Professor/Head of Department:

Wieringa Bé (Berend)
Ph.D/Professor. July 10, 1951.
Duties: 0.9 research, 0.1 teaching

Tel. +31.24.3614329/3614287 Fax. +31.24.3540525
E-mail b.wieringa@ncmls.ru.nl
Bé Wieringa's background is in biochemistry, molecular biology and (human)genetics. During the last decade his group has been involved in the study of the molecular pathology of Myotonic Dystrophy (DM, one of the trinucleotide repeat expansion disorders; pict1.tif) using DNA and RNA profiling technology or transgenic-knockout mouse and cell models for the study of (CTG)n repeat behaviour and gene products from the DM locus. In another line of research Wieringa's group is studying the biological significance of the Creatine(CK) - and Adenylate (AK) Kinase circuits for transfer of cellular energy (~P). Physiological properties, cytoarchitectural adaptations and rewiring of metabolic pathways in mutant (pict2.tif) muscle and brain cells in vivo and vitro are studied to better understand how the energy-metabolic state connects to cellular programming (ion-homeostasis, contractility, synaptic activity, proteome build-up).
  • Wanschers, B., van de Vorstenbosch, R., Schlager, M.A., Splinter, D., Akhmanova, A., Hoogenraad, C., Wieringa, B. and Fransen, J. (2007) A role for the Rab6B Bicaudal-D1 interaction in retrograde transport in neuronal cells. Exp. Cell Res. In Press.
  • Renema W.K., Kan, H.E., Wieringa, B. and Heerschap, A. (2007) In vivo magnetic resonance spectroscopy of transgenic mouse models with altered high-energy phosphoryl transfer metabolism. NMR Biomed. 20, 448-467.
  • Willemse M., Janssen, E., de Lange, F., Wieringa, B. and Fransen, J. (2007) ATP and FRET--a cautionary note. Nat. Biotechnol. 25, 170-172.
  • Wansink, D.G., van Herpen, R.E.M.A. and Wieringa, B. Normal and Pathophysiological Significance of Myotonic Dystrophy Protein Kinase. Genetic Instabilities and Neurological Diseases Chapter 5, 79-97. Acad. Press R.D. Wells & Ashizawa T.eds.
  • Van Herpen, R.E., Tjeertes, J.V., Mulders, S.A., Oude Ophuis, R.J., Wieringa, B. and Wansink, D.G. (2006) Coiled-coil interactions modulate multimerization, mitochondrial binding and kinase activity of myotonic dystrophy protein kinase splice isoforms. FEBS J. 273, 1124-1136.
  • van den Broek, W.J., Nelen, M.R., van der Heijden, G.W., Wansink, D.G. and Wieringa, B. (2006) Fen 1 does not control somatic hypermutability of the (CTG)(n)*(CAG)(n) repeat in a knock-in mouse model for DM1. FEBS Lett. 580, 5208-5214.
  • Klivenyi, P., Calingasan, N.Y., Starkov, A., Stavrovskaya, I.G., Kristal, B.S., Yang, L, Wieringa, B. and Beal M.F. (2005) Neuroprotective mechanisms of creatine occur in the absence of mitochondrial creatine kinase. Neurobiol. Dis. 15, 610-617.
  • van Herpen, R.E., Oude Ophuis, R.J., Wijers, M., Bennink, M.B., van de Loo, F.A., Fransen, J., Wieringa, B. and Wansink, D.G. (2005) Divergent mitochondrial and endoplasmic reticulum association of DMPK splice isoforms depends on unique sequence arrangements in tail anchors. Mol. Cell. Biol. 25, 1402-1414.
  • Streijger, F., Oerlemans, F., Ellenbroek, B.A., Jost, C.R., Wieringa, B. and Van der Zee, C.E. (2005) Structural and behavioural consequences of double deficiency for creatine kinases BCK and UbCKmit. Behav. Brain Res. 157, 219-234.
  • Dzeja, P.P., Terzic A. and Wieringa, B. (2004) Phosphotransfer dynamics in skeletal muscle from Creatine kinase gene-deleted mice. Mol.Cell.Biochem. 256, 13-27.
  • Streijger F., Jost, C.R., Oerlemans, F., Ellenbroek, B. A., Cools, A.R., Wieringa, B. and Van der Zee, I. (2004) Mice lacking the UbCKmit isoform of creatine kinase reveal slower spatial learning acquisition, diminished exploration and habituation, and reduced acoustic startle reflex responses. . Mol.Cell.Biochem. 256, 305-318.
