• Principal Investigator
  • Male

Prof. dr. N. Zelcer PhD

Position: Associate professor (UHD)
Main activities: Research
Specialisation: Transcriptional regulation of metabolism
foto N. Zelcer is one of the AMC Principal Investigators
Focus of research:

* Contribution of the LXR-IDOL-LDLR axis to cholesterol metabolism

* Identification of novel metabolic genes

* Studying the contribution of the UPS system to metabolism

AMC themes: Cardiovascular Diseases, Metabolic disorders and gastrointestinal diseases
Departments: Medical Biochemistry
Alioui A, Dufour J, Leoni V, Loregger A, Moeton M, Iuliano L, Zerbinati C, Septier A, Val P, Fouache A, Russo V, Volle DH, Lobaccaro JMA, Zelcer N, Baron S, Liver X receptors constrain tumor development and metastasis dissemination in PTEN-deficient prostate cancer. NAT COMMUN 2017;8 (1):445 [PubMed]
Cook ECL, Nelson JK, Sorrentino V, Koenis D, Moeton M, Scheij S, Ottenhoff R, Bleijlevens B, Loregger A, Zelcer N, Identification of the ER-resident E3 ubiquitin ligase RNF145 as a novel LXR-regulated gene. PLOS ONE 2017;12 (2):e0172721 [PubMed]
Hakonen JE, Sorrentino V, Avagliano Trezza R, de Wissel MB, van den Berg M, Bleijlevens B, van Ruissen F, Distel B, Baas F, Zelcer N, Weterman MAJ, LRSAM1-mediated ubiquitylation is disrupted in axonal Charcot-Marie-Tooth disease 2P. HUM MOL GENET 2017;26 (11):2034-2041 [PubMed]
Loregger A, Nelson JK, Zelcer N, Assaying Low-Density-Lipoprotein (LDL) Uptake into Cells. METHODS MOL BIOL 2017;1583:53-63 [PubMed]
Loregger A, Raaben M, Tan J, Scheij S, Moeton M, van den Berg M, Gelberg-Etel H, Stickel E, Roitelman J, Brummelkamp T, Zelcer N, Haploid Mammalian Genetic Screen Identifies UBXD8 as a Key Determinant of HMGCR Degradation and Cholesterol Biosynthesis. ARTERIOSCL THROM VAS 2017;37 (11):2064-2074 [PubMed]
Nelson JK, Koenis DS, Scheij S, Cook ECL, Moeton M, Santos A, Lobaccaro JMA, Baron S, Zelcer N, EEPD1 Is a Novel LXR Target Gene in Macrophages Which Regulates ABCA1 Abundance and Cholesterol Efflux. ARTERIOSCL THROM VAS 2017;37 (3):423-432 [PubMed]
Lu X, Meima ME, Nelson JK, Sorrentino V, Loregger A, Scheij S, Dekkers DHW, Mulder MT, Demmers JAA, M-Dallinga-Thie G, Zelcer N, Danser AHJ, Identification of the (Pro)renin Receptor as a Novel Regulator of Low-Density Lipoprotein Metabolism. CIRC RES 2016;118 (2):222-229 [PubMed]
Nelson JK. Scratching the surface: Regulation of cell surface receptors in cholesterol metabolism. S.l.: s.n.; 2016. 239p. ISBN 978-94-6169-943-5 [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): de Vries CJM, Zelcer N; copromotor(s): )
Nelson JK, Cook ECL, Loregger A, Hoeksema MA, Scheij S, Kovacevic I, Hordijk PL, Ovaa H, Zelcer N, Deubiquitylase Inhibition Reveals Liver X Receptor-independent Transcriptional Regulation of the E3 Ubiquitin Ligase IDOL and Lipoprotein Uptake. J BIOL CHEM 2016;291 (9):4813-4825 [PubMed]
Nelson JK, Sorrentino V, Avagliano Trezza R, Heride C, Urbe S, Distel B, Zelcer N, The Deubiquitylase USP2 Regulates the LDLR Pathway by Counteracting the E3-Ubiquitin Ligase IDOL. CIRC RES 2016;118 (3):410-419 [PubMed]
Tol MJ, Ottenhoff R, van Eijk M, Zelcer N, Aten J, Houten SM, Geerts D, van Roomen C, Bierlaagh MC, Scheij S, Hoeksema MA, Aerts JM, Bogan JS, Dorn GW 2nd, Argmann CA, Verhoeven AJ, A PPARγ-Bnip3 Axis Couples Adipose Mitochondrial Fusion-Fission Balance to Systemic Insulin Sensitivity. DIABETES 2016;65 (9):2591-2605 [PubMed]
Tol MJPM. Deregulation of lysosomal and mitochondrial dynamics in obesity. S.l.: s.n.; 2016. 169p. [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Verhoeven AJ; copromotor(s): Zelcer N, van Eijk MC)
van Loon NM, Zelcer N, Idolizing the clearance of Amyloid-beta by microglia. ANN TRANSL MED 2016;4 (24):536 [PubMed]
de Boussac H, Maqdasy S, Trousson A, Zelcer N, Volle DH, Lobaccaro JMA, Baron S, Enolase is regulated by Liver X Receptors. STEROIDS 2015;99 (Part B):266-271 [PubMed]
