Torik Ayoubi

Torik Ayoubi

Ph.D.

Professor and Course Director, Systems & Disease, Physiology, Foundations of Clinical Medicine

Biography:

Courses: HHP, S&D1, S&D2, S&D4, FOCM

Dr. Ayoubi obtained his PhD in 1991 at the Department of Experimental Physiology of the University of Nijmegen (The Netherlands). During that period he pioneered the use of molecular biological technologies in the neuroendocrine field and authored one of the first papers in which non-radioactive mRNA in situ hybridization was applied.

After his PhD 
work he obtained an EMBO Postdoctoral Research Fellowship at the Center for Human Genetics of the University of Leuven in Belgium to work on the regulation of the expression of the furin gene family, the long-sought pro-protein-converting enzymes that cleave proteins at pairs of basic amino acids. During his EMBO fellowship Dr. Ayoubi gathered extensive research experience and scientific knowledge in the area of regulation of gene expression.

After his EMBO fellowship, Dr. Ayoubi obtained an IWT fellowship that allowed him to apply the basic science knowledge gathered in Leuven in order to develop a set of CHO-derived cell lines that overproduce 
furin co-expressed with many different biotechnological relevant proteins. Mammalian cell lines overproducing the pro-protein processing enzyme furin laid the foundation for the development of BeneFIX® (Recombinant) Coagulation Factor IX by biotechnology companies.

As a Group Leader at the Department of Human Genetics of the University of Leuven, Dr. Ayoubi's research centered on the regulation of gene expression, and he gained an extensive knowledge of bioinformatic tools to analyze genome-wide gene expression. He then joined the Flanders Institute for Biotechnology (VIB) as a science advisor, contributing to developing strategies and tools to create an internationally renowned research structure.

Dr. Ayoubi then joined the Maastricht University Department of Clinical Genomics to focus on genome-wide gene 
analysis, and led the Transcriptomics Unit of The Genome Center. During this period he developed TCLASS
®, a proprietary, very powerful molecular multi-class tumor classifier which makes it possible to help diagnose cancers of unknown primary origin.

With the acquired expertise Dr. Ayoubi returned to the VIB to head the VIB Microarray facility which provided a fee-for-service for a wide range of scientists interested in genome-wide genome studies. Dr. Ayoubi returned to the Dutch Caribbean (where he was born on the island of Curaçao) and has been teaching Systems and Disease at SUSOM since 2016.
 
  • Cellular Physiology
  • Endocrinology
  • Pathophysiology
  • Histology
  • Genome-Wide Gene Expression Analysis
  • Functional Genomics
  • Molecular Diagnostics
  • Cancer Biomarkers
 
