Faculty

JoAnn Sekiguchi, Ph.D.
Associate Professor of Internal Medicine
Associate Professor of Human Genetics

sekiguch@med.umich.edu

734/764-9514

Lab address:
2063 BSRB
109 Zina Pitcher Place
Ann Arbor, MI 48109-2200

Lab website

Research summary:

Research in the Sekiguchi lab focuses on elucidating the mechanisms and regulation of DNA repair processes in mammalian cells.  The two major pathways of repair we study are DNA double strand break repair via the non-homologous end joining pathway and resolution of stalled or blocked replication forks via the Fanconi anemia pathway.  Both pathways play critical roles in preventing accumulation of unwanted DNA damage and in maintaining the integrity of the genome.  Studies in my lab take advantage of a combination of biochemical, molecular, cellular and genetic approaches to elucidate the roles of proteins in DNA repair and to determine the impact of defective repair on genome stability, immune system development, and tumorigenesis.  We have generated several novel mouse models harboring gene-targeted null, hypomorphic knock-in and conditional alleles in genes known to be mutated in human immunodeficiency and/or cancer predisposition syndromes.  Recent work has focused on identification of pathways required for repair of oncogene induced DNA damage and targeted inhibition of these pathways to selectively kill tumor cells overexpressing oncogenes.  In addition, the lab is investigating effective therapeutic strategies for treating or attenuating disease symptoms caused by DNA repair deficiencies.

Education:

INSTITUTION AND LOCATION

DEGREE
(if applicable)

Completion Date
MM/YYYY

FIELD OF STUDY

University of California, Davis; Davis, CA

B.A./B.S.

05/1987

Psychology/Biochemistry

Cornell University Graduate School of Medical Sciences; New York, NY

Ph.D.

05/1996

Molecular Biology

Sloan Kettering Institute; New York, NY

Postdoctoral

05/1997

Molecular Biology

Harvard Medical School; Boston, MA

Postdoctoral

09/2003

Immunology and Genetics

Appointments and Honors:
1995                Frank Lappin Horsfall, Jr., Fellowship, Sloan Kettering Institute
1998                Young Investigator Award; FASEB Summer Conference-Nucleic Acid Enzymes
1999                Richard D. Frisbee III Foundation Fellow, Leukemia and Lymphoma Society
2002                Ranadive Endowment Award, Leukemia and Lymphoma Society
2003                Biomedical Sciences Scholars Award, University of Michigan
2004                Pew Scholars Award in Biomedical Sciences, Pew Charitable Foundation
2006                W.M. Keck Foundation Distinguished Young Scholars Semi-finalist
2008                Elizabeth Caroline Crosby award, University of Michigan
2009-2013       Member, University of Michigan Medical School, Biomedical Research Council
2012-2017       Director, Graduate Studies; University of Michigan; Department of Human
Genetics
2013-present   Member, Molecular Genetics B Study Section - MGB
2015-present   Chair, Human Genetics Graduate Education Committee; Department of Human
Genetics
2015-present   Member, Rackham Integrity Review Board; Rackham Graduate School; Univ. of
Michigan
2016                Basic Sciences Teaching Award; Endowment for Basic Sciences; University of
Michigan Medical School
2017-present   Member, Chair’s Advisory Committee; Department of Human Genetics

Selected Publications:

Spehalski E, Capper, K, Smith CJ, Morgan MJ, Dinkelmann M, Buis J, Sekiguchi, JM^ and DO Ferguson^ (2017) MRE11 promotes tumorigenesis by facilitating resistance to oncogene-induced replication stress. Cancer Research, doi: 10.1158/0008-5472.CAN-17-1355. [Epub ahead of print]. ^co-corresponding authors

Ku CJ, Sekiguchi J, Panwar B, Guan Y, Takahashi S, Yoh K, Maillard I, Howoya T and JD Engel.  (2017) GATA3 abundance is a critical determinant of T cell receptor beta allelic exclustion.  Mol Cell Biol, 37. PMCID: PMC5452726 [Available on 2017-11-30]

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 22:4901-4913.  

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.

Mason JM and JM Sekiguchi (2011) Snm1B/Apollo functions in the Fanconi anemia pathway in response to DNA interstrand crosslinks.  Hum Mol Gen 20:2549-2559.

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.

Giblin W, Chatterji M, Westfield G, Masud T, 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.

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.

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.

Buis J, Wu Y, Deng Y, Leddon J, Westfield G, Eckersdorff M, Sekiguchi J, Chang S and D O Ferguson (2008) Mre11 nuclease activity has essential roles in DNA repair and genomic stability distinct from ATM activation.  Cell, 135:85-96.

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.