Chan, Kin - University of Ottawa - Department of Biochemistry, Microbiology and Immunology

个人简介

B.S., Caltech (1998) Ph.D., University of Washington/Fred Hutchinson Cancer Research Center (2008 Postdoctoral Fellowship, National Institute of Environmental Health Sciences (2016)

研究领域

Cancer remains a major public health challenge in Canada. The Canadian Cancer Society estimates that 2 in 5 Canadians will develop cancer and 1 in 4 will die from it. Cancer results from alterations in a cell’s DNA, called mutations, which can lead to uncontrolled cell growth and division. Therefore, to understand the origin of cancer at its most fundamental level, we must understand the origin of mutations. Mutations are caused by the reaction of DNA with chemical, enzymatic, or physical agents called mutagens. Each mutagen creates a characteristic mutation signature in DNA, which includes the DNA sequence context(s) that are targeted preferentially and the resulting pattern of DNA base substitution(s). Some of these signatures have been identified in cancer samples. However, the mutation signatures of many carcinogens and mutagens remain undetermined. Dr. Chan’s research program combines leading edge techniques in molecular biology, genetics, and bioinformatics to elucidate the mutation signatures created by high-priority known or suspected carcinogens identified by the International Agency for Research on Cancer (IARC), which is part of the World Health Organization. With a better understanding of the origin of mutations, it will be possible to devise better cancer prevention, diagnosis, and treatment strategies. Better prevention reduces cancer incidence, while improved diagnosis in populations that are genetically vulnerable or have been previously exposed to carcinogen(s) enables earlier detection of treatable disease. More specific, less toxic treatments with fewer side effects will improve survivorship for cancer patients, and maintain better quality of life for themselves and their loved ones. These improved strategies would substantially reduce the public health burden of cancer in Canada and the world at large. Current research topics include: Deciphering the mutation signatures created by high-priority known or suspected carcinogens. Characterizing genetic perturbations that significantly affect these mutation signatures. Quantifying the presence of these mutation signatures in cancer genomic and exomic mutation data sets.

近期论文

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Chan K, Roberts SA, Klimczak LJ, Sterling JF, Saini N, Malc EP, Kim Jaegil, Kwiatkowski DJ, Fargo DC, Mieczkowski PA, Getz G, and Gordenin DA. (2015) An APOBEC3A hypermutation signature is distinguishable from the signature of background mutagenesis by APOBEC3B in human cancers. Nat Genet. 47(9):1067-72. Chan K, Gordenin DA. (2015) Clusters of Multiple Mutations: Incidence and Molecular Mechanisms. Annu Rev Genet. 49:243-67.Chan K, Resnick MA, and Gordenin DA. (2013) The choice of nucleotide inserted opposite abasic sites formed within chromosomal DNA reveals the polymerase activities participating in translesion DNA synthesis. DNA Repair. 12(11):878-89. Chan K, Sterling JF, Roberts SA, Bhagwat AS, Resnick MA, and Gordenin DA. (2012) Base Damage within Single-Strand DNA Underlies In Vivo Hypermutability Induced by a Ubiquitous Environmental Agent. PLoS Genet. 8(12): e1003149. Chan K, Goldmark JP, and Roth MB. (2010) Suspended animation extends survival limits of Caenorhabditis elegans and Saccharomyces cerevisiae at low temperature. Mol Biol Cell. 21(13): 2161-71. Chan K, Roth MB. (2008) Anoxia-induced suspended animation in budding yeast as an experimental paradigm for studying oxygen-regulated gene expression. Eukaryot Cell. 7(10): 1795-808. Chan K, Meng QC, Johansson JS, Eckenhoff RG. (2002) Low affinity analytical chromatography: a new method for measuring inhaled anesthetic binding to isolated proteins. Anal Biochem. 301(2): 308-13. Eckenhoff MF, Chan K, Eckenhoff RG. (2002) Multiple binding targets for inhaled anesthetics in the mammalian brain. J. Pharmacol. Exp. Therap. 300(1): 172-9. Trask BJ, Massa H, Brand-Arpon V, Chan K, Friedman C, Nguyen OT, Eichler E, van den Engh G, Rouquier S, Shizuya H, Giorgi D. (1998) Large multi-chromosomal duplications encompass many members of the olfactory receptor gene family in the human genome. Hum Mol Genet. 7(13): 2007-20.