Scientific advisors

Prof. Dr. Gerard Martens, Ph.D., co-founder and Advisor


In September 1972, Gerard Martens (1954) started studying Chemistry/Biochemistry at the Catholic University of Nijmegen, The Netherlands, where he graduated in April 1979. He obtained his Ph.D. degree cum laude in Biochemical Neuroendocrinology (biosynthesis and secretion of peptide hormones) in May 1982 at the same university. With a stipend from the Netherlands Organization of Pure Scientific Research (ZWO) and a post-doctoral grant from the National Institutes of Health (NIH) he performed post-doctoral research in Molecular Neurobiology (molecular cloning and regulation of expression of neuropeptide genes and their receptors) in the lab of the late Prof. Dr. Edward Herbert (Molecular Neurobiology Section of the Department of Chemistry, University of Oregon, USA) from August 1982 to October 1984. He then obtained a C&C Huygens award (1984-1989) from the Netherlands Organization for Scientific Research (NWO) and an NWO-PIONIER award (1990-1995) to perform independent post-doctoral research on prohormone gene expression in neuroendocrine transducer cells in the departments of Molecular Biology and Animal Physiology (University of Nijmegen). In 1993, he was appointed Full Professor in Zoology/Animal Physiology and became Head of the Department of Molecular Animal Physiology (University of Nijmegen). He was Dean of the Faculty of Biology, supervisor of 25 PhD student projects and currently Principal Investigator (PI) at the Donders Center for Neuroscience (Donders Institute for Brain, Cognition and Behaviour), Affiliated PI at the Radboud Institute for Molecular Life Sciences (RIMLS) and Director of Education in Molecular Life Sciences (Faculty of Science, Radboud University, Nijmegen). Overall challenge of his current research is to map the brain from genotype to molecular pathways in neurodevelopmental trajectories to neuronal circuitry phenotypes and beyond to behavior, in particular understanding the background of neurodevelopmental disorders on the basis of (epi)genetic, environmental (early-life stress), molecular, cellular and behavioral analyses of a rat model for schizophrenia.

Key publications

(from a total of 194 publications in international scientific journals)
1. Martens, G.J.M., Jenks, B.G. and Van Overbeeke, A.P. (1981) Nα-acetylation is linked to α-MSH release from pars intermedia of the amphibian pituitary gland. Nature 294, 559-560.
2.
Martens, G.J.M. and Herbert, E. (1984) Polymorphism and absence of leu-enkephalin sequences in proenkephalin genes in Xenopus laevis. Nature 310, 251-254.
3. Martens, G.J.M., Braks, J.A.M., Eib, D.W., Zhou, Y. and Lindberg, I. (1994) The neuroendocrine polypeptide 7B2 is an endogenous inhibitor of prohormone convertase PC2. Proc. Natl. Acad. Sci. USA 91, 5784-5787.
4. Braks, J.A.M. and Martens, G.J.M. (1994) 7B2 is a neuroendocrine chaperone that transiently interacts with prohormone convertase PC2 in the secretory pathway. Cell 78, 263-273.
5. Van Leeuwen, F.W., De Kleijn, D.P.V., Van den Hurk, H.H., Neubauer, A., Sonnemans, M.A.F., Sluijs, J.A., Köycü, S., Ramdjielal, Salehi, A., Martens, G.J.M., Grosveld, F., Burbach, J.P.H. & Hol, E.M. (1998) Frameshift mutants of β-amyloid precursor protein and ubiquitin-B in Alzheimer’s and Down patients. Science 279, 242-247.
6. Tooze, S.A., Martens, G.J.M. & Huttner, W.B. (2001) Secretory granule biogenesis: rafting to the SNARE. Trends in Cell Biol. 11, 116-122.
7. Serneels, L., Dejaegere, T., Craessaerts, K., Horré, K., Jorissen, E., Tousseyn, T., Hébert, S.,  Coolen, M., Martens, G.J.M., Zwijsen, A., Annaert, W.,  Hartmann, D. & De Strooper, B. (2005) Differential contribution of the three Aph1 proteins to γ-secretase activity in vivo. Proc. Natl. Acad. Sci. USA 102, 1719-1724.
8. Coolen, M.W., Van Loo, K.M.J., Van Bakel, N.N.H.M., Pulford, D.J., Serneels, L., De Strooper, B., Ellenbroek, B.A., Cools, A.R. & Martens, G.J.M. (2005) Gene-dosage effect on γ-secretase component Aph-1b in a rat model for neurodevelopmental disorders. Neuron 45, 497-503.
9. Coolen, M.W., Van Loo, K.M.J., B., Ellenbroek, B.A., Cools, A.R. & Martens, G.J.M. (2006) Ontogenic reduction of Aph-1b mRNA and γ-secretase activity in rats with a complex neurodevelopmental phenotype. Mol. Psychiatry 11, 787-793 (with cover figure of study).
10. Strating, J.R.P.M., Van Bakel, N.H.M., Leunissen, J.A.M. and Martens, G.J.M. (2009) A comprehensive overview of the vertebrate p24 family: identification of a novel tissue-specifically expressed member. Molecular Biology and Evolution 26, 1707-1714.
11. Vallès, A., Boender, A.J., Gijsbers S., Haast, R.A.M., Martens, G.J.M* and De Weerd, P.* (2011) Genome-wide analysis of rat barrel cortex reveals time- and layer-specific mRNA expression changes related to experience-dependent plasticity. J. Neuroscience 31, 6140-6158. * equal contribution.
12. Vallès, A, Martens, G.J.M., De Weerd, P., Poelmans, G.*, and Aschrafi, A.* MicroRNA-137 regulates a glucocorticoid receptor-dependentsignaling network: implications for the etiology of schizophrenia. J. Psychiatry Neurosci 39, 312-320 (2014); * equal contribution.
13. Schubert, D., Martens, G.J.M., and  Kolk, S.M. Molecular underpinnings of prefrontal cortex development in rodents provide insights into the etiology of neurodevelopmental disorders. Molecular Psychiatry, 20: 795-809 (2015).
14. Klemann, C.J.H.M., Martens, G.J.M., Poelmans, G.*, and Visser, J.E.* (2016)  Validity of the MPTP-treated mouse as a model for Parkinson’s disease. Mol. Neurobiol. 53, 1625-1636; * equal contribution.
15. Jansen, E.J.R.*, Timal, S.*, Ryan, M.*, … , Martens, G.J.M., … , Lefeber D.J. (2016) ATP6AP1 deficiency: a novel immunodeficiency with hepatopathy, cognitive impairment and abnormal protein glycosylation. Nature Communications (in press); *equal contribution.
16. Witteveen, J.S., …, Brunner, H.G., Martens, G.J.M., Pfundt, R., Kleefstra, T.*, Kolk, S.M.* (2016) Haploinsufficiency of MECP2-interacting transcriptional co-repressor SIN3A causes mild intellectual disability by affecting the development of cortical integrity. Nature genetics (in press); *equal contribution.

