NGEC Principal Investigator
Department of Immunology
University of Washington
1959 NE Pacific St.
HSB, H479, Box 357650
Seattle, WA 98195-7650
Tel: (206) 221-6876 Fax: (206) 221-6781
E-mail Dr. Maizels
Dr. Maizels graduated from the University of California, Berkeley with her AB and earned her PhD from Harvard University. She taught biochemistry for 13 years at Yale University School of Medicine, where she also directed the Cellular and Molecular Biology Pre-doctoral Training Program. Dr. Maizels is a founder and director of the University of Washington’s Molecular Medicine Training Program.
Dr. Maizels is the NGEC principal investigator in the area of Targeted Gene Repair by Homologous Recombination.
“The power of our approach to gene therapy is that we are using the same mechanisms of repair that cells have perfected over billions of years of evolution.”The current understanding of the mechanism of homology-directed repair is very sophisticated. As participants in the NGEC, the Maizels lab will harness this understanding to promote correction of genetic defects in situ. Questions it seeks to answer include: Can we increase the efficiency of homology-directed repair? Can we minimize the deleterious consequences of nuclease-targeted therapies?
Key lab personnel carrying out this research include: Jason Cummings, PhD; Luther Davis, PhD; and Munehisa Yabuki, PhD.
The Maizels laboratory studies mechanisms of immunoglobulin gene diversification, genomic instability, and homology-directed gene correction. The lab has made significant recent advances by defining the essential steps in the molecular mechanism of immunoglobulin gene diversification, and by identifying novel structures form in G-rich DNA and elucidating how they promote genomic instability.
Jason Cummings, post doctoral fellow in Nancy Maizel's lab.
Cummings, W.J., Yabuki, M., Ordinario, E.C., Bednarski, D.W., Quay, S. and Maizels, N. 2007. Chromatin structure regulates gene conversion. PLoS Biol. 5: e246.
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.
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.
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.
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. MutSalpha binds to and promotes synapsis of transcriptionally activated immunoglobulin switch regions. Curr. Biol. 15: 470-474.
Duquette, M.L., Handa, P., Vincent, J., Taylor, A.F., and Maizels, N. 2004. Intracellular transcription of G-rich DNAs induces formation of G-loops, novel structures containing G4 DNA. Genes Dev. 18: 1618-1629.