Nancy Maizels, PhD

NGEC Principal Investigator

Professor of Immunology and Biochemistry
Director, Molecular Medicine Program

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

Email Dr. Maizels

Dr. Maizels is a professor of immunology and biochemistry at the University of Washington. Dr. Maizels's research focuses on mechanisms of genomic instability in mammalian cells, particularly activated B cells, and she is internationally recognized for her work on mechanisms of mutagenesis and recombination. Her laboratory has ongoing work on the basic mechanisms of DNA repair and somatic hypermutation, the application of somatic hypermutation as a tool for in vitro antibody engineering and manipulation of repair mechanisms to enhance recombination at nuclease-induced double strand breaks.

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."
Nancy Maizels

Areas of Expertise

Immune response
DNA repair
Cancer

Research Interests

Mechanisms of immunoglobulin gene diversification
Genomic instability
Homology-directed gene correction

Overview of the Maizels Lab

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.

NGEC Research

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 personnel carrying out this research include Luther Davis (postdoctoral fellow), Olivier Humbert (postdoctoral fellow) and Diem-Hang Nguyen-Tran (graduate student).

Publications

2013

Kiianitsa K, Maizels N. 2013. A rapid and sensitive assay for DNA-protein covalent complexes in living cells.. Nucleic Acids Res.

Maizels N, Gray LT. 2013. The g4 genome.. PLoS Genet. 9(4):e1003468.

2012

Humbert O, Davis L, Maizels N. 2012. Targeted gene therapies: tools, applications, optimization.. Critical reviews in biochemistry and molecular biology. 47(3):264-81.

Yabuki M, Cummings JW, Leppard JB, Immormino RM, Wood CL, Allison DS, Gray PW, Tjoelker LW, Maizels N. 2012. Antibody Discovery Ex Vivo Accelerated by the LacO/LacI Regulatory Network.. PloS one. 7(4):e36032.

Maizels N. 2012. G4 motifs in human genes.. Ann N Y Acad Sci. 1267(1):53-60.

Humbert O, Maizels N. 2012. Epigenetic modification of the repair donor regulates targeted gene correction.. Mol Ther Nucleic Acids. 1:e49.

2011

Davis L, Maizels N. 2011. DNA nicks promote efficient and safe targeted gene correction.. PloS one. 6(9):e23981.

Davis L, Maizels N. 2011. G4 DNA: at risk in the genome.. The EMBO journal. 30(19):3878-9.

Sacho EJ, Maizels N. 2011. MRE11/RAD50 cleaves 3'-phosphotyrosyl bonds and resects DNA to repair damage caused by Topoisomerase 1 poisons.. The Journal of biological chemistry.

2010

Hamilton NK, Maizels N. 2010. MRE11 function in response to topoisomerase poisons is independent of its function in double-strand break repair in Saccharomyces cerevisiae.. PloS one. 5(10):e15387.

Vallur AC, Maizels N. 2010. Complementary roles for exonuclease 1 and Flap endonuclease 1 in maintenance of triplet repeats.. The Journal of biological chemistry. 285(37):28514-9.

Vallur AC, Maizels N. 2010. Distinct activities of exonuclease 1 and flap endonuclease 1 at telomeric g4 DNA.. PloS one. 5(1):e8908.

2009

Ordinario EC, Yabuki M, Handa P, Cummings JW, Maizels N. 2009. RAD51 paralogs promote homology-directed repair at diversifying immunoglobulin V regions.. BMC molecular biology. 10:98.

Ordinario EC, Yabuki M, Larson RP, Maizels N. 2009. Temporal regulation of Ig gene diversification revealed by single-cell imaging.. Journal of immunology (Baltimore, Md. : 1950). 183(7):4545-53.

Eddy J, Maizels N. 2009. Selection for the G4 DNA motif at the 5' end of human genes.. Molecular carcinogenesis. 48(4):319-25.

McConnell Smith A, Takeuchi R, Pellenz S, Davis L, Maizels N, Monnat RJ, Stoddard BL. 2009. Generation of a nicking enzyme that stimulates site-specific gene conversion from the I-AniI LAGLIDADG homing endonuclease.. Proceedings of the National Academy of Sciences of the United States of America. 106(13):5099-104.