  • Unilever Research Prize
  • EMBO fellowship
  • IWT fellowship
  • Van Duijnhoven, J.L.P., Ayoubi, T.A.Y., Timmer, E.D.J., Braks, A.A.M., Roebroek, A.J.M., Martens, G.J.M. and Van de Ven, W.J.M. Development of a monoclonal antibody against recombinant neuroendocrine 7B2 protein. FEBS Lett., 255: 372-376, 1989.  
  • Martens, G.J.M., Bussemakers, M.J.G., Ayoubi, T.A.Y., Jenks, B.G. The novel pituitary polypeptide 7B2 is a highly-conserved protein coexpressed with proopiomelanocortin. Eur. J. Biochem. 181: 75-79, 1989. 
  • Ayoubi, T.A.Y., van Duijnhoven, J.L.P., van de Ven, W.J.M., Jenks, B.G., Roubos, E.W., and Martens, G.J.M. The neuroendocrine polypeptide 7B2 is a precursor protein. J. Biol. Chem. 265: 15644-15647, 1990. 
  • Ayoubi, T.A.Y., van Duijnhoven, H.L.P., Coenen, A.J.M., Jenks, B.G., Roubos, E.W., Martens G.J.M. Coordinated expression of 7B2 and  aMSH in the melanotrope cells of Xenopus leavis. Cell Tissue Res. 264: 329-334, 1991. 
  • Ayoubi, T.A.Y., de Kleijn, D.P.V., Roubos, E.W., Martens, G.J.M. A method for the analysis of newly synthesized mRNA. Nucleic Acids Res., 19: 3751, 1991. 
  • Van Duijnhoven, J.L.P., Verschuren, M.C.M., Timmer, E.D.J., Vissers, P.M.A.M., Groeneveld, A., Ayoubi, T.A.Y., Van den Ouweland, A.M.W. and Van de Ven, W.J.M. Application of recombinant DNA technology in epitope mapping and targeting: Development and characterization of a panel of monoclonal antibodies against the 7B2 neuroendocrine protein. J. Immunol. Methods 142: 187-189, 1991. 
  • Ayoubi, T.A.Y. Expression of proopiomelanocortin and 7B2 genes in the pituitary gland of Xenopus laevis. PhD Thesis, (1991). 
  • Ayoubi, T.A.Y., Jenks, B.G., Roubos, E.W., and Martens, G.J.M. Transcriptional and posttranscriptional regulation of the proopiomelanocortin gene in the pars intermedia of  the pituitary gland of Xenopus laevis. Endocrinology, 130: 3560-3566, 1992.  
  • Heideveld, M., Ayoubi, T.A.Y., van de Wiel, M.H.J., Martens, G.J.M., Durston, A.J. Proopiomelanocortin gene expression as a neural marker during the embryonic development of Xenopus laevis. Differentiation, 52: 195-200, 1993. 
  • Creemers, J.W.M., Siezen, R.J., Roebroek, A.J.M., Ayoubi, T.A.Y., Huylebroeck, D., G. and Van de Ven, W.J.M. Modulation of furin-mediated proprotein processing activity by site-directed mutagenesis. J. Biol. Chem. 268: 21826-21834, 1993. 
  • Ayoubi, T.A.Y., Creemers, J.W.M., Roebroek, A.J.M. and Van de Ven, W.J.M. Expression of the dibasic proprotein processing enzyme furin is directed by multiple promoters. J. Biol. Chem., 269: 9298-9303, 1994. 
  • Roebroek, A.J.M., Creemers, J.W.M., Ayoubi, T.A.Y., and Van de Ven, W.J.M. Furin-mediated proprotein processing activity: involvement of negatively charged amino acid residues in the substrate binding region. Biochimie, 76: 210-216, 1994. 
  • Creemers, J.W.M., Vey, M., Schäfer, W., Ayoubi, T.A.Y., Roebroek, A.J.M. Klenk, H.-D., Garten, W., and Van de Ven, W.J.M. Endoproteolytic cleavage of its propeptide is a prerequisite for efficient transport of furin out of the endoplasmic reticulum. J. Biol. Chem. 270: 2695-2702, 1995. 
  • Ayoubi, T.A.Y., and Van de Ven, W.J.M. A nonradioactive method to determine levels of in vitro transcription in nuclear extracts. Anal. Biochem., 225: 190-192, 1995. 
  • Roebroek, A.J.M., Ayoubi, T.A.Y., Creemers, J.W.M., Pauli, I.G.L. and Van de Ven, W.J.M. The Dfur2 gene of Drosophila melanogaster: genetic organization, expression during embryogenesis, and pro-protein processing activity of its translational product Dfurin2. DNA Cell Biol., 14: 223-234, 1995. 
  • Jansen, E., Ayoubi, T.A.Y., Meulemans, S.M.P., and Van de Ven, W.J.M. Neuroendocrine-specific expression of the human prohormone convertase 1 gene: hormonal regulation of transcription through distinct cAMP response elements. J. Biol. Chem., 270: 15391-15397, 1995. 
