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School of Medicine
Phone number: (410) 502-9748
Interests: Cancer Biology, DNA Damage Biology
Titles: Professor of Radiation Oncology; Professor of Oncology, Willard and Lillian Hackerman Professor in Radiation Oncology, Director of Molecular Radiation Sciences
Schools\degrees: University of Helsinki, Finland\MD; University of Helsinki, Finland\PhD
Training: University of Massachusetts Medical Center, Worcester, MA\Postdoctoral fellowship; Sloan-Kettering Institute, New York, NY\Research associate
Research summary: The main focus of my work is to study the relevance and implications of cellular DNA damage response in cancer. In my laboratory, we strive to understand the relevance of the damage response at the cellular and organ level, and to define differences that exist between cancer and normal cells. My laboratory has made several seminal findings on the regulation of p53 tumor suppressor protein in DNA damage, and applied these to discovery screens of lead therapeutic molecules. Our goal is to dissect the mechanisms of action of these novel small-molecule lead compounds in cancer.
Sarek, G., Kurki, S., Enbäck, J., Iotzova, G., Haas, J., Laakkonen, P., Laiho, M., and Ojala, P.M. Therapeutic potential of small-molecule inhibitor of the p53-Mdm2 interaction in primary erffusion lymphomas. J. Clin. Invest. 117: 1019-1028, 2007.
Kiviharju, T., Jäämaa, S., Mönkkönen, M., Peltonen, K., Andersson, L.C., Medema, R., Peehl, D., and Laiho, M. Human prostate epithelium lacks DNA damage-induced checkpoint enforcement by inhibitory Cdk tyrosine 15 phosphorylation. Proc. Natl. Acad. Sci. USA 104: 7211-7216, 2007.
Koopal S, Furuhjelm JH, Järviluoma A, Jäämaa S, Pyakurel P, Pussinen C, Wirzenius M, Biberfeld P, Alitalo K, Laiho M, and Ojala PM. Viral oncogene-induced DNA damage response is activated in Kaposi’s sarcoma tumorigenesis. PLoS Pathogens, 3:1348-60, 2007.
Latonen, L., Jarvinen, P., and Laiho, M. Cytoskeleton-interacting LIM-domain protein CRP1 suppresses cell proliferation and protects from stress-induced cell death. Exp. Cell Res. 314: 738-47, 2008.
Band, A., Björklund, M., and Laiho, M. Phosphatidylinositol 3-kinase/Akt pathway regulates TGF-ß signaling by de-stabilizing Ski and inducing Smad7. J. Biol. Chem. 284: 35441-35449, 2009.
Björklund, M., Vaahtomeri, K., Peltonen, K., Viollet, B., Mäkelä, T., Band, A.M., and Laiho, M. Non-cdk-bound p27 (p27NCDK) is a marker for cell stress and is regulated through the Akt/PKB and AMPK-kinase pathways. Exp. Cell Res. class="src"316: 762-74, 2010.
Sarek, G., Järviluoma, A., Moore, H.M., Tojkander, S., Vartia, S., Biberfeld, P., *Laiho, M., *Ojala, P. Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency. PLoS Pathogens 6: e1000818, 2010. *equal contribution
Jäämaa, S., af Hällström, T.M., Sankila, A., Rantanen, V., Koistinen, H., Stenman, U., Zhang, Z., Yang, Z., De Marzo, A., Taari, K., Ruutu, M., Andersson, L.C., and Laiho, M. DNA damage recognition via activated ATM and p53 pathway in non-proliferating human prostate tissue. Cancer Res. 70: class="src"8630-41, 2010.
Peltonen, K., Colis, L., Liu, H., Jäämaa, S., Moore, H.M., Enbäck, J., Laakkonen, P., Vaahtokari, A., Jones, R.J., af Hällström, T.M., and Laiho, M. Identification of novel p53 pathway activating small-molecule compounds reveals unexpected similarities with known therapeutic agents. PLoS ONE 5(9): e12996, 2010.
Latonen, L., Moore, H.M., Bai, B., Jäämaa, S., and Laiho, M. Proteasome inhibitors induce nucleolar aggregation of proteasome target proteins and polyadenylated RNA by altering ubiquitin availability. Oncogene 30:790-805, 2011.
Ni, X., Zhang, Y., Ribas, J., Chowdhury, W.M., Castanares, M., Zhang, Z., Laiho, M., DeWeese, T.L., Lupold, S.E. Prostate-targeted radiosensitization via aptamer-shRNA chimeras in human tumor xenografts. J. Clin. Invest. In press, 2011.