 

Dr. Tracey Petryshen, Ph.D., scientific advisor

Petryshen_076_crop
Dr. Tracey Petryshen is an Associate Professor of Psychiatry at Harvard Medical School and an Associate Member of the Broad Institute of MIT and Harvard in the United States.  She obtained her Ph.D. degree in Medical Sciences (Medical Genetics) at the University of Calgary in Canada in 2001 for research on the genetic basis of dyslexia using family linkage and association methods. From 2001-2005, she carried out postdoctoral research training in psychiatric genetics with Dr. Pamela Sklar at the Broad Institute of MIT and Harvard.  During that time, her research focused on schizophrenia and bipolar disorder using genetic association and postmortem brain gene expression approaches, as well as mouse quantitative trait locus (QTL) mapping of psychiatric intermediate phenotypes. In 2005, she was appointed an Instructor of Psychiatry at Harvard Medical School and she established a research laboratory in the Center for Human Genetic Research at Massachusetts General Hospital in Boston. In 2009, she was promoted to Assistant Professor of Psychiatry and in June 2015 to Associate Professor.  From 2007-2012, Dr. Petryshen directed the Behavioral Neurogenetics Program in the Stanley Center for Psychiatric Research at the Broad Institute while also maintaining her academic laboratory at Massachusetts General Hospital.  Dr. Petryshen’s research focuses on the genetic basis and treatment of major psychiatric disorders including schizophrenia, bipolar disorder, depression, and compulsive disorders.  She is specifically interested in understanding how genetic changes perturb brain function and manifest as behavioral and cognitive abnormalities, and how these abnormalities can in turn be attenuated by clinical medications and novel small molecules targeting biochemical and epigenetic mechanisms implicated in psychiatric illness. Her laboratory utilizes human populations and animal and cellular model systems in combination with genetic association, behavioral neuroscience and pharmacology, biochemistry, and bioinformatics approaches.

