• Male

J.E.J. Guikema PhD

Position: Scientific staff member (UD)
Main activities: Research
Specialisation: Molecular biology of immunoglobulin gene recombinations
foto
Focus of research:

Our research is focused on immunoglobulin gene recombinations in B cells. We aim to understand the basic mechanisms of these recombinations, and the contribution to genomic instability in malignant leukemias and lymphomas. We are especially interested in the generation and resolution of DNA double-strand breaks during immunoglobulin gene recombinations. To that end, we use genome-wide screening approaches to detect DNA breaks in developing B cells that arise as 'collateral damage' of RAG1/2-mediated V(D)J recombinations, and in activated mature B cells during AID-dependent somatic hypermutations and class switch recombination. 

AMC themes: Oncology
Departments: Pathology
Bahjat M, Bloedjes TA, van der Veen A, de Wilde G, Maas C, Guikema JEJ, Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay. JOVE-J VIS EXP 2017;ahead of print [PubMed]
Bahjat M, Guikema JEJ, The Complex Interplay between DNA Injury and Repair in Enzymatically Induced Mutagenesis and DNA Damage in B Lymphocytes. INT J MOL SCI 2017;18 (9):1876 [PubMed]
Dzikiewicz-Krawczyk A, Kok K, Slezak-Prochazka I, Robertus JL, Bruining J, Tayari MM, Rutgers B, de Jong D, Koerts J, Seitz A, Li J, Tillema B, Guikema JE, Nolte IM, Diepstra A, Visser L, Kluiver J, van den Berg A, ZDHHC11 and ZDHHC11B are critical novel components of the oncogenic MYC-miR-150-MYB network in Burkitt lymphoma. LEUKEMIA 2017;31 (6):1470-1473 [PubMed]
Guikema JE, Amiot M, Eldering E, Exploiting the pro-apoptotic function of NOXA as a therapeutic modality in cancer. EXPERT OPIN THER TAR 2017;21 (8):767-779 [PubMed]
Reshetova P, van Schaik BDC, Klarenbeek PL, Doorenspleet ME, Esveldt REE, Tak PP, Guikema JEJ, de Vries N, van Kampen AHC, Computational Model Reveals Limited Correlation between Germinal Center B-Cell Subclone Abundancy and Affinity: Implications for Repertoire Sequencing. FRONT IMMUNOL 2017;8:221 [PubMed]
van Andel H, Ren Z, Koopmans I, Joosten SPJ, Kocemba KA, de Lau W, Kersten MJ, de Bruin AM, Guikema JEJ, Clevers H, Spaargaren M, Pals ST, Aberrantly expressed LGR4 empowers Wnt signaling in multiple myeloma by hijacking osteoblast-derived R-spondins. P NATL ACAD SCI USA 2017;114 (2):376-381 [PubMed]
Bende RJ, Janssen J, Wormhoudt TAM, Wagner K, Guikema JEJ, van Noesel CJM, Identification of a novel stereotypic IGHV4-59/IGHJ5-encoded B-cell receptor subset expressed by various B-cell lymphomas with high affinity rheumatoid factor activity. HAEMATOLOGICA 2016;101 (5):e200-e203 [PubMed]
Ochodnicka-Mackovicova K, Bahjat M, Maas C, van der Veen A, Bloedjes TA, de Bruin AM, van Andel H, Schrader CE, Hendriks RW, Verhoeyen E, Bende RJ, van Noesel CJM, Guikema JEJ, The DNA Damage Response Regulates RAG1/2 Expression in Pre-B Cells through ATM-FOXO1 Signaling. J IMMUNOL 2016;197 (7):2918-2929 [PubMed]
Slinger E, Wensveen FM, Guikema JE, Kater AP, Eldering E, Chronic lymphocytic leukemia development is accelerated in mice with deficiency of the pro-apoptotic regulator NOXA. HAEMATOLOGICA 2016;101 (9):e376-e377 [PubMed]
Slot LM, Hoogeboom R, Smit LA, Wormhoudt TAM, Biemond BJ, Oud MECM, Schilder-Tol EJM, Mulder AB, Jongejan A, van Kampen AHC, Kluin PM, Guikema JEJ, Bende RJ, van Noesel CJM, B-Lymphoblastic Lymphomas Evolving from Follicular Lymphomas Co-Express Surrogate Light Chains and Mutated Gamma Heavy Chains. AM J PATHOL 2016;186 (12):3273-3284 [PubMed]
Bende RJ, Slot LM, Hoogeboom R, Wormhoudt TAM, Adeoye AO, Guikema JEJ, van Noesel CJM, Stereotypic rheumatoid factors that are frequently expressed in mucosa-associated lymphoid tissue-type lymphomas are rare in the labial salivary glands of patients with Sjögren's syndrome. ARTHRITIS RHEUMATOL 2015;67 (4):1074-1083 [PubMed]
Hoogeboom R, Reinten RJA, Schot JJ, Guikema JEJ, Bende RJ, van Noesel CJM, In vitro induction of antibody secretion of primary B-cell chronic lymphocytic leukaemia cells. LEUKEMIA 2015;29 (1):244-247 [PubMed]
