Nancy Maizels

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University of Washington
School of Medicine
Immunology
ProfessorAppointed: 2000
Professional Headshot of Nancy Maizels

Mailing Address

1959 N.E. Pacific Street
Box 357650
Seattle, Washington 98195-7650
United States

Contact Information

Phone: (206) 221-6876
Fax: (206) 221-6781
maizels@u.washington.edu
http://depts.washington.edu/maizels9/

Qualifications

Ph.D., Harvard University, Biophysics, 1974.
A.B., University of California, Berkeley, Biology-Physics, 1968.
Harvard University, Junior Fellow of the Society of Fellows.

Expertise and Research Interests

Our laboratory studies the mechanisms of DNA recombination and repair in mammalian B cells. 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. Some projects focus on elucidating mutagenic pathways and harnessing natural mechanisms of mutagenesis and repair, to accelerate antibody evolution; and other projects ask how alternative structures formed by G-rich regions (G4 DNA) contribute to genomic instability and regulation of gene expression. We employ a great variety of experimental tools, spanning biochemistry, genetics and cell biology. Our work has defined new mechanisms of genomic instability leading to cancer, and generated new approaches to vector-free gene therapy.

Other Expertise

I am the Director of the Molecular Medicine Training Program, a program designed to train Ph.D. students in basic biomedical sciences to solve problems relevant to human disease. The UW MMTP is one of 13 such programs in the US funded by the Howard Hughes Medical Institute. To learn more, go to:

Future Research

Ig gene diversification in the immune response: We continue to study the pathways of somatic hypermutation, switch recombination and gene conversion in cellular and molecular detail; and we are applying our understanding of the mechanism of hypermutation to accelerated antibody evolution in vitro.

Genomic instability of G-rich regions and cancer: We are building on genomic analysis to learn how formation of G4 DNA promotes instability of G-rich regions and cancer; and how conserved repair factors maintain these regions.

Gene therapy: We are harnessing our mechanistic understanding of homology-directed repair to carry out targeted gene therapy of human genetic diseases

Keywords

COS Keywords:

Biochemistry, Biophysics, Cancer Genetics, DNA Repair, Genetics, Immune System, Immunology.

Additional Terms:

Aging, Antibody Evolution in Vitro, B Lymphocytes, Cancer, DNA Repair, Gene Therapy, Immunoglobulin Switch Recombination, MRE11 AP Lyase, RecQ Helicases, Recombination, Somatic Hypermutation.

Memberships

American Association of Immunologists
American Society for Biochemistry and Molecular Biology
FASEB
Genetics Society of America

Previous Positions

1987-2000, Professor, Yale University, Molecular Biophysics & Biochemistry and Genetics
Professor, Yale University, School of Medicine, Molecular Biophysics and Biochemistry, and Genetics

Funding Received

  • R01 GM39799: Molecular Mechanisms of Isotype Switch Recombination, $208,000/yr, 2006 to 2010.
  • P01 CA77852: Recombinational Repair Mechanisms/Genetic Instability of Werner Syndrome, $143,000/yr, 2004 to 2009.
  • R01 GM41712: Mechanisms of Somatic Mutation of Immunoglobulin Genes, $214,000/yr, 2002 to 2007.
  • R01 GM65988: Dynamics and Function of G4 DNA, $195,000/yr, 2002 to 2008.