  • Roebroek, A.J.M., Ayoubi, T.A.Y., Van de Velde, H.J.K., Schoenmakers, E.F.P.M., Pauli, I.G.L., and Van de Ven, W.J.M. Genomic organization of the human NSP gene, prototype of a novel gene family encoding reticulons. Genomics, 32: 191-199, 1996. 
  • Ayoubi, T.A.Y., and Van de Ven, W.J.M. Regulation of gene expression by alternative promoters. FASEB J., 10: 453-460, 1996. 
  • Pittaluga, S., Ayoubi, T.A.Y., Wlodarska, I., Stul, M., Cassiman, J.J., Mecucci, C., Van den Berghe, H., Van de Ven, W.J.M., and De Wolf-Peeters C. Bcl-6 expression in reactive lymphoid tissue and in B-cell non-Hodgkin's lymphomas. J. Pathol., 179: 145-150, 1996. 
  • Ayoubi, T.A.Y., Meulemans, S.M.P., Roebroek, A.J.M., and Van de Ven, W.J.M. Production of recombinant proteins in Chinese Hamster Ovary cells overexpressing the subtilisin-like proprotein converting enzyme furin. Mol. Biol. Rep., 23: 87-95, 1996. 
  • Jansen, E., Ayoubi, T.A.Y., Meulemans, S.M.P. and Van de Ven W.J.M.  Cell type-specific protein-DNA interactions at the cAMP response elements of the prohormone convertase 1 promotor: Evidence for additional transactivators distinct from CREB/ATF family members. J. Biol. Chem., 272: 2500-2508, 1997. 
  • Jansen, E., Ayoubi, T.A.Y., Meulemans, S.M.P., and Van de Ven, W.J.M. Regulation of human prohormone convertase 2 promoter activity by the transcription factor  EGR-1.  Biochem. J., 328: 69-74, 1997. 
  • Van Rompaey, L., Ayoubi, T.A.Y.., Van de Ven, W.J.M. and Marynen, P.  Inhibition of intracellular proteolytic processing of soluble proproteins by an engineered a2-macroglobulin containing a furin recognition sequence in the bait region.  Biochem. J., 326: 507-514, 1997. 
  • Ruyter-Spira, C.P., Herbergs, J., Limpens, E., Marsh, J.A., van der Poel, J.J., Ayoubi, T.A.Y., Groenen M.A. Nucleotide sequence of the chicken HMGI-C cDNA and expression of the HMGI-C and IGFI genes in autosomal dwarf chicken embryos. Biochim Biophys Acta, 1399: 83-7. 1998. 
  • Jansen, E., Petit, M.R., Schoenmakers, E.F., Ayoubi, T.A.Y, Van de Ven, W.J.M. High mobility group protein HMGI-C: a molecular target in solid tumor formation. Gene Therapy and Molecular Biology. 3: 387-395. 1999.
  • Ayoubi, T.A.Y., Jansen, E., Meulemans, S.M., Van de Ven, W.J.M. Regulation of HMGIC expression: an architectural transcription factor involved in growth control and development. Oncogene, 18: 5076-87. 1999.
  • Petit, M.M., Fradelizi, J., Golsteyn, R.M., Ayoubi, T.A.Y., Menichi, B., Louvard, D., Van De Ven W.J.M., Friederich E. LPP, an actin cytoskeleton protein related to zyxin, harbors a nuclear export signal and transcriptional activation capacity. Mol Biol Cell 11: 117-29. 2000.
  • Marchal K.M., Engelen K., De Brabander J., Aerts S., De Moor, Ayoubi T.A.Y., Van Hummelen P. Comparison of different methodologies to identify differentially expressed genes in two-sample cDNA microarrays. Journal of Biological Systems, 10: 409-430. 2002.
  • Jan R. Brants J.R., Ayoubi T.A.Y., Chada K., Van de Ven W.J.M. and  Petit M.M.R., Differential regulation of the insulin-like growth factor II mRNA-binding protein genes by architectural transcription factor HMGA2,  FEBS letters, 569:277-83. 2004.
  • Petit MM, Meulemans SM, Alen P, Ayoubi TA, Jansen E, Van de Ven WJ. The tumor suppressor Scrib interacts with the zyxin-related protein LPP, which shuttles between cell adhesion sites and the nucleus. BMC Cell Biol. 13;6(1):1, 2005.
  • Bijnens AP, Lutgens E, Ayoubi T, Kuiper J, Horrevoets AJ, Daemen MJ. Genome-wide expression studies of atherosclerosis: critical issues in methodology, analysis, interpretation of transcriptomics data. Arterioscler Thromb Vasc Biol. 2006 Jun;26(6):1226-35. 
  • van den Bosch BJ, Lindsey PJ, van den Burg CM, van der Vlies SA, Lips DJ, van der Vusse GJ, Ayoubi TA, Doevendans PA, Smeets HJ. Early and transient gene expression changes in pressure overload-induced  cardiac hypertrophy in mice. Genomics. 2006 Oct;88(4):480-8.  