  • Janssen E., Kuiper, J., Hodgson, D., Zingman, L.V., Alekseev, A.E., Terzic, A. and Wieringa, B. (2004) Two structurally distinct and spatially compartmentalized Adenylate kinases are expressed from the AK1 gene in mouse brain. Mol.Cell.Biochem. 256, 59-72.
  • De Bruin W, Oerlemans F and Wieringa B. (2004) Adenylate kinase I does not affect cellular growth characteristics under normal and metabolic stress conditions. Exp. Cell. Res. 297, 97-107.
  • La Spada A, Richards R.I, and Wieringa B. (2004) Dynamic mutations on the move in Banff. Nature Genet. 36, 667-670.
  • In 't Zandt H., J., A., Renema W., K.J., Streijger, F., Jost, C., Klomp, D.W.J., Oerlemans, F., van der Zee, C.E.E.M., Wieringa, B. and Heerschap, A. (2004) Cerebral Creatine kinase deficiency influences metabolite levels and morphology in the mouse brain: A quantitative in vivo 1H and 31P magnetic resonance study. J. Neurochem. 90, 1321-1330.
  • O'Cochlain, D.F., Perez-Terzic, C., Reyes, S., Kane, G.C., Behfar, A, Hodgson, D.M., Strommen, J.A., Liu, X-K, Van den Broek, W., Wansink, D.G., Wieringa, B. and Terzic, A. (2004) Transgenic Overexpression of Human DMPK Accumulates into Hypertrophic Cardiomyopathy, Myotonic Myopathy and Hypotension Traits of Myotonic Dystrophy. Hum.Mol.Genet. 13, 2505-2518.
  • Wansink, D.G., Peters, W., Schaafsma, I., Sutmuller, R.P.M., Oerlemans, F., Adema, G.J., Wieringa, B., Van der Zee, C.E.E.M., Hendriks, W.J.A.J. (2004) Mild impairment of motor nerve repair in mice lacking PTP-BL tyrosine phosphatase activity. Physiol. Genom., 19, 50-60.
  • Janssen E., de Groof A, Wijers M, Fransen J, Dzeja P.P., Terzic A. and Wieringa, B. (2003). Adenylate kinase I deficiency induces molecular and structural adaptations to support muscle energy metabolism. J Biol Chem 278,12937-12945.
  • Westerlaken, J.H., Van der Zee, C.E., Peters, W. and Wieringa, B. (2003) The DMWD protein from the myotonic dystrophy (DM1) gene region is developmentally regulated and is present most prominently in synapse-dense brain areas. Brain Res 971,116-127.
  • In 't Zandt H.J.A., de Groof A.J.C., Renema W.K.J., Oerlemans F.T.J.J., Klomp, D.W.J., Wieringa B. and Heerschap A. (2003) Presence of (phospho)Creatine in developing and adult skeletal muscle of mice without mitochondrial and cytosolic muscle Creatine kinase isoforms. J Physiol 548,847-858.
  • De Groof, A. J.C. , Fransen, J.A.M., Errington, R.J., Willems, P.H.G.M., Wieringa, B. and Koopman, W.J.H. (2002) The creatine kinase sysem is essential for optimal refill of the sarcoplasmatic reticulum Ca2+ store in skeletal muscle. J Biol Chem 277,5275-5284.
  • Jost, C., van der Zee, C.E.E.M., in 't Zandt, H.J.A., Oerlemans, F., Verheij, M., Streijger, F., Fransen, J., van Deursen, J., Heerschap, A., Cools, A. and Wieringa, B. (2002). Deficiency in the creatine kinase driven energy network in brain causes impaired learning acquisition and habituation and exacerbates age-related cognitive defects in mice. Eur J Neurosci 15,1692-1706.
  • Van den Broek, W., Nelen, M.R., Wansink, D.G., Coerwinkel, M., te Riele, H., Groenen, P. J. T. A. and Wieringa, B. (2002). Somatic expansion behavior of the (CTG)n-repeat in Myotonic Dystrophy knock-in mice is differentially affected by Msh3 and Msh6 mismatch-repair proteins. Hum Mol Genet 11,191-198.
  • Janssen, E., Dzeja, P.P., Oerlemans, F., Simonetti, A.W., Heerschap, A., de Haan, A., Rush, P.S., Terjung, R.R., Wieringa, B.and Terzic, A. (2000). Adenylate kinase 1 gene deletion disrupts muscle energetic economy despite metabolic rearrangement. EMBO J 19,6371-6381.
