376-88.
 
Conn, K.L., M.J. Hendzel, and L.M. Schang, The Differential Mobilization of Histones H3.1 and H3.3 by Herpes Simplex Virus 1 Relates Histone Dynamics to the Assembly of Viral Chromatin. PLoS Pathog, 2013. 9(10):e1003695. Epub 2013 Oct 10.
 
Young L.C, M.J. Hendzel. The oncogenic potential of Jumonji D2 (JMJD2/KDM4) histone demethylase overexpression.  Biochem Cell Biol. 2013. 91(6): p. 369-77.
 
Stuss DP, M. Cheema, M.K. Ng, A. Martinez de Paz, B. Williamson, K. Missiaen, J.D. Cosman, D. McPhee, M. Esteller, M.J. Hendzel, K. Delaney, J. Ausió.  Impaired in vivo binding of MeCP2 to chromatin in the absence of its DNA methyl-binding domain. Nucleic Acids Res. 2013. 41(9): p. 4888-900