Yabuki M, Ordinario EC, Cummings JW, Fujii MM, Maizels N. 2009. E2A acts in cis in G1 phase of cell cycle to promote Ig gene diversification.. Journal of immunology (Baltimore, Md. : 1950). 182(1):408-15.

2008

Cummings JW, Bednarski DW, Maizels N. 2008. Genetic variation stimulated by epigenetic modification.. PloS one. 3(12):e4075.

Larson ED, Bednarski DW, Maizels N. 2008. High-fidelity correction of genomic uracil by human mismatch repair activities.. BMC molecular biology. 9:94.

Vallur AC, Maizels N. 2008. Activities of human exonuclease 1 that promote cleavage of transcribed immunoglobulin switch regions.. Proceedings of the National Academy of Sciences of the United States of America. 105(43):16508-12.

Maizels N. 2008. Genomic stability: FANCJ-dependent G4 DNA repair.. Current biology : CB. 18(14):R613-4.

Eddy J, Maizels N. 2008. Conserved elements with potential to form polymorphic G-quadruplex structures in the first intron of human genes.. Nucleic acids research. 36(4):1321-33.

2007

Cummings JW, Yabuki M, Ordinario EC, Bednarski DW, Quay S, Maizels N. 2007. Chromatin structure regulates gene conversion.. PLoS biology. 5(10):e246.

Duquette ML, Huber MD, Maizels N. 2007. G-rich proto-oncogenes are targeted for genomic instability in B-cell lymphomas.. Cancer research. 67(6):2586-94.

Vallur AC, Yabuki M, Larson ED, Maizels N. 2007. AID in antibody perfection.. Cellular and molecular life sciences : CMLS. 64(5):555-65.

2006

Maizels N. 2006. Dynamic roles for G4 DNA in the biology of eukaryotic cells.. Nature structural & molecular biology. 13(12):1055-9.

Eddy J, Maizels N. 2006. Gene function correlates with potential for G4 DNA formation in the human genome.. Nucleic acids research. 34(14):3887-96.

Huber MD, Duquette ML, Shiels JC, Maizels N. 2006. A conserved G4 DNA binding domain in RecQ family helicases.. Journal of molecular biology. 358(4):1071-80.

2005

Larson ED, Cummings JW, Bednarski DW, Maizels N. 2005. MRE11/RAD50 cleaves DNA in the AID/UNG-dependent pathway of immunoglobulin gene diversification.. Molecular cell. 20(3):367-75.

Maizels N. 2005. Immunoglobulin gene diversification.. Annual review of genetics. 39:23-46.

Duquette ML, Pham P, Goodman MF, Maizels N. 2005. AID binds to transcription-induced structures in c-MYC that map to regions associated with translocation and hypermutation.. Oncogene. 24(38):5791-8.

Yabuki M, Fujii MM, Maizels N. 2005. The MRE11-RAD50-NBS1 complex accelerates somatic hypermutation and gene conversion of immunoglobulin variable regions.. Nature immunology. 6(7):730-6.

Larson ED, Duquette ML, Cummings JW, Streiff RJ, Maizels N. 2005. MutSalpha binds to and promotes synapsis of transcriptionally activated immunoglobulin switch regions.. Current biology : CB. 15(5):470-4.

2004

Duquette ML, Handa P, Vincent JA, Taylor AF, Maizels N. 2004. Intracellular transcription of G-rich DNAs induces formation of G-loops, novel structures containing G4 DNA.. Genes & development. 18(13):1618-29.

Larson ED, Maizels N. 2004. Transcription-coupled mutagenesis by the DNA deaminase AID.. Genome biology. 5(3):211.

2003

Cocco MJ, Hanakahi LA, Huber MD, Maizels N. 2003. Specific interactions of distamycin with G-quadruplex DNA.. Nucleic acids research. 31(11):2944-51.

Maizels N. 2003. Yin outwits Yang at the IgE locus.. Nature immunology. 4(1):7-8.