Kersten MJ, Guikema JEJ, MYC in diffuse large B-cell lymphoma: always the bad guy?. LEUKEMIA LYMPHOMA 2015;56 (11):3003-3004 [PubMed]
Ochodnicka-Mackovicova K, Bahjat M, Bloedjes TA, Maas C, de Bruin AM, Bende RJ, van Noesel CJM, Guikema JEJ, NF-κB and AKT signaling prevent DNA damage in transformed pre-B cells by suppressing RAG1/2 expression and activity. BLOOD 2015;126 (11):1324-1335 [PubMed]
Guikema JEJ, Linehan EK, Esa N, Tsuchimoto D, Nakabeppu Y, Woodland RT, Schrader CE, Apurinic/apyrimidinic endonuclease 2 regulates the expansion of germinal centers by protecting against activation-induced cytidine deaminase-independent DNA damage in B cells. J IMMUNOL 2014;193 (2):931-939 [PubMed]
Khair L, Guikema JEJ, Linehan EK, Ucher AJ, Leus NGJ, Ogilvie C, Lou Z, Schrader CE, Stavnezer J, ATM Increases Activation-Induced Cytidine Deaminase Activity at Downstream S Regions during Class-Switch Recombination. J IMMUNOL 2014;192 (10):4887-4896 [PubMed]
Hoogeboom R, van Kessel KPM, Hochstenbach F, Wormhoudt TA, Reinten RJA, Wagner K, Kater AP, Guikema JEJ, Bende RJ, van Noesel CJM, A mutated B cell chronic lymphocytic leukemia subset that recognizes and responds to fungi. J EXP MED 2013;210 (1):59-70 [PubMed]
Hoogeboom R, Wormhoudt TA, Schipperus MR, Langerak AW, Dunn-Walters DK, Guikema JEJ, Bende RJ, van Noesel CJM, A novel chronic lymphocytic leukemia subset expressing mutated IGHV3-7-encoded rheumatoid factor B-cell receptors that are functionally proficient. LEUKEMIA 2013;27 (3):738-740 [PubMed]
Lascano V, Guadagnoli M, Schot JG, Luijks DM, Guikema JEJ, Cameron K, Hahne M, Pals S, Slinger E, Kipps TJ, van Oers MHJ, Eldering E, Medema JP, Kater AP, Chronic lymphocytic leukemia disease progression is accelerated by APRIL-TACI interaction in the TCL1 transgenic mouse model. BLOOD 2013;122 (24):3960-3963 [PubMed]
Guikema JEJ, Gerstein RM, Linehan EK, Cloherty EK, Evan-Browning E, Tsuchimoto D, Nakabeppu Y, Schrader CE, Apurinic/Apyrimidinic endonuclease 2 is necessary for normal B cell development and recovery of lymphoid progenitors after chemotherapeutic challenge. J IMMUNOL 2011;186 (4):1943-1950 [PubMed]
Pei DS, Yang XJ, Liu W, Guikema JEJ, Schrader CE, Strauss PR, A novel regulatory circuit in base excision repair involving AP endonuclease 1, Creb1 and DNA polymerase beta. NUCLEIC ACIDS RES 2011;39 (8):3156-3165 [PubMed]
Staszewski O, Baker RE, Ucher AJ, Martier R, Stavnezer J, Guikema JEJ, Activation-induced cytidine deaminase induces reproducible DNA breaks at many non-Ig Loci in activated B cells. MOL CELL 2011;41 (2):232-242 [PubMed]
Guikema JEJ, Schrader CE, Brodsky MH, Linehan EK, Richards A, El Falaky N, Li DH, Sluss HK, Szomolanyi-Tsuda E, Stavnezer J, p53 represses class switch recombination to IgG2a through its antioxidant function. J IMMUNOL 2010;184 (11):6177-6187 [PubMed]
Guikema JEJ, Stavnezer J, Schrader CE, The role of Apex2 in class-switch recombination of immunoglobulin genes. INT IMMUNOL 2010;22 (3):213; author reply 213-213; author reply 214 [PubMed]
Schrader CE, Guikema JEJ, Wu X, Stavnezer J, The roles of APE1, APE2, DNA polymerase beta and mismatch repair in creating S region DNA breaks during antibody class switch. PHILOS T R SOC B 2009;364 (1517):645-652 [PubMed]
Guikema JEJ, Schrader CE, Leus NGJ, Ucher A, Linehan EK, Werling U, Edelmann W, Stavnezer J, Reassessment of the role of Mut S homolog 5 in Ig class switch recombination shows lack of involvement in cis- and trans-switching. J IMMUNOL 2008;181 (12):8450-8459 [PubMed]
Guikema JEJ, Schuuring E, Kluin PM, Structure and consequences of IGH switch breakpoints in Burkitt lymphoma. J NATL CANCER INST MONOGR 2008;39 (39):32-36 [PubMed]
Stavnezer J, Guikema JEJ, Schrader CE, Mechanism and regulation of class switch recombination. ANNU REV IMMUNOL 2008;26:261-292 [PubMed]
Guikema JEJ, Linehan EK, Tsuchimoto D, Nakabeppu Y, Strauss PR, Stavnezer J, Schrader CE, APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination. J EXP MED 2007;204 (12):3017-3026 [PubMed]