Kurakula K, Sommer D, Sokolovic M, Moerland PD, Scheij S, van Loenen PB, Koenis DS, Zelcer N, van Tiel CM, de Vries CJM, LIM-Only Protein FHL2 Is a Positive Regulator of Liver X Receptors in Smooth Muscle Cells Involved in Lipid Homeostasis. MOL CELL BIOL 2015;35 (1):52-62 [PubMed]
Loregger A, Cook ECL, Nelson JK, Moeton M, Sharpe LJ, Engberg S, Karimova M, Lambert G, Brown AJ, Zelcer N, A MARCH6 and IDOL E3 Ubiquitin Ligase Circuit Uncouples Cholesterol Synthesis from Lipoprotein Uptake in Hepatocytes. MOL CELL BIOL 2015;36 (2):285-294 [PubMed]
Fouchier SW, Dallinga-Thie GM, Meijers JCM, Zelcer N, Kastelein JJP, Defesche JC, Hovingh GK, Mutations in STAP1 are associated with autosomal dominant hypercholesterolemia. CIRC RES 2014;115 (6):552-555 [PubMed]
Kizhakkedath P, Loregger A, John A, Bleijlevens B, Al-Blooshi AS, Al-Hosani AH, Al-Nuaimi AM, Al-Gazali L, Zelcer N, Ali BR, Impaired trafficking of the very low density lipoprotein receptor caused by missense mutations associated with dysequilibrium syndrome. BBA-MOL CELL RES 2014;1843 (12):2871-2877 [PubMed]
Sharpe LJ, Cook ECL, Zelcer N, Brown AJ, The UPS and downs of cholesterol homeostasis. TRENDS BIOCHEM SCI 2014;39 (11):527-535 [PubMed]
Sorrentino V. Regulation of cholesterol metabolism: An IDOL-dependent pathway to degrade the LDL-receptor. S.l.: s.n.; 2014. 130p. [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Aerts JMFG; copromotor(s): Zelcer N)
Zelcer N, Sharpe LJ, Loregger A, Kristiana I, Cook ECL, Phan L, Stevenson J, Brown AJ, The E3 ubiquitin ligase MARCH6 degrades squalene monooxygenase and affects 3-hydroxy-3-methyl-glutaryl coenzyme A reductase and the cholesterol synthesis pathway. MOL CELL BIOL 2014;34 (7):1262-1270 [PubMed]
Zelcer N, Westerterp M, Adeno-associated viruses as a method to induce atherosclerosis in mice and hamsters. CIRC RES 2014;114 (11):1672-1674 [PubMed]
Bogie JFJ, Jorissen W, Mailleux J, Nijland PG, Zelcer N, Vanmierlo T, van Horssen J, Stinissen P, Hellings N, Hendriks JJA, Myelin alters the inflammatory phenotype of macrophages by activating PPARs. ACTA NEUROPATHOL COM 2013;1 (1):43-(13 p.) [PubMed]
Pietiäinen V, Vassilev B, Blom T, Wang W, Nelson J, Bittman R, Bäck N, Zelcer N, Ikonen E, NDRG1 functions in LDL receptor trafficking by regulating endosomal recycling and degradation. J CELL SCI 2013;126 (Part 17):3961-3971 [PubMed]
Sorrentino V, Fouchier SW, Motazacker MM, Nelson JK, Defesche JC, Dallinga-Thie GM, Kastelein JJP, Kees Hovingh G, Zelcer N, Identification of a loss-of-function inducible degrader of the low-density lipoprotein receptor variant in individuals with low circulating low-density lipoprotein. EUR HEART J 2013;34 (17):1292-1297 [PubMed]
Sorrentino V, Nelson JK, Maspero E, Marques ARA, Scheer L, Polo S, Zelcer N, The LXR-IDOL axis defines a clathrin-, caveolae-, and dynamin-independent endocytic route for LDLR internalization and lysosomal degradation. J LIPID RES 2013;54 (8):2174-2184 [PubMed]
Do HT, Tselykh TV, Mäkelä J, Ho TH, Olkkonen VM, Bornhauser BC, Korhonen L, Zelcer N, Lindholm D, Fibroblast Growth Factor-21 (FGF21) Regulates Low-density Lipoprotein Receptor (LDLR) Levels in Cells via the E3-ubiquitin Ligase Mylip/Idol and the Canopy2 (Cnpy2)/Mylip-interacting Saposin-like Protein (Msap). J BIOL CHEM 2012;287 (16):12602-12611 [PubMed]
Motazacker MM, Pirruccello J, Huijgen R, Do R, Gabriel S, Peter J, Kuivenhoven JA, Defesche JC, Kastelein JJP, Hovingh GK, Zelcer N, Kathiresan S, Fouchier SW, Advances in genetics show the need for extending screening strategies for autosomal dominant hypercholesterolaemia. EUR HEART J 2012;33 (11):1360-1366 [PubMed]
Sorrentino V, Zelcer N, Post-transcriptional regulation of lipoprotein receptors by the E3-ubiquitin ligase inducible degrader of the low-density lipoprotein receptor. CURR OPIN LIPIDOL 2012;23 (3):213-219 [PubMed]