  • Meex SJ, van Greevenbroek MM, Ayoubi TA, Vlietinck R, van Vliet-Ostaptchouk JV, Hofker MH, Vermeulen VM, Schalkwijk CG, Feskens EJ, Boer JM, Stehouwer CD, van der Kallen CJ, de Bruin TW. ATF6 polymorphisms and haplotypes are associated with impaired glucose homeostasis and type 2 diabetes in Dutch Caucasians. J Clin Endocrinol Metab. 92: 2720-2725. 2007.
  • van Montfoort AP, Geraedts JP, Dumoulin JC, Stassen AP, Evers JL, Ayoubi TA. Differential gene expression in cumulus cells as a prognostic indicator of embryo viability: a microarray analysis. Mol Hum Reprod. 2008 Mar;14(3):157-68. 
  • van Eijsden RG, Eijssen LM, Lindsey PJ, van den Burg CM, de Wit LE, Rubio-Gozalbo ME, de Die CE, Ayoubi T, Sluiter W, de Coo IF, Smeets HJ. Termination of damaged protein repair defines the occurrence of symptoms in carriers of the m.3243A > G tRNA(Leu) mutation. J Med Genet. 2008 Aug;45(8):525-34. 
  • Smeets PJ, de Vogel-van den Bosch HM, Willemsen PH, Stassen AP, Ayoubi T, van der Vusse GJ, van Bilsen M. Transcriptomic analysis of PPARalpha-dependent alterations during cardiac hypertrophy. Physiol Genomics. 2008 Dec 12;36(1):15-23.  
  • SJR. Meex, D Weissglas-Volkov, C JH van der Kallen, D J Thuerauf, M MJ van Greevenbroek, CG Schalkwijk, CDA Stehouwer, E JM Feskens, L Heldens, TA Ayoubi, MH Hofker, BG Wouters, R Vlietinck, JS Sinsheimer, M-R Taskinen, J Kuusisto, M Laakso, T WA de Bruin, P Pajukanta, C C. Glembotski The ATF6-Met[67]Val substitution is associated with increased plasma cholesterol levels Arterioscler Thromb Vasc Biol. 2009 Sep;29(9):1322-7. Epub 2009 Aug 10. 
  • Martherus RS, Zeijlemaker VA, Ayoubi TA. Electrical stimulation of primary neonatal rat ventricular cardiomyocytes using pacemakers. Biotechniques. 2010 Jan;48(1):65-7. 
  • Martherus RS, Sluiter W, Timmer ED, VanHerle SJ, Smeets HJ, Ayoubi TA. Functional annotation of heart enriched mitochondrial genes GBAS and CHCHD10 through guilt by association. Biochem Biophys Res Commun. 2010 Nov 12;402(2):203-8. 
  • Martherus RS, Vanherle SJ, Timmer ED, Zeijlemaker VA, Broers JL, Smeets HJ, Geraedts JP, Ayoubi TA. Electrical signals affect the cardiomyocyte transcriptome independently of contraction. Physiol Genomics. 2010 Nov 29;42A(4):283-9.
  • T.A. Ayoubi, P. Lindsey, H.J.M. Smeets, A.P.M. Stassen In-silico dissection of tumours and its application in the identification of the tissue of origin of cancers of unknown primary site International Journal of Healthcare Technology and Management 2011 - Vol. 12, No.2  pp. 179 – 193.
  • Brandão RD, Veeck J, Van de Vijver KK, Lindsey P, de Vries B, van Elssen CH, Blok MJ, Keymeulen K, Ayoubi T, Smeets HJ, Tjan-Heijnen VC, Hupperets PS. A randomised controlled phase II trial of pre-operative celecoxib treatment reveals anti-tumour transcriptional response in primary breast cancer. Breast Cancer Res. 2013 Apr 8;15(2):R29. 
  • Lau P, Bossers K, Janky R, Salta E, Frigerio CS, Barbash S, Rothman R, Sierksma AS, Thathiah A, Greenberg D, Papadopoulou AS, Achsel T, Ayoubi T, Soreq H, Verhaagen J, Swaab DF, Aerts S, De Strooper B. Alteration of the microRNA network during the progression of Alzheimer's disease. EMBO Mol Med. 2013 Sep 9. doi: 10.1002/emmm.201201974. 
  • Papadopoulou AS, Serneels L, Achsel T, Mandemakers W, Callaerts-Vegh Z, Dooley J, Lau P, Ayoubi T, Radaelli E, Spinazzi M, Neumann M, Hébert SS, Silahtaroglu A, Liston A, D'Hooge R, Glatzel M, De Strooper B. Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice. Neurobiol Dis. 2015 Jan;73:275-88. doi: 10.1016/j.nbd.2014.10.006.  
  • Genome-Wide Gene Expression Analysis
  • Cancers of Unknown Primary
  • Alzheimer's Disease
 
Dr. Ayoubi  has presented numerous oral and poster presentations at many international conferences.
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