2002

Huber MD, Lee DC, Maizels N. 2002. G4 DNA unwinding by BLM and Sgs1p: substrate specificity and substrate-specific inhibition.. Nucleic acids research. 30(18):3954-61.

2001

Kong Q, Maizels N. 2001. Breaksite batch mapping, a rapid method for assay and identification of DNA breaksites in mammalian cells.. Nucleic acids research. 29(6):E33.

Sun H, Yabuki A, Maizels N. 2001. A human nuclease specific for G4 DNA.. Proceedings of the National Academy of Sciences of the United States of America. 98(22):12444-9.

Kong Q, Maizels N. 2001. DNA breaks in hypermutating immunoglobulin genes: evidence for a break-and-repair pathway of somatic hypermutation.. Genetics. 158(1):369-78.

Wu X, Maizels N. 2001. Substrate-specific inhibition of RecQ helicase.. Nucleic acids research. 29(8):1765-71.

2000

Liu Y, Maizels N. 2000. Coordinated response of mammalian Rad51 and Rad52 to DNA damage.. EMBO reports. 1(1):85-90.

Maizels N. 2000. Secret sharers in the immune system: a novel RNA editing activity links switch recombination and somatic hypermutation.. Genome biology. 1(4):REVIEWS1025.

Hanakahi LA, Bu Z, Maizels N. 2000. The C-terminal domain of nucleolin accelerates nucleic acid annealing.. Biochemistry. 39(50):15493-9.

Hanakahi LA, Maizels N. 2000. Transcriptional activation by LR1 at the Emu enhancer and switch region sites.. Nucleic acids research. 28(14):2651-7.

Eversole A, Maizels N. 2000. In vitro properties of the conserved mammalian protein hnRNP D suggest a role in telomere maintenance.. Molecular and cellular biology. 20(15):5425-32.

Gallouzi IE, Brennan CM, Stenberg MG, Swanson MS, Eversole A, Maizels N, Steitz JA. 2000. HuR binding to cytoplasmic mRNA is perturbed by heat shock.. Proceedings of the National Academy of Sciences of the United States of America. 97(7):3073-8.

1999

Harris RS, Kong Q, Maizels N. 1999. Somatic hypermutation and the three R's: repair, replication and recombination.. Mutation research. 436(2):157-78.

Dempsey LA, Sun H, Hanakahi LA, Maizels N. 1999. G4 DNA binding by LR1 and its subunits, nucleolin and hnRNP D, A role for G-G pairing in immunoglobulin switch recombination.. The Journal of biological chemistry. 274(2):1066-71.

Li MJ, Maizels N. 1999. Activation and targeting of immunoglobulin switch recombination by activities induced by EBV infection.. Journal of immunology (Baltimore, Md. : 1950). 163(12):6659-64.

Liu Y, Li M, Lee EY, Maizels N. 1999. Localization and dynamic relocalization of mammalian Rad52 during the cell cycle and in response to DNA damage.. Current biology : CB. 9(17):975-8.

Maizels N, Weiner AM, Yue D, Shi PY. 1999. New evidence for the genomic tag hypothesis: archaeal CCA-adding enzymes and tDNA substrates.. The Biological bulletin. 196(3):331-3;discussion333-4.

Weiner AM, Maizels N. 1999. The genomic tag hypothesis: modern viruses as molecular fossils of ancient strategies for genomic replication, and clues regarding the origin of protein synthesis.. The Biological bulletin. 196(3):327-8;discussion329-30.

Kong Q, Maizels N. 1999. PMS2-deficiency diminishes hypermutation of a lambda1 transgene in young but not older mice.. Molecular immunology. 36(2):83-91.

Hanakahi LA, Sun H, Maizels N. 1999. High affinity interactions of nucleolin with G-G-paired rDNA.. The Journal of biological chemistry. 274(22):15908-12.

Weiner AM, Maizels N. 1999. A deadly double life.. Science (New York, N.Y.). 284(5411):63-4.

Maizels N. 1999. Immunoglobulin class switch recombination: will genetics provide new clues to mechanism? American journal of human genetics. 64(5):1270-5.