Weterman MAJ, Sorrentino V, Kasher PR, Jakobs ME, van Engelen BGM, Fluiter K, de Wissel MB, Sizarov A, Nürnberg G, Nürnberg P, Zelcer N, Schelhaas HJ, Baas F, A frameshift mutation in LRSAM1 is responsible for a dominant hereditary polyneuropathy. HUM MOL GENET 2012;21 (2):358-370 [PubMed]
Scotti E, Hong C, Yoshinaga Y, Tu Y, Hu Y, Zelcer N, Boyadjian R, de Jong PJ, Young SG, Fong LG, Tontonoz P, Targeted disruption of the Idol gene alters cellular regulation of the LDLR by sterols and LXR agonists. MOL CELL BIOL 2011;31 (9):1885-1893 [PubMed]
Sorrentino V, Scheer L, Santos A, Reits E, Bleijlevens B, Zelcer N, Distinct functional domains contribute to degradation of the low density lipoprotein receptor (LDLR) by the E3 ubiquitin ligase inducible Degrader of the LDLR (IDOL). J BIOL CHEM 2011;286 (34):30190-30199 [PubMed]
Weissglas-Volkov D, Calkin AC, Tusie-Luna T, Sinsheimer JS, Zelcer N, Riba L, Tino AMV, Ordoñez-Sánchez ML, Cruz-Bautista I, Aguilar-Salinas CA, Tontonoz P, Pajukanta P, The N342S MYLIP polymorphism is associated with high total cholesterol and increased LDL receptor degradation in humans. J CLIN INVEST 2011;121 (8):3062-3071 [PubMed]
Hong C, Duit S, Jalonen P, Out R, Scheer L, Sorrentino V, Boyadjian R, Rodenburg KCW, Foley E, Korhonen L, Lindholm D, Nimpf J, van Berkel TJC, Tontonoz P, Zelcer N, The E3 Ubiquitin Ligase IDOL Induces the Degradation of the Low Density Lipoprotein Receptor Family Members VLDLR and ApoER2. J BIOL CHEM 2010;285 (26):19720-19726 [PubMed]
A-Gonzalez N, Bensinger SJ, Hong C, Beceiro S, Bradley MN, Zelcer N, Deniz J, Ramirez C, Díaz M, Gallardo G, de Galarreta CR, Salazar J, Lopez F, Edwards P, Parks J, Andujar M, Tontonoz P, Castrillo A, Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR. IMMUNITY 2009;31 (2):245-258 [PubMed]
Zelcer N, Hong C, Boyadjian R, Tontonoz P, LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor. SCIENCE 2009;325 (5936):100-104 [PubMed]
Bensinger SJ, Bradley MN, Joseph SB, Zelcer N, Janssen EM, Hausner MA, Shih R, Parks JS, Edwards PA, Jamieson BD, Tontonoz P, LXR signaling couples sterol metabolism to proliferation in the acquired immune response. CELL 2008;134 (1):97-111 [PubMed]
Jiang Q, Lee CYD, Mandrekar S, Wilkinson B, Cramer P, Zelcer N, Mann K, Lamb B, Willson TM, Collins JL, Richardson JC, Smith JD, Comery TA, Riddell D, Holtzman DM, Tontonoz P, Landreth GE, ApoE promotes the proteolytic degradation of Abeta. NEURON 2008;58 (5):681-693 [PubMed]
van de Wetering K, Zelcer N, Kuil A, Feddema W, Hillebrand M, Vlaming MLH, Schinkel AH, Beijnen JH, Borst P, Multidrug resistance proteins 2 and 3 provide alternative routes for hepatic excretion of morphine-glucuronides. MOL PHARMACOL 2007;72 (2):387-394 [PubMed]
Zelcer N, Khanlou N, Clare R, Jiang Q, Reed-Geaghan EG, Landreth GE, Vinters HV, Tontonoz P, Attenuation of neuroinflammation and Alzheimer's disease pathology by liver x receptors. P NATL ACAD SCI USA 2007;104 (25):10601-10606 [PubMed]
Borst P, Zelcer N, van de Wetering K, MRP2 and 3 in health and disease. CANCER LETT 2006;234 (1):51-61 [PubMed]
Borst P, Zelcer N, van de Wetering K, Poolman B, On the putative co-transport of drugs by multidrug resistance proteins. FEBS LETT 2006;580 (4):1085-1093 [PubMed]
Zelcer N, Tontonoz P, Liver X receptors as integrators of metabolic and inflammatory signaling. J CLIN INVEST 2006;116 (3):607-614 [PubMed]
Zelcer N, van de Wetering K, de Waart R, Scheffer GL, Marschall HU, Wielinga PR, Kuil A, Kunne C, Smith A, van der Valk M, Wijnholds J, Elferink RO, Borst P, Mice lacking Mrp3 (Abcc3) have normal bile salt transport, but altered hepatic transport of endogenous glucuronides. J HEPATOL 2006;44 (4):768-775 [PubMed]
Manautou JE, de Waart DR, Kunne C, Zelcer N, Goedken M, Borst P, Elferink RO, Altered disposition of acetaminophen in mice with a disruption of the Mrp3 gene. HEPATOLOGY 2005;42 (5):1091-1098 [PubMed]
Pichler A, Zelcer N, Prior JL, Kuil AJ, Piwnica-Worms D, In vivo RNA interference-mediated ablation of MDR1 P-glycoprotein. CLIN CANCER RES 2005;11 (12):4487-4494 [PubMed]
