• Principal Investigator
  • Male

Dr. S. Kemp PhD

Position: Associate professor (UHD)
Main activities: Research, Teaching
Specialisation: Biochemistry
foto S. Kemp is one of the AMC Principal Investigators
Focus of research:

Identical gene mutations should lead to specific phenotypes; however, this simplistic view does not adequately address the widely varying phenotypes that are commonly observed in many inborn errors of metabolism. Indeed, even identical mutations can lead to widely variable clinical phenotypes, which suggests that additional factors modify disease manifestations.

This situation is clearly exemplified by X-linked adrenoleukodystrophy (ALD), which is the most common leukodystrophy, but also one of the most puzzling inborn errors of metabolism of the central nervous system.

All ALD patients have a mutation in a single gene (ABCD1) and accumulate very-long-chain fatty acids (VLCFA). The disease, however, is characterized by a striking and unpredictable variation in clinical outcomes among men, ranging from adrenal insufficiency to rapidly progressive and fatal cerebral demyelination (cerebral ALD). In adulthood, virtually all men, and 80% of women, with ALD develop progressive spinal cord disease (that is, adrenomyeloneuropathy (AMN)). In the absence of a genotype–phenotype correlation, predicting the disease course is impossible, even within individual families.

Treatment options are limited. For boys with early stage cerebral ALD, a bone-marrow transplant may be curative. However, for AMN, which represents 85% of ALD cases (males and females), no disease modifying therapy is available. The major objective of our research is to resolve the role of VLCFA metabolism in the pathogenesis of ALD and use this knowledge for the development of a rationally based therapy for ALD.

 

 

 