Sun H, Bennett RJ, Maizels N. 1999. The Saccharomyces cerevisiae Sgs1 helicase efficiently unwinds G-G paired DNAs.. Nucleic acids research. 27(9):1978-84.

1998

Yue D, Weiner AM, Maizels N. 1998. The CCA-adding enzyme has a single active site.. The Journal of biological chemistry. 273(45):29693-700.

Dempsey LA, Hanakahi LA, Maizels N. 1998. 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.. The Journal of biological chemistry. 273(44):29224-9.

Peakman MC, Maizels N. 1998. Localization of splenic B cells activated for switch recombination by in situ hybridization with Igamma1 switch transcript and Rad51 probes.. Journal of immunology (Baltimore, Md. : 1950). 161(8):4008-15.

Sun H, Karow JK, Hickson ID, Maizels N. 1998. The Bloom's syndrome helicase unwinds G4 DNA.. The Journal of biological chemistry. 273(42):27587-92.

Kong Q, Zhao L, Subbaiah S, Maizels N. 1998. A lambda 3' enhancer drives active and untemplated somatic hypermutation of a lambda 1 transgene.. Journal of immunology (Baltimore, Md. : 1950). 161(1):294-301.

Shi PY, Maizels N, Weiner AM. 1998. CCA addition by tRNA nucleotidyltransferase: polymerization without translocation? The EMBO journal. 17(11):3197-206.

Dempsey LA, Li MJ, DePace A, Bray-Ward P, Maizels N. 1998. The human HNRPD locus maps to 4q21 and encodes a highly conserved protein.. Genomics. 49(3):378-84.

Kong Q, Harris RS, Maizels N. 1998. Recombination-based mechanisms for somatic hypermutation.. Immunological reviews. 162:67-76.

Shi PY, Weiner AM, Maizels N. 1998. A top-half tDNA minihelix is a good substrate for the eubacterial CCA-adding enzyme.. RNA (New York, N.Y.). 4(3):276-84.

1997

Ashburner M, Maizels N. 1997. Genomes and evolution Post-genome, pre-chromosome.. Current opinion in genetics & development. 7(6):747-9.

Shi PY, Maizels N, Weiner AM. 1997. Recovery of soluble, active recombinant protein from inclusion bodies.. BioTechniques. 23(6):1036-8.

Li MJ, Maizels N. 1997. 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.

Hanakahi LA, Dempsey LA, Li MJ, Maizels N. 1997. Nucleolin is one component of the B cell-specific transcription factor and switch region binding protein, LR1.. Proceedings of the National Academy of Sciences of the United States of America. 94(8):3605-10.

Li MJ, Chung W, Maizels N. 1997. Developmental specificity of immunoglobulin heavy chain switch region recombination activities.. Molecular immunology. 34(3):201-8.

1996

Li MJ, Peakman MC, Golub EI, Reddy G, Ward DC, Radding CM, Maizels N. 1996. Rad51 expression and localization in B cells carrying out class switch recombination.. Proceedings of the National Academy of Sciences of the United States of America. 93(19):10222-7.

Yue D, Maizels N, Weiner AM. 1996. 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 shibatae.. RNA (New York, N.Y.). 2(9):895-908.

1995

Maizels N. 1995. Somatic hypermutation: how many mechanisms diversify V region sequences? Cell. 83(1):9-12.

Bulfone-Paus S, Dempsey LA, Maizels N. 1995. Host factors LR1 and Sp1 regulate the Fp promoter of Epstein-Barr virus.. Proceedings of the National Academy of Sciences of the United States of America. 92(18):8293-7.

Hengstschläger M, Maizels N. 1995. 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.

Hengstschläger M, Maizels N, Leung H. 1995. Targeting and regulation of immunoglobulin gene somatic hypermutation and isotype switch recombination.. Progress in nucleic acid research and molecular biology. 50:67-99.

1994

Maizels N, Weiner AM. 1994. Phylogeny from function: evidence from the molecular fossil record that tRNA originated in replication, not translation.. Proceedings of the National Academy of Sciences of the United States of America. 91(15):6729-34.

Hengstschläger M, Williams M, Maizels N. 1994. 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.