Key publications

1. del Re E, Bergen SE, Mesholam-Gately RI, Niznikiewicz M, Goldstein JM, Woo TU, Shenton ME, Seidman LJ, McCarley RW, Petryshen TL. Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds. Transl Psychiatry 4:3346, 2014.
2. Schroeder FA, Lewis MC,  Fass DM, Wagner FF, Zhang Y-L, Hennig KM, Gale J, Zhao W-N, Reis S, Barker DD, Berry-Scott E, Kim SW, Clore EL, Hooker JM, Holson EB, Haggarty SJ, Petryshen TL.  A selective HDAC 1/2 inhibitor modulates chromatin and gene expression in brain and alters mouse behavior in two mood-related tests. PLOS ONE 8:e71323, 2013.
3. Leussis MP, Berry-Scott EM, Saito M, Jhuang H, de Haan G. Alkan O, Luce CJ, Madison JM, Sklar P, Serre T, Root DE, Petryshen TL. The ankyrin 3 (ANK3) bipolar disorder gene regulates psychiatric-related behaviors that are modulated by lithium and stress. Biol Psychiatry 73:683-90, 2013.
4. Pan JQ*, Lewis MC*, Ketterman JK, Clore EL, Riley M, Richards K, Berry-Scott E, Liu X, Wagner FF, Holson EB, Neve RL, Biechele TL, Moon RT, Scolnick EM, Petryshen TL, Haggarty SJ. (joint corresponding author)  AKT Kinase Activity is Required for Lithium to Modulate Mood-Related Behaviors in Mice. Neuropsychopharmacology 36:1397-411, 2011. *equal contribution
5. Petryshen TL, Sabeti PC, Aldinger KA, Fry B, Fan JB, Schaffner SF, Waggoner SG, Tahl AR, Sklar P. Population genetic study of the brain-derived neurotrophic factor (BDNF) gene. Mol Psychiatry 15:810-5, 2010.
6. Petryshen TL, Middleton FA, Kirby A, Aldinger KA, Purcell S, Tahl AR, Morley CP, McGann L,  Gentile KL, Rockwell GN, Medeiros HM, Carvalho C, Macedo A, Dourado A, Valente J, Ferreira CP, Patterson NJ, Azevedo MH, Daly MJ, Pato CN, Pato MT, Sklar P. Support for involvement of neuregulin 1 in schizophrenia pathophysiology. Mol Psychiatry 10:366-374, 2005.
7. Petryshen TL, Middleton FA, Tahl AR, Rockwell GN, Purcell S, Aldinger KA, Kirby A, Morley CP, McGann L, Gentile KL, Waggoner SG, Medeiros HM, Carvalho C, Macedo A, Albus M, Maier W, Trixler M, Eichhammer P, Schwab SG, Wildenauer DB, Azevedo MH, Pato MT, Pato CN, Daly MJ, Sklar P. Genetic investigation of chromosome 5q GABAA receptor subunit genes in schizophrenia. Mol Psychiatry 10(12):1074-1088, 2005.


Prof. Dr. Wiebe Kruijer, Ph.D., scientific advisor

wiebekruijer
Wiebe Kruijer (1951) studied Chemistry/Biochemistry and Pharmacy at the University of Groningen, The Netherlands, where he graduated in 1978. He obtained his Ph.D. degree in Physiological Chemistry (nucleotide sequence analysis of wild-type and mutant genes encoding adenovirus DNA binding protein) in 1983 at the University of Utrecht, The Netherlands.  He then worked as a (senior) Research Associate at the Molecular Biology and Virology Laboratory, The Salk Institute for Biological Studies, San Diego, USA (1983-1985) and at the Hubrecht Laboratory, Netherlands Institute of Developmental Biology (NIOB) of the Royal Academy of Arts and Sciences, Utrecht (1985-1993). From 1993 to 2006, he was Professor of Developmental Genetics at the Department of Biology, Faculty of Mathematics and Natural Sciences, University of Groningen. From 2003 until present, he was Professor and continues as Emeritus Professor in Molecular Cell Biology, Faculty of Science and Technology, University of Twente, The Netherlands.

Key publications

1. Kruijer, W., Cooper, J. A., Hunter, T. and Verma, I. M. Platelet-derived growth factor induces rapid but transient expression of the c-fos gene and protein. Nature 312, 711-716 (1984)
2. Shen, S., van der Saag, P. T. and Kruijer, W. Dominant negative retinoic acid receptor beta. Mech Dev 40, 177-189 (1993).
3. Jonk, L. J., de Jonge, M. E., Pals, C. E., Wissink, S., Vervaart, J. Schoorlemmer, J. and Kruijer, W. Cloning and expression during development of three murine members of the COUP family of nuclear orphan receptors. Mech Dev 47, 81-97 (1994).
4. Schoorlemmer, J., van Puijenbroek, A., van den Eijnden, M., Jonk, L., Pals, C . and Kruijer, W. Characterization of a negative retinoic acid response element in the murine Oct4 promoter. Mol Cell Biol 14, 1122-1136 (1994).
5. Poels, M.W.J., Golbach, L.A., Poot, A.A. ,Feijen, J. ,Grijpma, D.W. and Kruijer, W. Enhanced collagen type IV based differentiation of embryonic stem cells towards Flk-1 expressing vascular progenitors by the Wnt/β-catenin synergist QS11. J. Macromol. Symp. 209,210, 236-243 (2011).