AMC themes: Metabolic disorders and gastrointestinal diseases, Neurological & Psychiatric Disorders
Departments: Laboratory Genetic Metabolic Diseases, Paediatrics: Metabolic Diseases, Paediatrics: Neurology
Alexander SP, Kelly E, Marrion NV, Peters JA, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Buneman OP, Cidlowski JA, Christopoulos A, Davenport AP, Fabbro D, Spedding M, Striessnig J, Davies JA [Contributors: Abbracchio MP, Aldrich R, Al-Hosaini K, Arumugam TV, Attali B, Bäck M, Barnes NM, Bathgate R, Beart PM, Becirovic E, Bettler B, Biel M, Birdsall NJ, Blaho V, Boison D, Bräuner-Osborne H, Bröer S, Bryant C, Burnstock G, Calo G, Catterall WA, Ceruti S, Chan SL, Chandy KG, Chazot P, Chiang N, Chun JJ, Chung JJ, Clapham DE, Clapp L, Connor MA, Cox HM, Davies P, Dawson PA, Decaen P, Dent G, Doherty P, Douglas SD, Dubocovich ML, Fong TM, Fowler CJ, Frantz A, Fuller P, Fumagalli M, Futerman AH, Gainetdinov RR, Gershengorn MA, Goldin A, Goldstein S, Goudet C, Gregory K, Grissmer S, Gundlach AL, Hagenbuch B, Hamann J, Hammond JR, Hancox JC, Hanson J, Hanukoglu I, Hay DL, Hobbs AJ, Hollenberg AN, Holliday ND, Hoyer D, IJzerman AP, Inui KI, Irving AJ, Ishii S, Jacobson KA, Jan LY, Jarvis MF, Jensen R, Jockers R, Kaczmarek LK, Kanai Y, Karnik S, Kellenberger S, Kemp S, Kennedy C, Kerr ID, Kihara Y, Kukkonen J, Larhammar D, Leach K, Lecca D, Leeman S, Leprince J, Lolait SJ, MacEwan D, Maguire JJ, Marshall F, Mazella J, McArdle CA, Michel MC, Miller LJ, Mitolo V, Mizuno H, Monk PN, Mouillac B, Murphy PM, Nahon JL, Nerbonne J, Nichols CG, Norel X, Offermanns S, Palmer LG, Panaro MA, Papapetropoulos A, Perez-Reyes E, Pertwee RG, Pintor S, Pisegna JR, Plant LD, Poyner DR, Prossnitz ER, Pyne S, Ramachandran R, Ren D, Rondard P, Ruzza C, Sackin H, Sanger G, Sanguinetti MC, Schild L, Schiöth H, Schulte G, Schulz S, Segaloff DL, Serhan CN, Singh KD, Slesinger PA, Snutch TP, Sobey CG, Stewart G, Stoddart LA, Summers RJ, Szabo C, Thwaites D, Toll L, Trimmer JS, Tucker S, Vaudry H, Verri T, Vilargada JP, Waldman SA, Ward DT, Waxman SG, Wei AD, Willars GB, Wong SS, Woodruff TM, Wulff H, Ye RD, Yung Y, Zajac JM]] , The concise guide to pharmacology 2017/18: Overview. BRIT J PHARMACOL 2017;174 (Suppl. 1):S1-S16 [PubMed]
Huffnagel IC, van de Beek MC, Showers AL, Orsini JJ, Klouwer FCC, Dijkstra IME, Schielen PC, van Lenthe H, Wanders RJA, Vaz FM, Morrissey MA, Engelen M, Kemp S, Comparison of C26:0-carnitine and C26:0-lysophosphatidylcholine as diagnostic markers in dried blood spots from newborns and patients with adrenoleukodystrophy. MOL GENET METAB 2017;ahead of print [PubMed]
Schackmann MJA. Biochemical and cell biological aspects of X-linked adrenoleukodystrophy. S.l.: s.n.; 2017. 127p. [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Wanders RJA; copromotor(s): Kemp S)
van de Beek MC, Dijkstra IME, Kemp S, Method for Measurement of Peroxisomal Very Long-Chain Fatty Acid Beta-Oxidation and De Novo C26:0 Synthesis Activity in Living Cells Using Stable-Isotope Labeled Docosanoic Acid. METHODS MOL BIOL 2017;1595:45-54 [PubMed]
van de Beek MC, Ofman R, Dijkstra I, Wijburg F, Engelen M, Wanders R, Kemp S, Lipid-induced endoplasmic reticulum stress in X-linked adrenoleukodystrophy. BBA-MOL BASIS DIS 2017;1863 (9):2255-2265 [PubMed]
Kemp S, Huffnagel IC, Linthorst GE, Wanders RJ, Engelen M, Adrenoleukodystrophy - neuroendocrine pathogenesis and redefinition of natural history. NAT REV ENDOCRINOL 2016;12 (10):606-615 [PubMed]
Potze L, Di Franco S, Grandela C, Pras-Raves ML, Picavet DI, van Veen HA, van Lenthe H, Mullauer FB, van der Wel NN, Luyf A, van Kampen AHC, Kemp S, Everts V, Kessler JH, Vaz FM, Medema JP, Betulinic acid induces a novel cell death pathway that depends on cardiolipin modification. ONCOGENE 2016;35 (4):427-437 [PubMed]
Schackmann MJA, Ofman R, van Geel BM, Dijkstra IME, van Engelen K, Wanders RJA, Engelen M, Kemp S, Pathogenicity of novel ABCD1 variants: The need for biochemical testing in the era of advanced genetics. MOL GENET METAB 2016;118 (2):123-127 [PubMed]
van de Beek MC, Dijkstra IME, van Lenthe H, Ofman R, Goldhaber-Pasillas D, Schauer N, Schackmann M, Engelen-Lee JY, Vaz FM, Kulik W, Wanders RJA, Engelen M, Kemp S, C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man. PLOS ONE 2016;11 (4):e0154597 [PubMed]
van Engen CE, Ofman R, Dijkstra IME, van Goethem TJ, Verheij E, Varin J, Vidaud M, Wanders RJA, Aubourg P, Kemp S, Barbier M, CYP4F2 affects phenotypic outcome in adrenoleukodystrophy by modulating the clearance of very long-chain fatty acids. BBA-MOL BASIS DIS 2016;1862 (10):1861-1870 [PubMed]
Engelen M, Barbier M, Dijkstra IME, Schür R, de Bie RM, Verhamme C, Dijkgraaf MGW, Aubourg PA, Wanders RJA, van Geel BM, de Visser M, Poll-The BT, Kemp S, Reply: Age-dependent penetrance among females with X-linked adrenoleukodystrophy. BRAIN 2015;138 (2):e326 [PubMed]
