Program Director/Principal Investigator (Last, First, Middle) : McManus, Kirk
BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
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NAME
POSITION TITLE
Kirk McManus
Associate Professor
eRA COMMONS USER NAME (credential, e.g., agency login)
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
DEGREE
(if applicable)
YEAR(s)
The University of Manitoba
BSc (Honors)
1991/9-1995/5
Genetics
The University of Manitoba
MSc
1997/5-1999/8
Human Genetics
University of Alberta
PhD
1999/9-2004/12
Experimental Oncology
Post-doctorate
2005/1-2009/5
Molecular Genetics
INSTITUTION AND LOCATION
University of British Columbia
A.
FIELD OF STUDY
Personal Statement
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 in Oncology & Hematology
(RIOH) 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 post-translational histone
modifications and their influence on chromosome segregation. His post-doctoral 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 his research interests focus
on identifying and characterizing genes that regulate chromosome stability in a cancer context and exploiting
these characteristics to identify novel therapeutic targets. He currently couples genetics, biochemistry and
cellular biology along with quantitative imaging microscopy to identify both genes and targets of interest.
B.
Positions and Honors
Positions and Employment
1997/5-1998/8
Graduate Student (MSc), Human Genetics, Faculty of Medicine, The University of Manitoba
1999/9-2004/12 Graduate Student (PhD), Oncology, Faculty of Medicine & Dentistry, University of Alberta
2005/1-2009/5
Post-Doctoral Fellow, Michael Smith Laboratories, University of British Columbia
2009/6
Senior Scientist, Manitoba Institute of Cell Biology
2009/6-2015/03 Assistant Professor, Biochemistry & Medical Genetics, Rady Faculty of Health Sciences,
The University of Manitoba
2015/03
Associate Professor, Biochemistry & Medical Genetics, Rady Faculty of Health Sciences,
The University of Manitoba
Honors
2016
2016
2014
University of Manitoba Graduate Student Association Teaching Award
Merit Award for Research, Teaching and Service, University of Manitoba
Ken Hughes Young Investigator Award for Medical Research, Faculty of Health Sciences,
College of Medicine
0925-0001/0002 (Rev. 08/12)
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Biographical Sketch Format Page
Program Director/Principal Investigator (Last, First, Middle) : McManus, Kirk
2014
2006 – 2009
Rh Award for Outstanding Contributions to Scholarship and Research in the Health
Sciences, Winnipeg Rh Foundation Inc./University of Manitoba
CIHR/Manitoba Health Research Council Regional Partnership Program – New Investigator
Salary Award
Canadian Institutes of Health Research Post-doctoral Fellowship
Memberships
2010 – Present
2009 – Present
2007 – Present
Member, Canadian Society for Molecular Biosciences
Member, Genetics Society of America
Member, American Association for Cancer Research
2010 – 2012
C.
Selected Peer-reviewed Publications
1. McManus, K.J. and Hendzel, M.J. CBP, a transcriptional coactivator and acetyltransferase. Biochem Cell
Biol. 2001;79:253-66.
2. McManus, K.J. and Hendzel, M.J. Quantitative analysis of CBP- and P300-induced histone acetylation in
vivo using native chromatin. Mol Cell Biol. 2003;23:7611-27.
3. Biron, V.L., McManus, K.J., Hu, N., Hendzel, M.J. and Underhill, D.A. Distinct dynamics and distribution of
histone methyl-lysine derivatives in mouse development. Dev Biol. 2004;15:337-51.
4. McManus, K.J. and Hendzel M.J. ATM-dependent DNA damage-independent mitotic phosphorylation of
H2AX in normally growing mammalian cells. Mol Biol Cell. 2005;16:5013-25.
5. McManus, K.J. and Hendzel, M.J. Using quantitative imaging microscopy to define the target substrate
specificities of histone post-translational-modifying enzymes. Methods. 2005;36:351-61.
6. McManus, K.J., Biron V.L., Heit, R., Underhill D.A. and Hendzel, M.J. 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. 2006;281:8888-97.
7. McManus, K.J. and Hendzel, M.J. The relationship between histone H3 phosphorylation and acetylation
throughout the mammalian cell cycle. Biochem Cell Biol. 2006;84:640-57.
8. McManus, K.J., Stephens, D.A., Adams, N.M., Islam S.A., Freemont, P.S. and Hendzel, M.J. The
transcriptional regulator CBP has defined spatial associations within interphase nuclei. PLoS Comput Biol.
2006;2:1271-83.
9. *Barber, T., *McManus, K., *Yuen, K.W.Y., Reis, M., Parmigiani, G., Shen D., Barrett, I., Nouhi, Y.,
Spencer, F., Markowitz, S., Velculescu, V., Kinzler, K.W., Vogelstein, B., Lengauer, C., and Hieter, P.
Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers. P Natl Acad
Sci USA. 2008;105:3443-8. *These authors contributed equally to this work and are listed alphabetically.
10. Houston, S.I., McManus, K.J., Adams, M.M., Sims, J.K., Carpenter, P.B., Hendzel, M.J. and Rice, J.C.
Catalytic function of the PR-Set7 histone H4 lysine 20 monomethyltransferase is essential for mitotic entry
and genomic stability. J Biol Chem. 2008;28:19478-88.
11. McManus, K.J., Barrett I.J., Nouhi, Y. and Hieter, P.A. Specific synthetic lethal killing of RAD54B deficient
human colorectal cancer cells by FEN1 silencing. P Natl Acad Sci USA. 2009;106:3276-81.
12. Ben-Aroya, S., Agmon, N., Yuen K., Kwok, T., McManus, K., Kupiec, M., and Hieter, P. Proteasome
nuclear activity affects chromosome stability by controlling the turnover of Mms22, a protein important for
DNA repair. PLoS Genetics. 2010;6:e1000852.