Schrader CE, Guikema JEJ, Linehan EK, Selsing E, Stavnezer J, Activation-induced cytidine deaminase-dependent DNA breaks in class switch recombination occur during G1 phase of the cell cycle and depend upon mismatch repair. J IMMUNOL 2007;179 (9):6064-6071 [PubMed]
Guikema JEJ, de Boer-Bergsma RW, Akkermans K, Schuuring E, Kluin PM, H2AX is not affected in mantle cell lymphoma with 11q23 deletion. GENE CHROMOSOME CANC 2006;45 (4):426-427 [PubMed]
Guikema JEJ, de Boer C, Haralambieva E, Smit LA, van Noesel CJM, Schuuring E, Kluin PM, IGH switch breakpoints in Burkitt lymphoma: exclusive involvement of noncanonical class switch recombination. GENE CHROMOSOME CANC 2006;45 (9):808-819 [PubMed]
Guikema JEJ, Fenton JAL, de Boer C, Kleiverda K, Brink AATP, Raap AK, Estrov Z, Schuuring E, Kluin PM, Complex biallelic IGH rearrangements in IgM-expressing Z-138 cell line: Involvement of downstream immunoglobulin class switch recombination. GENE CHROMOSOME CANC 2005;42 (2):164-169 [PubMed]
Guikema JEJ, Rosati S, Akkermans K, Bende RJ, van Noesel CJM, van Krieken JH, Hansmann ML, Schuuring E, Kluin PM, Quantitative RT-PCR analysis of activation-induced cytidine deaminase expression in tissue samples from mantle cell lymphoma and B-cell chronic lymphocytic leukemia patients. BLOOD 2005;105 (7):2997-2998 [PubMed]
Guikema JEJ, Hovenga S, Vellenga E, Bos NA, Heterogeneity in the multiple myeloma tumor clone. LEUKEMIA LYMPHOMA 2004;45 (5):857-871 [PubMed]
Guikema JEJ, Vellenga E, Abdulahad WH, Hovenga S, Bos NA, CD27-triggering on primary plasma cell leukaemia cells has anti-apoptotic effects involving mitogen activated protein kinases. BRIT J HAEMATOL 2004;124 (3):299-308 [PubMed]
Haralambieva E, Schuuring E, Rosati S, van Noesel C, Jansen P, Appel I, Guikema J, Wabinga H, Bleggi-Torres LF, Lam K, van den Berg E, Mellink C, van Zelderen-Bhola S, Kluin P, Interphase fluorescence in situ hybridization for detection of 8q24/MYC breakpoints on routine histologic sections: validation in Burkitt lymphomas from three geographic regions. GENE CHROMOSOME CANC 2004;40 (1):10-18 [PubMed]
Guikema JEJ, Hovenga S, Vellenga E, Conradie JJ, Abdulahad WH, Bekkema R, Smit JW, Zhan F, Shaughnessy J Jr, Bos NA, CD27 is heterogeneously expressed in multiple myeloma: low CD27 expression in patients with high-risk disease. BRIT J HAEMATOL 2003;121 (1):36-43 [PubMed]
Smit LA, Bende RJ, Aten J, Guikema JEJ, Aarts WM, van Noesel CJM, Expression of activation-induced cytidine deaminase is confined to B-cell non-Hodgkin's lymphomas of germinal-center phenotype. CANCER RES 2003;63 (14):3894-3898 [PubMed]
Guikema JEJ, Vellenga E, Bakkus MHC, Bos NA, Myeloma clonotypic B cells are hampered in their ability to undergo B-cell differentiation in vitro. BRIT J HAEMATOL 2002;119 (1):54-61 [PubMed]
de Bont ES, Guikema JE, Scherpen F, Meeuwsen T, Kamps WA, Vellenga E, Bos NA, Mobilized human CD34+ hematopoietic stem cells enhance tumor growth in a nonobese diabetic/severe combined immunodeficient mouse model of human non-Hodgkin's lymphoma. CANCER RES 2001;61 (20):7654-7659 [PubMed]
Hovenga S, de Wolf JT, Guikema JE, Klip H, Smit JW, Smit Sibinga CT, Bos NA, Vellenga E, Autologous stem cell transplantation in multiple myeloma after VAD and EDAP courses: a high incidence of oligoclonal serum Igs post transplantation. BONE MARROW TRANSPL 2000;25 (7):723-728 [PubMed]
Willems P, Verhagen O, Segeren C, Veenhuizen P, Guikema J, Wiemer E, Groothuis L, Jong TB, Kok H, Bloem A, Bos N, Vellenga E, Mensink E, Sonneveld P, Lokhorst H, van der Schoot E , Raymakers R, Consensus strategy to quantitate malignant cells in myeloma patients is validated in a multicenter study. Belgium-Dutch Hematology-Oncology Group. BLOOD 2000;96 (1):63-70 [PubMed]
Guikema JE, Vellenga E, Veeneman JM, Hovenga S, Bakkus MH, Klip H, Bos NA, Multiple myeloma related cells in patients undergoing autologous peripheral blood stem cell transplantation. BRIT J HAEMATOL 1999;104 (4):748-754 [PubMed]
Key publications