Wielinga P, Hooijberg JH, Gunnarsdottir S, Kathmann I, Reid G, Zelcer N, van der Born K, de Haas M, van der Heijden I, Kaspers G, Wijnholds J, Jansen G, Peters G, Borst P, The human multidrug resistance protein MRP5 transports folates and can mediate cellular resistance against antifolates. CANCER RES 2005;65 (10):4425-4430 [PubMed]
Zelcer N, Tontonoz P, SUMOylation and PPARgamma: wrestling with inflammatory signaling. CELL METAB 2005;2 (5):273-275 [PubMed]
Zelcer N, van de Wetering K, Hillebrand M, Sarton E, Kuil A, Wielinga PR, Tephly T, Dahan A, Beijnen JH, Borst P, Mice lacking multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide antinociception. P NATL ACAD SCI USA 2005;102 (20):7274-7279 [PubMed]
Assem M, Schuetz EG, Leggas M, Sun D, Yasuda K, Reid G, Zelcer N, Adachi M, Strom S, Evans RM, Moore DD, Borst P, Schuetz JD, Interactions between hepatic Mrp4 and Sult2a as revealed by the constitutive androstane receptor and Mrp4 knockout mice. J BIOL CHEM 2004;279 (21):22250-22257 [PubMed]
Borst P, Balzarini J, Ono N, Reid G, de Vries H, Wielinga P, Wijnholds J, Zelcer N, The potential impact of drug transporters on nucleoside-analog-based antiviral chemotherapy. ANTIVIR RES 2004;62 (1):1-7 [PubMed]
Breedveld P, Zelcer N, Pluim D, Sönmezer O, Tibben MM, Beijnen JH, Schinkel AH, van Tellingen O, Borst P, Schellens JHM, Mechanism of the pharmacokinetic interaction between methotrexate and benzimidazoles: potential role for breast cancer resistance protein in clinical drug-drug interactions. CANCER RES 2004;64 (16):5804-5811 [PubMed]
Cummings J, Zelcer N, Allen JD, Yao D, Boyd G, Maliepaard M, Friedberg TH, Smyth JF, Jodrell DI, Glucuronidation as a mechanism of intrinsic drug resistance in colon cancer cells: contribution of drug transport proteins. BIOCHEM PHARMACOL 2004;67 (1):31-39 [PubMed]
Reid G, Wielinga P, Zelcer N, de Haas M, van Deemter L, Wijnholds J, Balzarini J, Borst P, Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5. MOL PHARMACOL 2003;63 (5):1094-1103 [PubMed]
Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, Wijnholds J, Borst P, The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. P NATL ACAD SCI USA 2003;100 (16):9244-9249 [PubMed]
Zelcer N. MRP2-4, from drug resistance to physiology. S.l.: s.n.; 2003. 132p. [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Borst P; copromotor(s): )
Zelcer N, Huisman MT, Reid G, Wielinga P, Breedveld P, Kuil A, Knipscheer P, Schellens JHM, Schinkel AH, Borst P, Evidence for two interacting ligand binding sites in human multidrug resistance protein 2 (ATP binding cassette C2). J BIOL CHEM 2003;278 (26):23538-23544 [PubMed]
Zelcer N, Reid G, Wielinga P, Kuil A, van der Heijden I, Schuetz JD, Borst P, Steroid and bile acid conjugates are substrates of human multidrug-resistance protein (MRP) 4 (ATP-binding cassette C4). BIOCHEM J 2003;371 (Part 2):361-367 [PubMed]
Zelcer N, Saeki T, Bot I, Kuil A, Borst P, Transport of bile acids in multidrug-resistance-protein 3-overexpressing cells co-transfected with the ileal Na+-dependent bile-acid transporter. BIOCHEM J 2003;369 (Part 1):23-30 [PubMed]
Burg D, Wielinga P, Zelcer N, Saeki T, Mulder GJ, Borst P, Inhibition of the multidrug resistance protein 1 (MRP1) by peptidomimetic glutathione-conjugate analogs. MOL PHARMACOL 2002;62 (5):1160-1166 [PubMed]
Huisman MT, Smit JW, Crommentuyn KML, Zelcer N, Wiltshire HR, Beijnen JH, Schinkel AH, Multidrug resistance protein 2 (MRP2) transports HIV protease inhibitors, and transport can be enhanced by other drugs. AIDS 2002;16 (17):2295-2301 [PubMed]
Zelcer N, Saeki T, Reid G, Beijnen JH, Borst P, Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J BIOL CHEM 2001;276 (49):46400-46407 [PubMed]
Borst P, Zelcer N, van Helvoort A, ABC transporters in lipid transport. BBA-MOL CELL BIOL L 2000;1486 (1):128-144 [PubMed]
Key publications

