JoAnn Sekiguchi, Ph.D.

JoAnn Sekiguchi, Ph.D.

Associate Professor of Human Genetics
Associate Professor of Internal Medicine

2063 BSRB
109 Zina Pitcher Place
Ann Arbor
MI
48109-2200
Phone: 
734-764-9514
Fax: 
734-763-2162
Email: 
sekiguch@umich.edu
Staff Support: 
Sherry Taylor
Research Interests: 

Our lab studies mechanisms of DNA repair and with a focus on elucidating how specific defects in repair processes can lead to human disease outcomes, including cancer predisposition, immune system defects and fibrotic disease. We study the genes and pathways that repair DNA double strand breaks and replication associated DNA damage using a combination of molecular, biochemical, cellular and genetic approaches. Projects in the lab include (1) examination of DNA double strand break repair gene mutations associated with human immunodeficiencies and cancer; (2) characterization of the SNM1B DNA nuclease that functions in resolution of replication stress within the Fanconi anemia pathway and (3) molecular characterization of the molecular mechanisms underlying cancer and pulmonary disease in the inherited genome instability disorder, ataxia telangiectasia.

Honors and Awards: 
Mar., 2004 Pew Scholar in Biomedical Sciences, Pew Charitable Trust Foundation
Sept., 2003 Biomedical Sciences Scholar Award, University of Michigan
Dec., 2002 Ranadive Endowment Award, Leukemia and Lymphoma Society
June, 1999 Richard D. Frisbee III Foundation Fellow, Leukemia and Lymphoma Society
June, 1998 Young Investigator Award; FASEB Summer Conference-Nucleic Acid Enzymes
May, 1995 Frank Lappin Horsfall, Jr. Fellowship; Sloan-Kettering Institute
Education: 
1996 Cornell University Graduate School of Medical Sciences, Ph.D. Molecular Biology
1987 University of California, Davis, B.S. Biochemistry
1987 University of California, Davis, B.A., Psychology
Selected Publications: 

Mason JM*, Das I*, Arlt M, Kraftson S, Patel N, Glover TW and JM Sekiguchi (2013) The SNM1B/Apollo DNA nuclease prevents common fragile site instability in response to replication stress. Hum Mol Gen, In press. PMID: 23863462

Xiao H, Yu Z, Wu Y, Nan J, Merry DE, Sekiguchi JM, Ferguson DO, Lieberman AP and G Dressler (2012) A polyglutamine expansion disease protein sequesters PTIP to attenuate DNA repair and increase genomic instability. Hum Mol Gen 21:4225-4236. PMCID: PMC3441122

Chakti M, Airik R, Ghosh, A, Giles R, Chen R, Slaats G, Wang H, Hurd T, Zhou W, Cluckey A, Gee HY, Ramaswami G, Hong C, Hamilton B, Cervenka I, Ganji R, Bryja V, Arts H, van Reeuwijk J, Oud M, Letteboer S, Roepman R, Husson H, Ibraghimov-Beskrovnaya O, Ysunaga T, Walz G, Eley L, Sayer J, Schermer B, Liebau M, Benzing T, Le Corre S, Drummond I, Joles JA, Janssen S, Allen S, Natarajan S, O'Toole J, Attanasio M, Saunier S, Antignac C, Koenekoop R, Ren H, Lopez I, Nayir A, Stoetzel C, Dollfus H, Massoudi R, Gleeson J, Andreoli S, Doherty D, Lindstrad A, Golzio C, Katsanis N, Pape L, Abboud EB, Al-Rajih AA, Lewis, R, Lupski J, Goldschmeding R, Omran H, Lee E, Wang S, Sekiguchi JM, Saunders R, Johnson C, Garner E, Anderson J, Shlomai J, Nurnberg G, Nurnberg P, Levy S, Smogorzewska A, Otto E, and Friedhelm Hildebrandt (2012) Exome capture reveals ZNF423 and CEP164 mutations, linking renal cilitopathies to DNA damage response signaling. Cell 150:533-548. PMCID:PMC3433835

Mason JM and JM Sekiguchi (2011) Snm1B/Apollo functions in the Fanconi anemia pathway in response to DNA interstrand crosslinks. Hum Mol Gen, 13:2549-2559.

