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Department of Immunology Dr. Maizels was an undergraduate at the University of California at Berkeley. She received her Ph.D. from Harvard University, and she continued at Harvard as a Junior Fellow of the Society of Fellows. She was a Professor in the Departments of Molecular Biophysics & Biochemistry and Genetics at Yale University School of Medicine before coming to the University of Washington in Fall, 2000. Research in the Maizels Lab: B cells diversify the sequences and structure of their immunoglobulin genes, to respond dynamically to infection by pathogenic microorganisms, so these cells provide insights in real time and physiological contexts into mechanisms of DNA mutagenesis and repair in all cell types. We study these mechanisms in molecular and subcellular detail. Some projects focus on elucidating mutagenic pathways; others on harnessing natural mechanisms of mutagenesis to accelerate antibody evolution; and others on learning how alternative structures formed by G-rich regions (G4 DNA) contribute to genomic instability and cancer. We employ a great variety of experimental tools, spanning biochemistry, genetics and cell biology. Our research has defined new mechanisms of genomic instability leading to cancer, and generated new approaches to vector-free gene therapy. Graduate students currently training in the Maizels Lab: Amber Caracol, Diem-Hang Nguyen-Tran (MCB), and Quy Le. Selected publications: Yabuki, M., Fujii, M.M., Maizels N. 2005. The MRE11/RAD50/NBS1 complex accelerates somatic hypermutation and gene conversion of immunoglobulin variable regions. Nature Immunol. 6:730-736. Larson, E.D., Duquette, M.L., Cummings, W.J., Streiff, R.J. and Maizels, N. 2005. MutSa binds to and promotes synapsis of transcriptionally activated immunoglobulin switch regions. Curr. Biol. 15:470-474. Larson, E.D., Cummings, W.J., Bednarski, D.W. and Maizels, N. 2005. MRE11/RAD50 cleaves DNA in the AID/UNG-dependent pathway of immunoglobulin gene diversification. Mol. Cell 19:367-375. Maizels, N. 2005. Immunoglobulin gene diversification. Annu. Rev. Genetics 39:23-46. Huber, M.D., Duquette, M.L., Shiels, J.C. and Maizels, N. 2006. A conserved G4 DNA binding domain in RecQ family helicases. J. Mol. Biol. 358:1071-80. Eddy, J. and Maizels, N. 2006. Gene function correlates with potential for G4 DNA formation in the human genome. Nucleic Acids Res. 34: 3887-3896. Maizels, N. 2006. Dynamic roles for G4 DNA in the biology of eukaryotic cells. Nat. Struct. Mol. Biol. 13:1055-1059. Duquette, M.L., Huber, M.D. and Maizels, N. 2007. G-rich proto-oncogenes are targeted for genomic instability in B cell lymphomas. Cancer Res. 67:2586-2594. Cummings, W.J., Yabuki, M., Ordinario, E.C., Bednarski, D.W., Quay, S. and Maizels, N. 2007. Chromatin structure regulates gene conversion. PLoS Biology, 5:e246. Vallur, A.C. and Maizels, N. 2008. Activities of human exonuclease 1 that promote cleavage of transcribed immunoglobulin switch regions. Proc. Natl. Acad. Sci. USA 105:16508-16512. Cummings, W.J., Bednarski, D.W. and Maizels N. 2008. Genetic variation stimulated by epigenetic modification. PloS ONE 3:4075. Yabuki, M.*, Ordinario, E.C.*, Cummings, W.J., Fujii, M.M. and Maizels, N. 2009. E2A acts in cis in G1 phase of cell cycle to promote Ig gene diversification (*joint first authors). J. Immunol. 182:408-415.
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Profile Updated 8/30/10
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