Sorrentino V, Fouchier SW, Motazacker MM, Nelson JK, Defesche JC, Dallinga-Thie GM, Kastelein JJP, Kees Hovingh G, Zelcer N, Identification of a loss-of-function inducible degrader of the low-density lipoprotein receptor variant in individuals with low circulating low-density lipoprotein. EUR HEART J 2013;34 (17):1292-1297 [PubMed]
Nelson JK, Sorrentino V, Avagliano Trezza R, Heride C, Urbe S, Distel B, Zelcer N, The Deubiquitylase USP2 Regulates the LDLR Pathway by Counteracting the E3-Ubiquitin Ligase IDOL. CIRC RES 2016;118 (3):410-419 [PubMed]
Lu X, Meima ME, Nelson JK, Sorrentino V, Loregger A, Scheij S, Dekkers DHW, Mulder MT, Demmers JAA, M-Dallinga-Thie G, Zelcer N, Danser AHJ, Identification of the (Pro)renin Receptor as a Novel Regulator of Low-Density Lipoprotein Metabolism. CIRC RES 2016;118 (2):222-229 [PubMed]
Zelcer N, Sharpe LJ, Loregger A, Kristiana I, Cook ECL, Phan L, Stevenson J, Brown AJ, The E3 ubiquitin ligase MARCH6 degrades squalene monooxygenase and affects 3-hydroxy-3-methyl-glutaryl coenzyme A reductase and the cholesterol synthesis pathway. MOL CELL BIOL 2014;34 (7):1262-1270 [PubMed]
Zelcer N, Hong C, Boyadjian R, Tontonoz P, LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor. SCIENCE 2009;325 (5936):100-104 [PubMed]


All Publications

Research programmes

Transcriptional regulation of metabolism

 Research program:

 

Faculty
Prof. dr. N. Zelcer PhD

Postdocs
Dr. A. Loregger
Dr. L. Martinelli
Dr. F. Mortensen

PhD Students
E.C.L. Cook MSc
J.E. Hakonen
R.C. Jongkind
N.M. van Loon
J.M.E. Tan

Others
Ing. M. van den Berg
Dr. M. Moeton
Ing. R. Ottenhoff
Ing. S. Scheij

Other research related activities
  • None reported
Current research funding
  • AMC
  • AMC (Vrijgesteld)
  • Europese Unie
  • Nederlandse Hartstichting
  • Stichting AMC Foundation (Vrijgesteld)