Function: Postdoc
Address (work):
Department of Metabolic Diseases
University Medical Center Utrecht
Room KE.03.139.2
Lundlaan 6, 3584 EA Utrecht
The Netherlands
phone: 088 - 75 543 37 (lab) / 75 552 27 (room)
e-mail:
A.Koppen@umcutrecht.nlJune 2008-current
Scientific Laboratory Assistant (Wetenschappelijk Laboratorium Medewerker)
Department of Metabolic and Endocrine Diseases, Kalkhoven Group, UMC Utrecht
February 2007-May 2008
Postdoctoral research associate
Department of Metabolic and Endocrine Diseases, Kalkhoven Group, UMC Utrecht
January 2006-January 2007
PhD student, temporarily assistant group leader
Department of Human Genetics, AMC Amsterdam
August 2001-January 2006
PhD student
Department of Human Genetics, AMC Amsterdam
Title: Gene Regulation by MYCN in Neuroblastoma
PhD awarded: March 25, 2008
Brown vs white adipocytes: the PPARgamma coregulator story.
Koppen A, Kalkhoven E.
FEBS Lett. 2010 Aug 4;584(15):3250-9. Epub 2010 Jun 30. Review.
Epidermis-type lipoxygenase 3 regulates adipocyte differentiation and peroxisome proliferator-activated receptor gamma activity.
Hallenborg P, Jørgensen C, Petersen RK, Feddersen S, Araujo P, Markt P, Langer T, Furstenberger G, Krieg P, Koppen A, Kalkhoven E, Madsen L, Kristiansen K.
Mol Cell Biol. 2010 Aug;30(16):4077-91. Epub 2010 Jun 7.
Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) but not PPARalpha serves as a plasma free fatty acid sensor in liver.
Sanderson LM, Degenhardt T, Koppen A, Kalkhoven E, Desvergne B, Müller M, Kersten S.
Mol Cell Biol. 2009 Dec;29(23):6257-67.
Nuclear receptor-coregulator interaction profiling identifies TRIP3 as a novel peroxisome proliferator-activated receptor gamma cofactor.
Koppen A, Houtman R, Pijnenburg D, Jeninga EH, Ruijtenbeek R, Kalkhoven E.
Mol Cell Proteomics. 2009 Oct;8(10):2212-26. Epub 2009 Jul 10.
Effect of synthetic dietary triglycerides: a novel research paradigm for nutrigenomics.
Sanderson LM, de Groot PJ, Hooiveld GJ, Koppen A, Kalkhoven E, Müller M, Kersten S.
PLoS One. 2008 Feb 27;3(2):e1681.
Dickkopf-3 expression is a marker for neuroblastic tumor maturation and is down-regulated by MYCN.
Koppen A, Ait-Aissa R, Koster J, Øra I, Bras J, van Sluis PG, Caron H, Versteeg R, Valentijn LJ.Int J Cancer. 2008 Apr 1;122(7):1455-64.
Direct regulation of the minichromosome maintenance complex by MYCN in neuroblastoma.
Koppen A, Ait-Aissa R, Koster J, van Sluis PG, Ora I, Caron HN, Volckmann R, Versteeg R, Valentijn LJ. Eur J Cancer. 2007 Nov;43(16):2413-22. Epub 2007 Sep 10.
Dickkopf-1 is down-regulated by MYCN and inhibits neuroblastoma cell proliferation.
Koppen A, Ait-Aissa R, Hopman S, Koster J, Haneveld F, Versteeg R, Valentijn LJ. Cancer Lett. 2007 Oct 28;256(2):218-28. Epub 2007 Jul 23.
Inhibition of a new differentiation pathway in neuroblastoma by copy number defects of N-myc, Cdc42, and nm23 genes.
Valentijn LJ, Koppen A, van Asperen R, Root HA, Haneveld F, Versteeg R. Cancer Res. 2005 Apr 15;65(8):3136-45.
Four-dimensional imaging of chromatin dynamics during the assembly of the interphase nucleus.
Manders EM, Visser AE, Koppen A, de Leeuw WC, van Liere R, Brakenhoff GJ, van Driel R. Chromosome Res. 2003;11(5):537-47.
- From 2010, Lecturer on ‘Metabolic Disorders’ for the Master’s program Biomedical Sciences
- From 2010, Lecturer on ‘Metabolism’ for the MSc program Biomedical Sciences
- From 2009, Lecturer on ‘Healthy and sick cells’ for the BSc program Medicine
- The role of the nuclear receptor PPARγ in adipogenesis
- The interaction between nuclear receptors and coregulators
At the moment, my research is focused on two subjects. The first project concerns the effect of mutations in PPARγ in patients suffering from familial partial lipodystrophy (FPLD). This disease is characterized by alterations in adipose tissue distribution, severe insulin resistance, increased risk for cardiovascular disease, high blood pressure and dyslipidemia. Several heterozygous mutations have been found in the PPARG gene in FPLD patients. PPARG encodes the Peroxisome Proliferator Activated Receptor γ, a member of the PPAR nuclear receptor family, and key regulator of adipogenesis. Nuclear receptors are transcription factors which can be activated by NR specific ligands. Endogenous ligands for PPARγ include prostaglandins and several fatty acids. During adipocyte differentiation PPARγ is expressed, activated and in turn induces the expression of a large set of genes important for adipogenesis. As a consequence, alterations in PPARγ functioning, for instance by inactivating mutations, influences the process of adipogenesis. In our research we focus on the effect of newly identified mutations in the ligand binding domain (LBD) of PPARγ on transcription, coregulator recruitment, and ultimately, adipogenesis.
Chrystal structure of the PPARγ(green)/RXRα(orange) dimer binding to DNA. All amino acid positions mutated in FPLD patients are given in black.
The second project focuses on the characterization of Nuclear Receptor-coregulator interaction. Nuclear receptors are able to bind a broad set of coregulators. In general, certain peptide motifs in coregulators are involved in binding to the LBD domain of nuclear receptors. The motifs LxxLL (coactivators) and LxxxIxxxL (corepressors) both form amphiphatic helices, of which the hydrophobic helical side can interact with a hydrophobic pocket in the NR LBD. Depending on the presence or absence of ligand, or the type of ligand, either a coactivator or a corepressor motif can bind. Using the MARCoNI assay, developed by the Dutch company Pamgene International B.V., we are able to study in a high throughput manner the interaction between a broad set of NRs and a wide variety of coregulator LxxLL/LxxxIxxxL peptides. In the end we hope to discover general rules regarding specificity of coregulator-NR interactions.
Chrystal structure of a LXXLL peptide(yellow) binding to the PPARγLBD(green). Ligand is given in pink.
Latest update: March 2, 2011