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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

Epigenetics (2000-2006)
 
McManus, K.J., V.L. Biron, R. Heit, D.A. Underhill, and M.J. Hendzel. 2006. Dynamic Changes in Histone H3 Lysine 9 Methylations: IDENTIFICATION OF A MITOSIS-SPECIFIC FUNCTION FOR DYNAMIC METHYLATION IN CHROMOSOME CONGRESSION AND SEGREGATION. J Biol Chem. 281:8888-97.
 
McManus, K.J., and M.J. Hendzel. 2005a. ATM-dependent DNA damage-independent mitotic phosphorylation of H2AX in normally growing mammalian cells. Mol Biol Cell. 16:5013-25.
 
McManus, K.J., and M.J. Hendzel. 2005b. Using quantitative imaging microscopy to define the target substrate specificities of histone post-translational-modifying enzymes. Methods. 36:351-61.
 
Keats, J.J., C.A. Maxwell, B.J. Taylor, M.J. Hendzel, M. Chesi, P.L. Bergsagel, L.M. Larratt, M.J. Mant, T. Reiman, A.R. Belch, and L.M. Pilarski. 2005. Overexpression of transcripts originating from the MMSET locus characterizes all t(4;14)(p16;q32)-positive multiple myeloma patients. Blood. 105:4060-9.
 
Biron, V.L., K.J. McManus, N. Hu, M.J. Hendzel, and D.A. Underhill. 2004. Distinct dynamics and distribution of histone methyl-lysine derivatives in mouse development. Dev Biol. 276:337-51.
 
McManus, K.J., and M.J. Hendzel. 2003. Quantitative analysis of CBP- and P300-induced histone acetylations in vivo using native chromatin. Mol Cell Biol. 23:7611-27.
 
Fischle, W., F. Dequiedt, M.J. Hendzel, M.G. Guenther, M.A. Lazar, W. Voelter, and E. Verdin. 2002. Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR. Mol Cell. 9:45-57.
 
Boisvert, F.M., M.J. Kruhlak, A.K. Box, M.J. Hendzel, and D.P. Bazett-Jones. 2001. The transcription coactivator CBP is a dynamic component of the promyelocytic leukemia nuclear body. J Cell Biol. 152:1099-106.
 
Fischle, W., F. Dequiedt, M. Fillion, M.J. Hendzel, W. Voelter, and E. Verdin. 2001. Human HDAC7 histone deacetylase activity is associated with HDAC3 in vivo. J Biol Chem. 276:35826-35.
 
Kruhlak, M.J., M.J. Hendzel, W. Fischle, N.R. Bertos, S. Hameed, X.J. Yang, E. Verdin, and D.P. Bazett-Jones. 2001. Regulation of global acetylation in mitosis through loss of histone acetyltransferases and deacetylases from chromatin. J Biol Chem. 276:38307-19.
 
McManus, K.J., and M.J. Hendzel. 2001. CBP, a transcriptional coactivator and acetyltransferase. Biochem Cell Biol. 79:253-66.
 
Histone H1 (2000-2006)
 
Th'ng, J.P., R. Sung, M. Ye, and M.J. Hendzel. 2005. H1 family histones in the nucleus. Control of binding and localization by the C-terminal domain. J Biol Chem. 280:27809-14.
 
Hendzel, M.J., M.A. Lever, E. Crawford, and J.P. Th'ng. 2004. The C-terminal domain is the primary determinant of histone H1 binding to chromatin in vivo. J Biol Chem. 279:20028-34.
 
Lever, M.A., J.P. Th'ng, X. Sun, and M.J. Hendzel. 2000. Rapid exchange of histone H1.1 on chromatin in living human cells. Nature. 408:873-6.
 
Nuclear Structure, Function, and Dynamics (2000-2006)
 
McDonald, D., G. Carrero, C. Andrin, G. de Vries, and M.J. Hendzel. 2006. Nucleoplasmic beta-actin exists in a dynamic equilibrium between low-mobility polymeric species and rapidly diffusing populations. J Cell Biol. 172:541-52.
 