Hoogeboom R, van Kessel KPM, Hochstenbach F, Wormhoudt TA, Reinten RJA, Wagner K, Kater AP, Guikema JEJ, Bende RJ, van Noesel CJM, A mutated B cell chronic lymphocytic leukemia subset that recognizes and responds to fungi. J EXP MED 2013;210 (1):59-70 [PubMed]
Staszewski O, Baker RE, Ucher AJ, Martier R, Stavnezer J, Guikema JEJ, Activation-induced cytidine deaminase induces reproducible DNA breaks at many non-Ig Loci in activated B cells. MOL CELL 2011;41 (2):232-242 [PubMed]
Guikema JEJ, Gerstein RM, Linehan EK, Cloherty EK, Evan-Browning E, Tsuchimoto D, Nakabeppu Y, Schrader CE, Apurinic/Apyrimidinic endonuclease 2 is necessary for normal B cell development and recovery of lymphoid progenitors after chemotherapeutic challenge. J IMMUNOL 2011;186 (4):1943-1950 [PubMed]
Stavnezer J, Guikema JEJ, Schrader CE, Mechanism and regulation of class switch recombination. ANNU REV IMMUNOL 2008;26:261-292 [PubMed]
Guikema JEJ, Linehan EK, Tsuchimoto D, Nakabeppu Y, Strauss PR, Stavnezer J, Schrader CE, APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination. J EXP MED 2007;204 (12):3017-3026 [PubMed]


