Dr. Marikki Laiho
Willard and Lillian Hackerman Professor of Radiation Oncology
Professor of Radiation Oncology and Molecular Radiation Sciences
Professor of Oncology
Director, Division of Molecular Radiation Sciences
M.D., University of Helsinki Ph.D., University of Helsinki
1983 Bachelor of Medicine, University of Helsinki, Helsinki, Finland
1986 Junior house officer, Clinics of Internal Medicine, Surgery and Children’s Hospital, Helsinki University Central Hospital, Helsinki
1987 Licentiate of Medicine (M.D.), University of Helsinki
1987 Internship, Helsinki Municipal Health Services, Helsinki
1988 Doctor of Medical Science (Ph.D.), University of Helsinki, accepted with distinction
1988-89 Postdoctoral fellow, Department of Biochemistry, University of Massachusetts Medical Center, Worcester, MA
1989-90 Research Associate, Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY
1991 Docent (Senior Lecturer/Reader), Cell Biology, University of Helsinki
2009 Leadership Development Program, Johns Hopkins Medicine, Johns Hopkins University
Laboratory web site: http://mrs.radonc.jhmi.edu/html/labs/laiho_lab/
The group of Dr. Laiho focuses on the relevance and implications of cellular DNA damage responses in cancer. The sensing, detection and repair of DNA lesions are of vital importance to maintain the genomic integrity and act as barriers against the development of cancer. In advanced cancer, many pathways that govern proper DNA damage control are lost, and conditions prevail which augment the accrual of genetic errors. Several modes of cancer therapies, like radiation and many cytotoxic drugs, exploit the vulnerability of tumor cells incapable of normal damage control. The particular interest of the lab is the function and regulation of a key DNA damage response protein, the p53 tumor suppressor. The lab focuses on mechanisms mediating the activation of the p53 in response to cell stress, and on attempts to revoke its activity. The Laiho group has presented findings of altered p53 and DNA damage checkpoint responses in the prostate, which may indicate that the relaxed damage control could predispose the organ to the highly frequent tumorigenic processes observed clinically.
The approaches used in the laboratory are aimed to provide highly significant novel information on the regulation of cellular DNA damage and tumorigenesis pathways, to identify novel targets for therapy, and to provide novel lead compounds for preclinical trials. The studies aim at a rapid transfer of findings arising from focused mechanistic studies into translational cancer research.
Bjorklund, M.A.; Vaahtomeri, K.; Peltonen, K.; Viollet, B.; Makela, T.P.; Band, A.M.; Laiho, M. Non-CDK-bound p27 (p27(NCDK)) is a marker for cell stress and is regulated through the Akt/PKB and AMPK-kinase pathways. Exp Cell Res. 2010 Mar 10;316(5):762-774.
DeWeese, T.L.; Laiho, M. Molecular Determinants of Radiation. New York: Springer; 2010.
Jaamaa, S.; Af Hallstrom, T.M.; Sankila, A.; Rantanen, V.; Koistinen, H.; Stenman, U.H.; Zhang, Z.; Yang, Z.; De Marzo, A.M.; Taari, K.; Ruutu, M.; Andersson, L.C.; Laiho, M. DNA damage recognition via activated ATM and p53 pathway in nonproliferating human prostate tissue. Cancer Res. 2010 Nov 1;70(21):8630-8641.
Latonen, L.; Jarvinen, P.M.; Suomela, S.; Moore, H.M.; Saarialho-Kere, U.; Laiho, M. Ultraviolet B radiation regulates cysteine-rich protein 1 in human keratinocytes. Photodermatol Photoimmunol Photomed. 2010 Apr;26(2):70-77.
Peltonen, K.; Colis, L.; Liu, H.; Jaamaa, S.; Moore, H.M.; Enback, J.; Laakkonen, P.; Vaahtokari, A.; Jones, R.J.; af Hallstrom, T.M.; Laiho, M. Identification of novel p53 pathway activating small-molecule compounds reveals unexpected similarities with known therapeutic agents. PLoS One. 2010;5(9):e12996 Not supported through NIH funding.
Sarek, G.; Jarviluoma, A.; Moore, H.M.; Tojkander, S.; Vartia, S.; Biberfeld, P.; Laiho, M.; Ojala, P.M. Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency. PLoS Pathog. 2010 Mar;6(3):e1000818.
Sulg, M.; Kirjavainen, A.; Pajusola, K.; Bueler, H.; Ylikoski, J.; Laiho, M.; Pirvola, U. Differential sensitivity of the inner ear sensory cell populations to forced cell cycle re-entry and p53 induction. J Neurochem. 2010 Mar;112(6):1513-1526.
Latonen, L.; Moore, H.M.; Bai, B.; Jaamaa, S.; Laiho, M. Proteasome inhibitors induce nucleolar aggregation of proteasome target proteins and polyadenylated RNA by altering ubiquitin availability. Oncogene. 2010 Oct 18.