Jacobs C, Huang Y, Masud T, Lu W, Westfield G, Giblin W and JM Sekiguchi (2011) A hypomorphic Artemis mutation leads to aberrant chromosomal rearrangements and tumorigenesis. Hum Mol Gen, 20:806-819.

Walter JE, Rucci F, Detre C, Patrizi L, Paganini T, Recher M, Keszei M, Pessach I, Lang PA, Regenass S, Giliani S, Andersson E, Sekiguchi J, Al-Herz W, Cowan MJ, Dbaibo G, ElGhazali G, Gennery AR, Pasic S, Puck JM, Malech H, DeRavin SS, Niehues T, Schuetz C, Bleesing J, Terhorst C, Alt F W and L D Notarangelo (2010) Defects of B-cell tolerance and expansion of immunoglobulin-secreting cells in RAG-dependent immunodeficiency. J Exp Med, 207:1541-1554.

Dinkelmann, M, Spehalski, E, Stoneham, T, Buis, J, Wu, Y, Sekiguchi, JM and DO Ferguson (2009) Multiple functions of MRN in end-joining pathways during isotype class switching. Nat Struc Mol Biol, 8:808-813.

Giblin W, Chatterji M, Westfield G, Theisen B, Cheng HL, DeVido J, Alt FW, Ferguson DO, Schatz DG and JM Sekiguchi (2009) Leaky SCID and aberrant DNA rearrangements due to a hypomorphic RAG1 mutation. Blood, 113:2965-2975.

Huang Y, Giblin W, Kubec M, Westfield G, St Charles J, Chadde L, Kraftson S and JM Sekiguchi (2009) Impact of a hypomorphic Artemis disease allele on lymphocyte development, DNA end processing and genome stability. J Exp Med, 206:893-908.

Wu PY, Frit P, Meesala S, Dauvillier S, Modesti M, Andres SN, Huang Y, Sekiguchi J, Calsou P, Salles B, and MS Junop (2009) Structural and functional interaction between the human DNA repair proteins DNA Ligase IV and XRCC4. Mol Cell Biol, 29:3163-3172.

Zha S, Sekiguchi J, Brush JW, Bassing CH, and FW Alt (2008) Complementary functions of ATM and H2AX in development and suppression of genomic instability. Proc Natl Acad Sci, USA, 105:9302-9206.

Morrish TA, Garcia-Perez JL, Stamato TD, Taccioli GE, Sekiguchi J and JV Moran (2007) Endonuclease-independent LINE-1 retrotransposition at mammalian telomeres. Nature, 446:208-212.

Sekiguchi, J. M. and D. O. Ferguson (2006) DNA double-strand break repair: A relentless hunt uncovers new prey. Cell, 124:11-12.

Rooney, S., Alt, F. W., Sekiguchi, J. and J. P. Manis (2005) Artemis-independent functions of DNA-dependent protein kinase in IgH class switch recombination and development. Proc Natl Acad Sci, USA. 102:2471-2475.

Rooney, S., Sekiguchi, J., Whitlow, S., Eckersdorff, M., Manis, J. P., Lee, C., Ferguson, D. O., and F. W. Alt (2004) Artemis and p53 cooperate to suppress oncogenic N-myc amplification in progenitor B cells. Proc. Natl. Acad. Sci., USA. 101:2410-2415.

Sekiguchi, J., Alt, F. W., and M. A. Oettinger (2003) The mechanism of V(D)J recombination. pp. 57-78. In Molecular Biology of B cells, ed. Alt F. W. and T. Honjo, Elsevier Science, USA.

Dudley, D. D., Sekiguchi, J., Zhu, C., Sadofsky, M. J., Whitlow, S., DeVido, J., Monroe, R. J., Bassing, C. H. and F. W. Alt (2003) Impaired V(D)J recombination and lymphocyte development in core RAG1-expressing mice. J. Exp. Med., 198:1439-1450.

Rooney, S., Alt, F. W., Lombard, D., Whitlow, S., Eckersdorff, M., Fleming, J., Fugmann, S., Ferguson, D. O., Schatz, D. and J. Sekiguchi (2003) Defective DNA repair and increased genomic instability in Artemis-deficient murine cells. J. Exp. Med, 197:553-565.