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Department of Immunology Dr. Maizels was an undergraduate at the University of California at 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: Johanna Eddy, Nicolle Hamilton and Amber West. 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. MutSα 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. Molecular Cell 19:367-375. Maizels, N. 2005. Immunoglobulin gene diversification. Annu. Rev. Genetics 39:23-46. Duquette, M.L., Pham, P., Goodman, M.F. and Maizels, N. 2005. AID binds to transcription-induced structures in c-MYC that map to regions associated with translocation and hypermutation. Oncogene 24: 5791-5798. 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. 358:1071-1080. 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. Vallur, A.C., Yabuki, M., Larson, E.D. and Maizels, N. 2007. AID in antibody perfection. Cell Mol. Life Sci. 64: 555-655. 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, in press. COS Expertise
Profile Updated 7/20/07
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