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Cancer and Chemical Biology Group

The Cancer and Chemical Biology group 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 tumourigenic processes observed clinically. DNA damage and cell stress cause activation of several stress sensing pathways, changes in chromatin organization due to engagement of the repair machineries, and in many cases, stalling of the transcriptional holocomplexes. The bulk of transcriptional activity can be attributed to the synthesis of rDNA within the nucleolus. Considering that the nucleolus is the main location of several proteins involved in DNA damage response and repair, it is a particularly interesting organelle to study for its global response to DNA damage and transcriptional stress. These studies are being conducted through quantitative image analysis applications and quantitative proteomics. We aim to define pathways relevant for the nucleolar damage response and attribute their relevance to the cellular DNA damage responses.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.

Publications

Marikki Laiho received her MD and PhD in Medical Science in 1988 (University of Helsinki, Finland). She obtained international research experience as a post-doctoral fellow at the University of Massachusettes Medical Center in Worcester, Massachusettes, USA (1988-89). She also served as Research Associate at the Memorial Sloan-Kettering Cancer Center in New York, NY, USA (1989-90). Most recently, she has served as the Williard and Lillian Hackerman Professor of Radiation Oncology and Director of the Division of Molecular Radiation Sciences at the Johns Hopkins University Medical School in Baltimore, MD, USA. Dr. Laiho now serves as Professor of Pharmacy in the CDR where she leads the Cancer and Chemical Biology Group. She has authored approximateky 100 research articles and has received numerous awards. The group of Dr. Laiho focuses on the relevance and implications of cellular DNA damage responses in cancer.

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