  • Groenen, P.J.T.A., Wansink, D.G., Coerwinkel, M., van den Broek, W., Jansen, G. and Wieringa, B. (2000). Constitutive and regulated modes of splicing produce six major myotonic dystrophy protein kinase (DMPK) isoforms with distinct properties. Hum Molec Genet 9,605-616.
  • Groenen, P.J.T.A., and Wieringa, B. (1998). Expanding complexity in myotonic dystrophy. BioEssays 20,901-912.
  • Steeghs, K., Benders, A., Oerlemans, F., de Haan, A., Heerschap, A., Ruitenbeek, W., Jost, C., van Deursen, J., Perryman, B., Pette, D., Brückwilder, M., Koudijs, J., Jap, P., Veerkamp, J. and Wieringa. B. (1997). Altered Ca2+ responses in muscles with combined mitochondrial and cytosolic creatine kinase deficiencies. Cell 89,93-103.
  • Jansen, G., Groenen, PJTA., Bachner, D., Jap, PHK, Coerwinkel, M., Oerlemans, F., Van den Broek, W., Gohlsch, B., Pette, D., Plomp, JJ., Molenaar, PC, Nederhoff, MGJ, van Echteld, CJA, Dekker, M, Berns, A., Hameister, H. and Wieringa, B. (1996). Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice. Nature Genet 13,316-324.
  • Deursen, J. van, Heerschap, A., Oerlemans, F., Ruitenbeek, W., Jap, P., Laak, H. ter, and Wieringa, B. (1993). Skeletal Muscles of Mice Deficient in Muscle Creatine Kinase Lack Burst Activity. Cell 74,621-631.
  • Jansen, G., Mahadevan, M., Amemiya, C., Wormskamp, N., Segers, B., Hendriks, W., O'Hoy, K., Baird, S., Sabourin, L., Lennon, G., Jap, P., Iles, D., Coerwinkel-Driessen, M., Hofker, M., Carrano, A.V., de Jong, P., Korneluk, R.G. and Wieringa, B. (1992). Characterisation of the myotonic dystrophy (DM) region predicts multiple protein isoform-encoding mRNAs. Nature Genet 1,261-266.
  • NWO-ZONMw Program 1999-2004: Exploring the metabolic and genetic control of compartmentalized high-energy phosphoryl transfer (P.I. B.Wieringa; 1 post-doc; 2 Ph.D. students; UMC-KUN #95250 ).
  • KWF-NKB 1998-2002: Crossroads of cellular energy and ion homeostasis: Possible targets for cancer therapy via apoptosis induction (P.I. B.Wieringa; 1 post-doc; 1 technician; UMC-KUN # 95179).
  • KWF-NKB 1999-2003: Trinucleotide repeat expansion and human cancer: The role of MSH3 and FEN-1 in unpaired DNA processing. (P.I.s B.Wieringa, H.te Riele, J. Hoeijmakers; 1 post-doc; 1 technician; UMC-KUN #95207).
  • KWF-NKB 2000-2004: Genetic networks underlying the development of human soft tissue sarcomas and leukemias (P.I s A.Geurts van Kessel, H.B. Beverloo, B. Wieringa; 1 post-doc; 1 technician).
  • KWF-NKB 2002-2006: Micro-compartmentation of nucleoside di- and triphosphate pools: Role of phosphotransfer enzymes in cell motility and metastasis (P.I. B. Wieringa; 1 post-doc; 1 technician; UMC-KUN # Pending)
  • Prinses Beatrix Fonds 2001-2003: Disturbed subcellular distribution of Myotonic Dystrophy Protein Kinase isoforms as cause of Myotonic Dystrophy (P.I. B.Wieringa; 1 post-doc; UMC-KUN #95378).
  • MDA 1999-2002: Molecular causes and consequences of CTG-repeat expansion in myotonic dystrophy (DM). (P.I. B.Wieringa; 50% post-doc; 50% technician; UMC-KUN #95273).
  • AFM 2002-2005: CTG-repeat instability in myotonic dystrophy: Understanding the mechanism(s) of expansion as a route towards therapy. (P.I's. G.Gourdon, D.Monckton, H.te Riele, B.Wieringa; 4 post-docs; UMC-KUN #95421).
  • UMC 2000-2004: Subcellular distribution of DMPK isoforms. (P.I. B.Wieringa; 1 Ph.D. student; UMC-KUN #90893).
  • UMC 2002-2006: The phosphocreatine-creatine kinase cellular energy circuit and the regulation of brown and white adipose tissue metabolism (P.I. B.Wieringa; 1 Ph.D. student; UMC-KUN #90946).