Publications

  • Duquette, M.L., Huber, M.D., Maizels, N. (2007) G-rich proto-oncogenes are targeted for genomic instability in B cell lymphomas, Cancer Res., 67, 2586
  • Cummings, W.J., Yabuki, M., Ordinario, E.C., Bednarski, D.W., Quay, S., Maizels, N. (2007) Chromatin structure regulates gene conversion, PLoS Biology, In Press
  • Vallur, A.C., Yabuki, M., Larson, E.D., Maizels, N. (2006) AID in antibody perfection, Cell Mol. Life Sci., 64, 555
  • Eddy, J., Maizels, N. (2006) Gene function correlates with potential for G4 DNA formation in the human genome, Nucl. Acids Res., 34, 3887
  • Maizels, N. (2006) Dynamic role for G4 DNA in the biology of eukaryotic cells, Nature Struc. Mol. Biol., 13, 1055
  • Huber, M.D., Duquette, M.L., Shiels, J.C., Maizels, N. (2006) A conserved G4 DNA binding domain in RecQ family helicases, J. Mol. Biol., 358, 1071
  • Duquette ML, Pham P, Goodman MF, Maizels N (Sep 2005) AID binds to transcription-induced structures in c-MYC that map to regions associated with translocation and hypermutation., Oncogene, 24 (38), 5791-8 Abstract
  • Yabuki M, Fujii MM, Maizels N (Jul 2005) The MRE11-RAD50-NBS1 complex accelerates somatic hypermutation and gene conversion of immunoglobulin variable regions., Nature Immunology, 6 (7), 730-6 Abstract
  • Larson ED, Duquette ML, Cummings WJ, Streiff RJ, Maizels N (Mar 2005) MutSalpha binds to and promotes synapsis of transcriptionally activated immunoglobulin switch regions., Current Biology : Cb, 15 (5), 470-4 Abstract
  • Larson, E.D., Cummings, W.J., Bednarski, D.W., Maizels, N. (2005) MRE11/RAD50 cleaves DNA in the AID/UNG-dependent pathway of immunoglobulin gene diversification, Molecular Cell, 19, 367
  • Maizels, N. (2005) Immunoglobulin gene diversification, Annu. Rev. Genetics, 39, 23
  • Duquette ML, Handa P, Vincent JA, Taylor AF, Maizels N (Jul 2004) Intracellular transcription of G-rich DNAs induces formation of G-loops, novel structures containing G4 DNA., Genes & Development, 18 (13), 1618-29 Abstract
  • Larson, E.D., Maizels, N. (2004) Transcription-coupled mutagenesis by the DNA deaminase AID, Genome Biol., 5, 211
  • Cocco, M., Hanakahi, L.A., Huber, M.D., Maizels, N. (2003) Specific interactions of distamycin with G quadruplex DNA, Nucl. Acids Res., 31, 2944
  • Maizels, N. (2003) Yin outwits Yang at the IgE locus, Nature Immunol., 4, 7
  • Huber, M.D., Lee, D.C., Maizels, N. (2002) G4 DNA unwinding by BLM and Sgs1p: substrate-specificity and substrate-specific inhibition, Nucl. Acids Res., 30, 3954
  • Kong Q, Maizels N, DNA breaks in hypermutating immunoglobulin genes: evidence for a break-and-repair pathway of somatic hypermutation, Genetics, 158, 369-378, 2001
  • Wu X, Maizels N, Substrate-specific inhibition of RecQ helicase, Nucleic Acids Research, 29, 1765-1771, 2001
  • Kong Q, Maizels N, Breaksite batch mapping, a rapid method for assay and identification of DNA breaksites in mammalian cells, Nucleic Acids Research, 29, E33, 2001
  • Sun, H., Yabuki, A., Maizels, N. (2001) A human nuclease specific for G4 DNA, Proc. Natl. Acad. Sci. USA, 98, 12444
  • Eversole A, Maizels N, hnRNP D: a mammalian protein that binds telomeric tails, Molecular and Cellular Biology, 20, 5425-5432, 1 Aug 2000
  • Hanakahi LA, Maizels N, Transcriptional activation by LR1 at the Eµ enhancer and switch region sites, Nucleic Acids Research, 28, 2651-2657, 15 Jul 2000
  • Liu Y, Maizels N, Coordinated response of mammalian Rad51 and Rad52 to DNA damage, EMBO Reports, 1(1), 85-90, 1 Jul 2000
  • Maizels N, Secret sharers in the immune system: a novel RNA editing activity links switch recombination and somatic hypermutation, Genomebiology.com, 1(4), REVIEWS1025, 2000 Abstract
  • Hanakahi LA, Bu Z, Maizels N, The C-terminal domain of nucleolin accelerates nucleic acid annealing, Biochemistry, 39, 15493-15499, 2000
  • Gallouzi IE, Brennan CM, Stenberg MG, Swanson MS, Eversole A, Maizels N, Steitz JA, HuR binding to cytoplasmic mRNA is perturbed by heat shock, Proceedings of the National Academy of Sciences (USA), 97, 3073-3078, 2000