Carrero, G., M.J. Hendzel, and G. de Vries. 2006. Modelling the compartmentalization of splicing factors. J Theor Biol. 239:298-312.
 
Andrin, C., and M.J. Hendzel. 2004. F-actin-dependent insolubility of chromatin-modifying components. J Biol Chem. 279:25017-23.
 
Carrero, G., E. Crawford, M.J. Hendzel, and G. de Vries. 2004a. Characterizing fluorescence recovery curves for nuclear proteins undergoing binding events. Bull Math Biol. 66:1515-45.
 
Carrero, G., E. Crawford, J. Th'ng, G. de Vries, and M.J. Hendzel. 2004b. Quantification of protein-protein and protein-DNA interactions in vivo, using fluorescence recovery after photobleaching. Methods Enzymol. 375:415-42.
 
Carrero, G., D. McDonald, E. Crawford, G. de Vries, and M.J. Hendzel. 2003. Using FRAP and mathematical modeling to determine the in vivo kinetics of nuclear proteins. Methods. 29:14-28.
 
Hendzel, M.J., M.J. Kruhlak, N.A. MacLean, F. Boisvert, M.A. Lever, and D.P. Bazett-Jones. 2001. Compartmentalization of regulatory proteins in the cell nucleus. J Steroid Biochem Mol Biol. 76:9-21.
 
Kruhlak, M.J., M.A. Lever, W. Fischle, E. Verdin, D.P. Bazett-Jones, and M.J. Hendzel. 2000. Reduced mobility of the alternate splicing factor (ASF) through the nucleoplasm and steady state speckle compartments. J Cell Biol. 150:41-51.
 
Maxwell, C.A., and M.J. Hendzel. 2001. The integration of tissue structure and nuclear function. Biochem Cell Biol. 79:267-74.
 
Boisvert, F.M., M.J. Kruhlak, A.K. Box, M.J. Hendzel, and D.P. Bazett-Jones. 2001. The transcription coactivator CBP is a dynamic component of the promyelocytic leukemia nuclear body. J Cell Biol. 152:1099-106.
 
Boisvert, F.M., M.J. Hendzel, and D.P. Bazett-Jones. 2000. Promyelocytic leukemia (PML) nuclear bodies are protein structures that do not accumulate RNA. J Cell Biol. 148:283-92.
 
DNA Damage and DNA Repair (2000-2006)
 
Boisvert, F.M., M.J. Hendzel, J.Y. Masson, and S. Richard. 2005. Methylation of MRE11 regulates its nuclear compartmentalization. Cell Cycle. 4:981-9.
 
Gagne, J.P., M.E. Bonicalzi, P. Gagne, M.E. Ouellet, M.J. Hendzel, and G.G. Poirier. 2005. Poly(ADP-ribose) glycohydrolase is a component of the FMRP-associated messenger ribonucleoparticles. Biochem J. 392:499-509.
 
Gagne, J.P., M.J. Hendzel, A. Droit, and G.G. Poirier. 2006. The expanding role of poly(ADP-ribose) metabolism: current challenges and new perspectives. Curr Opin Cell Biol. 18:145-51.
 
Haince, J.F., M.E. Ouellet, D. McDonald, M.J. Hendzel, and G.G. Poirier. 2006. Dynamic relocation of poly(ADP-ribose) glycohydrolase isoforms during radiation-induced DNA damage. Biochim Biophys Acta. 1763:226-37.
 
Haince, J.F., M. Rouleau, M.J. Hendzel, J.Y. Masson, and G.G. Poirier. 2005. Targeting poly(ADP-ribosyl)ation: a promising approach in cancer therapy. Trends Mol Med. 11:456-63.
Han, J., M.J. Hendzel, and J. Allalunis-Turner. 2006.
 
Quantitative analysis reveals asynchronous and more than DSB-associated histone H2AX phosphorylation after exposure to ionizing radiation. Radiat Res. 165:283-92.
 
Rodrigue, A., M. Lafrance, M.C. Gauthier, D. McDonald, M. Hendzel, S.C. West, M. Jasin, and J.Y. Masson. 2006. Interplay between human DNA repair proteins at a unique double-strand break in vivo. Embo J. 25:222-31.