Weiner AM, Maizels N. 1994. Molecular evolution. Unlocking the secrets of retroviral evolution.. Current biology : CB. 4(6):560-3.

Brys A, Maizels N. 1994. LR1 regulates c-myc transcription in B-cell lymphomas.. Proceedings of the National Academy of Sciences of the United States of America. 91(11):4915-9.

Leung H, Maizels N. 1994. Regulation and targeting of recombination in extrachromosomal substrates carrying immunoglobulin switch region sequences.. Molecular and cellular biology. 14(2):1450-8.

1993

Maizels N. 1993. 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.

Williams M, Hanakahi LA, Maizels N. 1993. Purification and properties of LR1, an inducible DNA binding protein from mammalian B lymphocytes.. The Journal of biological chemistry. 268(18):13731-7.

1992

David V, Folk NL, Maizels N. 1992. Germ line variable regions that match hypermutated sequences in genes encoding murine anti-hapten antibodies.. Genetics. 132(3):799-811.

Williams M, Brys A, Weiner AM, Maizels N. 1992. 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.

Leung H, Maizels N. 1992. Transcriptional regulatory elements stimulate recombination in extrachromosomal substrates carrying immunoglobulin switch-region sequences.. Proceedings of the National Academy of Sciences of the United States of America. 89(9):4154-8.

1991

Williams M, Maizels N. 1991. LR1, a lipopolysaccharide-responsive factor with binding sites in the immunoglobulin switch regions and heavy-chain enhancer.. Genes & development. 5(12A):2353-61.

1990

Weiner AM, Maizels N. 1990. RNA editing: guided but not templated? Cell. 61(6):917-20.

Maizels N. 1990. To understand function, study structure.. Cell. 60(6):887-9.

1989

David V, Maizels N. 1989. Templated, targeted sequence diversification displays a similar choreography in different organisms.. Cold Spring Harbor symposia on quantitative biology. 54 Pt 1:227-31.

Maizels N. 1989. Might gene conversion be the mechanism of somatic hypermutation of mammalian immunoglobulin genes? Trends in genetics : TIG. 5(1):4-8.

1988

Maizels N, Lau JC, Blier PR, Bothwell A. 1988. The T-cell independent antigen, NP-ficoll, primes for a high affinity IgM anti-NP response.. Molecular immunology. 25(12):1277-82.

Maizels N, Weiner A. 1988. RNA editing. In search of a template.. Nature. 334(6182):469-70.

1987

Maizels N, Weiner AM. 1987. The 'last ribo-organism' was no breakthrough.. Nature. 330(6149):616.

Weiner AM, Maizels N. 1987. tRNA-like structures tag the 3' ends of genomic RNA molecules for replication: implications for the origin of protein synthesis.. Proceedings of the National Academy of Sciences of the United States of America. 84(21):7383-7.

Maizels N. 1987. Diversity achieved by diverse mechanisms: gene conversion in developing B cells of the chicken.. Cell. 48(3):359-60.

Maizels N, Weiner AM. 1987. Peptide-specific ribosomes, genomic tags, and the origin of the genetic code.. Cold Spring Harbor symposia on quantitative biology. 52:743-9.

1985

Maizels N, Bothwell A. 1985. The T-cell-independent immune response to the hapten NP uses a large repertoire of heavy chain genes.. Cell. 43(3 Pt 2):715-20.

Maizels N. 1985. Self-envy, the womb and the nature of goodness. A reappraisal of the death instinct.. The International journal of psycho-analysis. 66 ( Pt 2):185-92.

1974

Maizels N. 1974. E. coli lactose operon ribosome binding site.. Nature. 249(458):647-9.

Gilbert W, Maizels N, Maxam A. 1974. Sequences of controlling regions of the lactose operon.. Cold Spring Harbor symposia on quantitative biology. 38:845-55.

1973

Maizels NM. 1973. The nucleotide sequence of the lactose messenger ribonucleic acid transcribed from the UV5 promoter mutant of Escherichia coli.. Proceedings of the National Academy of Sciences of the United States of America. 70(12):3585-9.