13. Bell DW, Sikdar N, Lee Y-Y, Price JC, Chatterjee R, Park H-D, Fox J, Ishiai M, Rudd ML, Pollock LM,
Fogoros SF, Mohamed H, Hanigan CL, NISC, Zhang S, Cruz P, Renaud G, Hansen NF, Cherukuri PF,
Borate B, McManus KJ, Stoepel J, Sipahimalani P, Godwin AK, Sgroi DC, Merino MJ, Elliot G, Elkahloun
A, Vinson C, Takata M, Mullikin JC, Wolfsberg TG, Hieter P, Lim D-S, Myung K. Predisposition to cancer
caused by genetic and functional defects of mammalian Atad5. PLoS Genetics. 2011;7:e1002245.
14. van Pel, D.M., Barrett, I.J., Shimizu, Y., Sajesh, B.V., Guppy, B.J., Pfeifer, T., McManus, K.J., and Hieter,
P. An evolutionarily conserved synthetic lethal interaction network identifies FEN1 as a broad-spectrum
target for anticancer therapeutic development. PLoS Genetics. 2013;9:e10003254.
PHS 398/2590 (Rev. 09/04)
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Program Director/Principal Investigator (Last, First, Middle) : McManus, Kirk
15. Price, J.C., Pollock, L.M., Rudd, M.L., Fogoros, S.K., Mohamed, H., Hanigan, C.L., NISC Comparative
Sequencing Program, Zhang, S., Cruz, P., Hansen, N.F., Cherukuri, P.F., McManus, K.J., Godwin, A.K.,
Sgroi, D.C., Mullikin, J.C., Wolfsberg, T.G., Merino, M.J., Hieter, P., and Bell, D.W. Sequencing of
candidate chromosome instability genes in endometrial cancers reveals somatic mutations in ESCO1,
CHTF18, and MRE11A. PLoS ONE. 2013;8:e63313.
16. Thompson, L.L., Guppy, B.J., Sawchuk, L., Davie, J.R., and McManus, K.J. Regulation of chromatin
structure via histone post-translational modification and the link to carcinogenesis. Cancer Metast Rev.
2013; 32:363-73.
17. Sajesh, B.V., Lichtensztejn, Z., and McManus, K.J. Sister chromatid defects are associated with
chromosome instability in Hodgkin lymphoma cells. BMC Cancer. 2013;13:391.
18. Sajesh, B.V., Bailey, M.L., Lichtensztejn, Z., Hieter, P., and McManus, K.J. Synthetic lethal targeting of
superoxide dismutase 1 selectively kills RAD54B-deficient cells. Genetics. 2013;195:757-67.
19. Sajesh, B.V., Guppy, B.J., and McManus, K.J. Synthetic genetic targeting of genome instability in cancer.
Cancers 2013;5:739-61.
20. Cisyk, A.L., Singh, H., and McManus, K.J. Establishing a biological profile for interval colorectal cancers.
Dig Dis Sci 2014;59:2390-402.
21. Guppy BJ, McManus KJ. Mitotic accumulation of di-methylated lysine 79 of Histone H3 is important for
maintaining genome integrity during mitosis in human cells. Genetics. 2015; 199:423-33.
22. Cisyk, A.L., Penner-Goeke, S., Lichtensztejn, Z., Nugent, Z., Wightman, R., Singh, H., and McManus, K.J.
Chromosome instability is correlated with interval colorectal cancers. Neoplasia 2015;17:306-16.
23. Thompson, L.L. and McManus, K.J. A novel multiplexed and image-based approach to identify
chromosome instability genes in human cells. PLoS ONE 2015;10:e0123200.
24. Sajesh, B.V., and McManus, K.J. Targeting SOD1 Induces Synthetic Lethal Killing in BLM- and CHEK2deficient Colorectal Cancer Cells. Oncotarget 2015;6:27907-22.
25. Yan, Y., Cooper, C., Hamedani, M.K., Guppy, B., Wayne, X., Tsuyuki, D., Zhang, C., Nugent, Z.,
Blanchard, A., Davie, J.R., McManus, K., Murphy, L.C., Myal, Y., and Leygue, E. The Steroid Receptor
RNA Activator Protein (SRAP) Controls Cancer Cell Migration/Motility. FEBS Letters 2015;589:4010-8
D.
Research Support
2016 – 2017 CancerCare Manitoba Foundation – Operating Grant
Principal Applicant: Dr. Michael Mowat
Title: Understanding and exploiting DLC1 tumor suppressor interaction with non-muscle myosin.
Co-Applicants: Dr. Kirk McManus
2016 – 2018 University of Manitoba – Collaborative Research Grant
Principal Applicant: Dr. Mark Nachtigal
Title: Investigating chromosomal instability in ovarian cancer stem cells.
Co-Applicants: Drs. Tamra Ogilvie-Werbowetski & Kirk McManus
2015 – 2017 CancerCare Manitoba Foundation – Operating Grant
Principal Applicant: Dr. Kirk McManus
Title: Examining PARP1 as a novel drug target in RAD54B-deficient colorectal cancer cells.
2013 – 2018 Canadian Foundation for Innovation – Infrastructure Operating Funds
Title: Molecular determinants of chromosome instability in cancer: Identification of therapeutic
targets.
2012 – 2017 Natural Sciences & Engineering Council of Canada – Discovery Grant
Title: Identifying the molecular determinants of chromosome stability in humans.
2011 – 2016 Canadian Institutes of Health Research – Operating Grant
Title: Characterizing and targeting diminished RNF20 expression in cancer.
PHS 398/2590 (Rev. 09/04)
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