  • Liu Y, Li M, Lee EY, Maizels N, Localization and dynamic relocalization of mammalian Rad52 during the cell cycle and in response to DNA damage, Current Biology, 9(17), 975-8, September 1999 Abstract
  • Maizels N, Weiner AM, Yue D, Shi PY, New evidence for the genomic tag hypothesis: archaeal CCA-adding enzymes and tDNA substrates, Biological Bulletin, 196(3), 331-3; discussion 33, June 1999 Abstract
  • Maizels N, Immunoglobulin class switch recombination: will genetics provide new clues to mechanism?, American Journal of Human Genetics, 64(5), 1270-5, May 1999 Abstract
  • Sun H, Bennett RJ, Maizels N, The Saccharomyces cerevisiae Sgs1 helicase efficiently unwinds G-G paired DNAs, Nucleic Acids Research, 27(9), 1978-84, May 1999 Abstract
  • Weiner AM, Maizels N, A deadly double life [comment], Science, 284(5411), 63-4, April 1999 Abstract
  • Harris RS, Kong Q, Maizels N, Somatic hypermutation and the three R's: repair, replication and recombination, Mutation Research, 436(2), 157-78, March 1999 Abstract
  • Dempsey LA, Sun H, Hanakahi LA, Maizels N, G4 DNA binding by LR1 and its subunits, nucleolin and hnRNP D, A role for G-G pairing in immunoglobulin switch recombination, Journal of Biological Chemistry, 274(2), 1066-71, Jan 1999 Abstract
  • Li MJ, Maizels N, Activation and targeting of immunoglobulin switch recombination by activities induced by EBV infection, Journal of Immunology, 163(12), 6659-6664, 1999
  • Yue D, Weiner AM, Maizels N, The CCA-adding enzyme has a single active site, Journal of Biological Chemistry, 273(45), 29693-700, November 1998 Abstract
  • Peakman MC, Maizels N, Localization of splenic B cells activated for switch recombination by in situ hybridization with Igamma1 switch transcript and Rad51 probes, Journal of Immunology, 161(8), 4008-15, October 1998 Abstract
  • Dempsey LA, Hanakahi LA, Maizels N, A specific isoform of hnRNP D interacts with DNA in the LR1 heterodimer: canonical RNA binding motifs in a sequence-specific duplex DNA binding protein, Journal of Biological Chemistry, 273(44), 29224-9, October 1998 Abstract
  • Sun H, Karow JK, Hickson ID, Maizels N, The Bloom's syndrome helicase unwinds G4 DNA, Journal of Biological Chemistry, 273(42), 27587-92, October 1998 Abstract
  • Kong Q, Zhao L, Subbaiah S, Maizels N, A lambda 3' enhancer drives active and untemplated somatic hypermutation of a lambda 1 transgene., Journal of Immunology, 161(1), 294-301, 1 Jul 1998 Abstract
  • Shi P Y, Maizels N, Weiner A M, CCA addition by tRNA nucleotidyltransferase: polymerization without translocation?, Embo Journal, 17(11), 3197-206, 1 Jun 1998 Abstract
  • Dempsey L A, Li M J, DePace A, Bray-Ward P, Maizels N, The human HNRPD locus maps to 4q21 and encodes a highly conserved protein., Genomics, 49(3), 378-84, 1 May 1998 Abstract
  • Kong Q, Harris R S, Maizels N, Recombination-based mechanisms for somatic hypermutation., Immunological Reviews, 162, 67-76, April 1998 Abstract
  • Shi P Y, Weiner A M, Maizels N, A top-half tDNA minihelix is a good substrate for the eubacterial CCA-adding enzyme., Rna, 4(3), 276-84, March 1998 Abstract
  • Shi P Y, Maizels N, Weiner A M, Recovery of soluble, active recombinant protein from inclusion bodies., Biotechniques, 23(6), 1036-8, December 1997 Abstract
  • Li M J, Maizels N, Nuclear Rad51 foci induced by DNA damage are distinct from Rad51 foci associated with B cell activation and recombination., Experimental Cell Research, 237(1), 93-100, 25 Nov 1997 Abstract
  • Hanakahi L A, Dempsey L A, Li M J, Maizels N, Nucleolin is one component of the B cell-specific transcription factor and switch region binding protein, LR1., Proceedings of the National Academy of Sciences (USA), 94(8), 3605-10, 15 Apr 1997 Abstract
  • Li M J, Chung W, Maizels N, Developmental specificity of immunoglobulin heavy chain switch region recombination activities., Molecular Immunology, 34(3), 201-8, February 1997 Abstract
  • Li M J, Peakman M C, Golub E I, Reddy G, Ward D C, Radding C M, Maizels N, Rad51 expression and localization in B cells carrying out class switch recombination., Proceedings of the National Academy of Sciences (USA), 93(19), 10222-7, 17 Sep 1996 Abstract
