Dr. Laiho’s research 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 Dr. Laiho’s 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.
Dr. Laiho’s lab seeks to understand the regulatory events that prevail in cancer cells, and detect and exploit cancer cell characteristics that could be used as basis of new cancer therapies.
The approaches used in the laboratory are aimed to provide novel information on the regulation of cellular DNA damage and tumorigenesis pathways, to identify new targets for therapy, and to apply this knowledge to therapy efforts. The studies aim at a rapid transfer of findings arising from focused mechanistic studies into translational cancer research.
Lab Website: Marikki Laiho Lab
SKCCC Experimental Irradiator
Learn more about clinical trials at the Johns Hopkins Kimmel Cancer Center.
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Kurki S, Peltonen K, Latonen L, Kiviharju T, Ojala PM, Meek D, Laiho M. Nucleolar protein NPM interacts with HDM2 and protects tumor suppressor protein p53 from HDM2-mediated degradation. Cancer Cell 5(5):465-475, 2004.
Kiviharju T, Jaamaa S, Monkkonen M, Peltonen K, Andersson LC, Medema R, Peehl D, Laiho M. Human prostate epithelium lacks DNA damage-induced checkpoint enforcement by inhibitory Cdk tyrosine 15 phosphorylation. Proceedings of the National Acadademy of Sciences USA 104(17):7211-7216, 2007.
Moore HM, Bai B, Boisvert FM, Latonen L, Rantanen V, Simpson JC, Pepperkok R, Lamond AI, Laiho M. Quantitative proteomics and dynamic imaging of the nucleolus reveals distinct responses to UV and ionizing radiation. Mol. Cell. Proteomics 10(10):M111.009241-15, 2011.
Peltonen K, Colis L, Liu H, Trivedi R, Moubarek MS, Moore HM, Bai B, Rudek MA, Bieberich CJ, Laiho, M. A targeting modality for destruction of RNA polymerase I that possesses anticancer activity. Cancer Cell 25(1):77-90, 2014.
Peltonen K, Colis L, Liu H, Jaamaa S, Zhang Z, af Hallstrom T, Moore HM, Sirajuddin P, Laiho M. Small molecule BMH-compounds that inhibit RNA polymerase I and cause nucleolar stress. Mol. Cancer Ther. 13(11): 2537-2546, 2014.