All Publications

Curriculum Vitae

 NAME
Jeroen E.J. Guikema, Ph.D.

TITLE
Assistant Professor (tenure track), AMC Fellow
Academic Medical Center, University of Amsterdam, The Netherlands

ADDRESS
Department of Pathology
Academic Medical Center, University of Amsterdam
Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
Phone: +31-20-566-5708
Fax: +31-20-566-9523
E-mail: J.E.Guikema@amc.uva.nl

EDUCATION
•2004: Ph.D. Departments of Cell Biology and Hematology, University Medical Center Groningen, University of Groningen, The Netherlands. Thesis title: ‘Heterogeneity of Clonal B cells in Multiple Myeloma’
•1998: M.Sc. Medical and Molecular Biology, University of Groningen, The Netherlands, cum laude

POSITIONS
•2010–present: Assistant Professor (tenure track), AMC Fellow
Department of Pathology, Academic Medical Center, University of Amsterdam, The Netherlands
•2005–2010: Postdoctoral Fellow with Prof. Janet Stavnezer, Department of Microbiology and Molecular Genetics, University of Massachusetts, Worcester, MA, USA
•2004–2005: Postdoctoral Fellow with Prof. Philip Kluin, Department of Pathology, University Medical Center Groningen, The Netherlands

INTERNATIONAL ACTIVITIES
•Postdoctoral fellow in the lab of Prof. Janet Stavnezer at the University of Massachusetts Medical School, Worcester, MA, USA: October 2005-March 2010.
•Rotation project in the lab of Prof. Kris Thielemans at the Free University of Brussels, Belgium, 7 months: August 1996-March 1997.

OTHER ACADEMIC ACTIVITIES
•Chairman of the ‘Malignant Lymphoma’ subcommittee of the Dutch Cancer Society (KWF).
•Member of the Dutch Hematology Congress (NVvH) program committee.
•Co-organizer of the biweekly ‘Amsterdam Immunology Meeting’ (AIM) at the Academic Medical Center, Amsterdam.
•Ad hoc reviewer for Journal of Immunology, Journal of Experimental Medicine, British Journal of Haematology, Genes Chromosomes and Cancer.

NON-ACADEMIC ACTIVITIES
•Scientific consultant and member of the scientific advisory board at ‘ImmunoQuality Therapeutics Corporation’ based in Groningen, The Netherlands.

MEMBERSHIPS
•American Association of Immunologists (AAI)
•Dutch Society for Immunology (NVVI)
•Dutch Society for Hematology (NVvH)

SCHOLARSHIPS AND PRIZES

  • 2012-2017: NWO-VIDI €800,000; 1/10/2012-31/09/2017
  • 2010-2015: Amsterdam Academic Medical Center Fellowship Award €700,000; 1/04/2010-31/3/2015
  • 2007-2009: Cancer Research Institute Award $130,500; 1/01/2007-12/31/2009

 

Research programmes

Prof. dr. C.J.M. van Noesel (B cell biology and the pathogenesis of B-NHL/ The serrated neoplasia pathway to colorectal cancer)

Other research related activities
  • Membership of advisory board / Consultant, IQ Therapeutics
Current research funding
  • AMC
  • Stichting KIKA
  • ZonMw