Dr. Armin Gamper is currently appointed as Assistant Professor in the Division of Experimental Oncology in the Faculty of Medicine and Dentistry.
Students and Postdocs are welcome. For available research positions and details on research please visit the lab web page.
Studying DNA Damage Signaling to Understand Cancer Development and to Improve Cancer Therapy
Higher eukaryotes have evolved a complex DNA damage response that involves DNA repair, cell cycle control and apoptosis. Aberration in each of these cellular processes can contribute to cancer development. At the same time fast proliferating cells such as cancer cells are particularly vulnerable to unrepaired DNA damage. This provides the basis for radiotherapy and most chemotherapies. Elucidating the mechanisms governing DNA repair and the DNA damage response therefore can help both cancer prevention and therapy. My graduate and postdoctoral studies have focused on examining the signalling pathways from DNA damage sensing to the activation of stress-response genes. The focus of my lab, established in 2015 at the University of Alberta, is to study the activation of the sensors of DNA double strand breaks, particularly in the context of chromatin, and the interplay between factors determining cell plasticity and the DNA Damage Response. Current research interests in the lab include in vitro and in vivo studies of: 1) the DNA damage signalling mechanisms and the therapeutic potential of targeting them; 2) the regulation of stemness transcription factors by DNA damage and hypoxia; 3) ionizing radiation-induced breast cancer cell plasticity; 4) breast cancer and lymphoma mouse models for image-guided radiation therapy; 5) development of novel methods to identify and visualize proteins at DNA-damage sites; 6) establishment of in vitro biological models to improve brachytherapy, 7) development of non-invasive tools to assess tumour response to ionizing radiation. My long-term goal is to find proteins that are drug targets for cancer treatment (such as radiosensitizers for radiation therapy) or prognostic markers that increase the predictive value of therapeutic outcome (such as genes whose loss or overexpression synergistically enhances tumour progression).
My cancer and radiation biology lab combines the expertise in various disciplines to enable the knowledge transfer from molecular findings to preclinical studies in animals and ultimately to the clinic. My projects are founded on the multidisciplinary expertise I have developed during my training years, having used techniques and published in fields spanning from medicinal chemistry, biochemistry (including proteomics), molecular biology, radiation biology and oncology. Furthermore, I have assembled a team that expands the repertoire to animal studies and radiation treatment planning.
Cancer Biology, DNA damage response, biomarkers, signal transduction, kinase inhibitors
1. Bukhari A.B., Lewis C.W., Pearce J.J., Luong D., Chan G.K., Gamper A.M. Inhibiting Wee1 and ATR kinases produces tumor-selective synthetic lethality and suppresses metastasis. J. Clin. Invest. 129(3):1329-1344, 2019
2. Moiseeva T., Gamper A.M., Hood B., Conrads T., Bakkenist C.J. Human DNA polymerase epsilon is phosphorylated at serine-1940 after DNA damage and interacts with the iron-sulfur complex chaperones CIAO1 and MMS19. DNA Repair 43: 9-17, 2016
3. Hu D., Gur M., Zhou Z., Gamper A., Hung M.C., Fujita N., Lan L., Bahar I., Wan Y. Interplay between arginine methylation and ubiquitylation regulates KLF4-mediated genome stability and carcinogenesis. Nat. Commun. 6: 8419, 2015
4. Kwun H.J., Shuda M., Camacho C., Gamper A., Thant M., Chang Y., and Moore P.S. Restricted Protein Phosphatase 2A Targeting by Merkel Cell Polyomavirus Small T Antigen. J. Virol. 89(8):4191-200, 2015.
5. Gamper A.M., Rofougaran R., Watkins S.C., Greenberger J.S., Beumer J.H., Bakkenist C.J. ATR kinase activation in G1 phase facilitates the repair of ionizing radiation-induced DNA damage. Nucleic Acids Res.41:10334-44, 2013.
6. Gamper A.M., Choi S., Matsumoto Y., Banerjee D., Tomkinson A.E., Bakkenist C.J. ATM physically and functionally interacts with PCNA to regulate DNA synthesis. J. Biol. Chem. 287: 12445-12454, 2012.
7. Gamper A.M., Qiao X., Kim J., Zhang L., DeSimone M.C., Rathmell W.K., Wan Y. Regulation of KLF4 turnover reveals an unexpected tissue specific role of pVHL in tumorigenesis. Mol. Cell45: 233-243, 2012.
8. Choi S., Gamper A.M., White J.S., Bakkenist C.J. Inhibition of ATM kinase activity does not phenocopy ATM protein disruption: implications for the clinical utility of ATM kinase inhibitors. Cell Cycle 9: 4052-4057, 2010.
9. Qiao X., Zhang L., Gamper A.M., Fujita T. Wan Y. APC/C-Cdh1: From cell cycle to cellular differentiation and genomic integrity. Cell Cycle 9: 3904 - 3912, 2010. (Review)
10. Gamper A.M., Kim J., & Roeder R.G. The STAGA subunit hADA2b is an important regulator of hGCN5 catalysis. Mol. Cell. Biol. 1: 266-80, 2009.
11. Gamper A.M., Roeder R.G. Multivalent Binding of p53 to the STAGA Complex mediates Coactivator Recruitment after UV Damage. Mol. Cell. Biol. 8: 2517-27, 2008.
12. Palhan V., Chen S., Peng G.H., Tjernberg A., Gamper A.M., Chait B.T., La Spada A.R., Roeder R.G. Polyglutamine-expanded ataxin-7 inhibits STAGA histone acetyltransferase activity to produce retinal degeneration. Proc. Natl. Sci. Acad. USA. 102: 8472-7, 2005.
13. Martinez E., Palhan V., Tjernberg A., Lymar E.S., Gamper A.M., Kundu T.K., Chait B.T., Roeder R.G. Human STAGA Complex is a Chromatin-Acetylating Transcription Coactivator that Interacts with Pre-mRNA Splicing and DNA Damage-Binding Factors In Vivo. Mol. Cell. Biol. 21: 6782-95, 2001.