  • Yue D, Maizels N, Weiner A M, CCA-adding enzymes and poly(A) polymerases are all members of the same nucleotidyltransferase superfamily: characterization of the CCA-adding enzyme from the archaeal hyperthermophile Sulfolobus shiba, Rna, 2(9), 895-908, September 1996 Abstract
  • Maizels N, Somatic hypermutation: how many mechanisms diversify V region sequences?, Cell, 83(1), 9-12, 6 Oct 1995 Abstract
  • Bulfone-Paus S, Dempsey L A, Maizels N, Host factors LR1 and Sp1 regulate the Fp promoter of Epstein-Barr virus., Proceedings of the National Academy of Sciences (USA), 92(18), 8293-7, 29 Aug 1995 Abstract
  • Hengstschlager M, Maizels N, Leung H, Targeting and regulation of immunoglobulin gene somatic hypermutation and isotype switch recombination., Progress In Nucleic Acid Research and Molecular Biology, 50, 67-99, 1995 Abstract
  • Hengstschlager M, Maizels N, Isotype exclusion in lambda 1 transgenic mice depends on transgene copy number and diminishes with down-regulation of transgene transcripts., European Journal of Immunology, 25(1), 187-91, January 1995 Abstract
  • Maizels N, Weiner A M, Phylogeny from function: evidence from the molecular fossil record that tRNA originated in replication, not translation., Proceedings of the National Academy of Sciences (USA), 91(15), 6729-34, 19 Jul 1994 Abstract
  • Hengstschlager M, Williams M, Maizels N, A lambda 1 transgene under the control of a heavy chain promoter and enhancer does not undergo somatic hypermutation., European Journal of Immunology, 24(7), 1649-56, July 1994 Abstract
  • Weiner A M, Maizels N, Molecular evolution. Unlocking the secrets of retroviral evolution., Current Biology, 4(6), 560-3, 1 Jun 1994 Abstract
  • Brys A, Maizels N, LR1 regulates c-myc transcription in B-cell lymphomas., Proceedings of the National Academy of Sciences (USA), 91(11), 4915-9, 24 May 1994 Abstract
  • Leung H, Maizels N, Regulation and targeting of recombination in extrachromosomal substrates carrying immunoglobulin switch region sequences., Molecular and Cellular Biology, 14(2), 1450-8, February 1994 Abstract
  • Maizels N, Preimmune diversification creates a repertoire while somatic hypermutation fine-tunes affinity--implications for the processes of mutation., Research In Immunology, 144(6-7), 459-63, July 1993 Abstract
  • Williams M, Hanakahi L A, Maizels N, Purification and properties of LR1, an inducible DNA binding protein from mammalian B lymphocytes., Journal of Biological Chemistry, 268(18), 13731-7, 25 Jun 1993 Abstract
  • David V, Folk N L, Maizels N, Germ line variable regions that match hypermutated sequences in genes encoding murine anti-hapten antibodies., Genetics, 132(3), 799-811, November 1992 Abstract
  • Williams M, Brys A, Weiner A M, Maizels N, A rapid method for determining the molecular weight of a protein bound to nucleic acid in a mobility shift assay., Nucleic Acids Research, 20(18), 4935-6, 25 Sep 1992 Abstract
  • Leung H, Maizels N, Transcriptional regulatory elements stimulate recombination in extrachromosomal substrates carrying immunoglobulin switch-region sequences., Proceedings of the National Academy of Sciences (USA), 89(9), 4154-8, 1 May 1992 Abstract
  • Williams M, Maizels N, LR1, a lipopolysaccharide-responsive factor with binding sites in the immunoglobulin switch regions and heavy-chain enhancer., Genes and Development, 5(12A), 2353-61, December 1991 Abstract
  • Weiner A M, Maizels N, RNA editing: guided but not templated?, Cell, 61(6), 917-20, 15 Jun 1990 Abstract
  • Maizels N, To understand function, study structure., Cell, 60(6), 887-9, 23 Mar 1990 Abstract
  • Maizels N, Might gene conversion be the mechanism of somatic hypermutation of mammalian immunoglobulin genes?, Trends In Genetics, 5(1), 4-8, January 1989 Abstract
  • Li, M.-J., Peakman, M.-C., Golub, E.I., Reddy, G., Ward, D.C., Radding, C.M., and Maizels, N. 1996. Rad51 expression and localization in B cells carrying out class switch recombination. Proc. Nat. Acad. Sci. USA 93:10222-10227

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Last Updated: 7/20/2007

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