Jackson KA, Glyn-Jones S, Batt ME, Arden NK, Newton JL [Contributors: Allen N, Ao YF, Barker K, Beasley I, Bennell K, Botha N, Doherty M, Cowie C, Hawkes R, Jaques R, Kemp S, Lohmander S, Mackinnon AL, Miller S, Palmer A, Rossiter M, Roos E, Yoshimura N]] , Assessing risk factors for early hip osteoarthritis in activity-related hip pain: a Delphi study. BMJ OPEN 2015;5 (9):e007609 [PubMed]
Schackmann MJA, Ofman R, Dijkstra IME, Wanders RJA, Kemp S, Enzymatic characterization of ELOVL1, a key enzyme in very long-chain fatty acid synthesis. BBA-MOL CELL BIOL L 2015;1851 (2):231-237 [PubMed]
van Geel BM, Poll-The BT, Verrips A, Boelens JJ, Kemp S, Engelen M, Hematopoietic cell transplantation does not prevent myelopathy in X-linked adrenoleukodystrophy: a retrospective study. J INHERIT METAB DIS 2015;38 (2):359-361 [PubMed]
Engelen M, Barbier M, Dijkstra IME, Schür R, de Bie RMA, Verhamme C, Dijkgraaf MGW, Aubourg PA, Wanders RJA, van Geel BM, de Visser M, Poll-The BT, Kemp S, X-linked adrenoleukodystrophy in women: a cross-sectional cohort study. BRAIN 2014;137 (Part 3):693-706 [PubMed]
Engelen M, Kemp S, Poll-The BT, X-linked adrenoleukodystrophy: pathogenesis and treatment. CURR NEUROL NEUROSCI 2014;14 (10):486 [PubMed]
Kemp S. Molecular Genetics of X-linked Adrenoleukodystrophy in: N. N, editor. Encyclopedia of life sciences (eLS). Chichester: John Wiley & Sons Ltd; 2005. 2014, p. a0024277
Pratley RE, Nauck MA, Barnett AH, Feinglos MN, Ovalle F, Harman-Boehm I, Ye J, Scott R, Johnson S, Stewart M, Rosenstock J [Contributors: Adamson K, Ahmann A, Ahn CW, Ajani D, Akright L, Alwine L, Alzohaili O, Andrawis N, Arbañil Huaman H, Arora S, Bailey T, Barnett A, Baron M, Barreda Caceres L, Barrera J, Berg J, Bertenshaw R, Bode B, Bolton D, Brito M, Brock S, Brockmyre A, Broker R, Brusco O Jr, Buynak R, Canadas-Zizzias R, Canas G, Capo J, Castillo Gamarra M, Cathcart H, Catindig EA, Chilka S, Cho YW, Choi DS, Chuck L, Cooper M, Corder C, Cruz H, Darzy K, de la Rosa R, de Teresa L, Degarmo R, D'Emden M, Denopol M, DiGiovanna M, Escalante D, Fakih F, Farris N, Feinglos M, Fillmore R, Fitz-Patrick D, Forker A, Fulcher G, Gabra N, Gabriel J, Gerstman M, Glaser L, Gnudi L, Gonzales Bravo L, Gonzalez E, Graf R, Greenwald M, Grunberger G, Harman-Boehm I, Herskovits T, Higgins A, Hoekstra J, Hollander P, Hubach E, Huff man D, Ison R, Jang HC, Jimeno C, Jones S, Karl J, Kemp S, Ketels C, Kipnes M, Knopke C, Kolettis E, Lacour A, Ledesma G, Lee D, Lefebvre G, Liljenquist D, Lipetz R, Look M, Lucas K, Luna Figueroa A, Maletz L, Marar I, Mathur R, Mayeda S, McCartney M, McGill J, Metz D, Mihalyi D, Min KW, Minuchin O, Mirasol R, Nelson D, Nolan C, Norwood P, Oberoi M, Ovalle F, Pace D, Pace M, Pappas J, Patel N, Patron A, Powell S, Pratley R, Proietto J, Rendell M, Roberts A, Rosen R, Rosenblit P, Rosenstock J, Rothman J, Ruoff G, Russell A, Samuels B, Sanderlin D, Sanders R, Schmidt J, Selam JL, Severance R, Sewell M, Shachar S, Simpson R, Smith T, Solis Villanueva J, Soto A, Sparks J, Stephens J, Stewart R, Streja D, Strzinek R, Sy RA, Teniola S, Tidman R, Toro H, Upender R, Urgeles Planella JR, Valitutto M, Vishlitzky V, Wade R, Wahle J, Weissman P, Williams D, Yao C, Ygpuara MDL, Yue D, Zapata Rincón L]] , Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): a randomised, open-label, multicentre, non-inferiority phase 3 study. LANCET DIABETES ENDO 2014;2 (4):289-297 [PubMed]
Barge-Schaapveld DQCM, Ofman R, Knegt AC, Alders M, Höhne W, Kemp S, Hennekam RCM, Intellectual disability and hemizygous GPD2 mutation. AM J MED GENET A 2013;161A (5):1044-1050 [PubMed]
Engelen M, Ofman R, Dijkgraaf M, van Geel B, de Visser M, Wanders R, Poll-The BT, Kemp S, Comment on the paper "Effect of statin treatment on adrenomyeloneuropathy with cerebral inflammation: a revisit". CLIN NEUROL NEUROSUR 2013;115 (11):2401-2402 [PubMed]
Amorosi CA, Myskóva H, Monti MR, Argaraña CE, Morita M, Kemp S, Dodelson de Kremer R, Dvoráková L, Oller de Ramírez AM, X-Linked Adrenoleukodystrophy: Molecular and Functional Analysis of the ABCD1 Gene in Argentinean Patients. PLOS ONE 2012;7 (12):e52635 [PubMed]
Ebberink MS, Koster J, Visser G, van Spronsen F, Stolte-Dijkstra I, Smit GPA, Fock JM, Kemp S, Wanders RJA, Waterham HR, A novel defect of peroxisome division due to a homozygous non-sense mutation in the PEX11 beta gene. J MED GENET 2012;49 (5):307-313 [PubMed]
Engelen M. Translational studies in X-linked adrenoleukodystrophy. s.l.: s.n.; 2012. 135p. ISBN 9789461914743 [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Poll-The BT, de Visser M; copromotor(s): Kemp S, van Geel BM)
Engelen M, Kemp S, de Visser M, van Geel BM, Wanders RJA, Aubourg P, Poll-The BT, X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. ORPHANET J RARE DIS 2012;7 (1):51 [PubMed]
Engelen M, Schackmann MJA, Ofman R, Sanders RJ, Dijkstra IME, Houten SM, Fourcade S, Pujol A, Poll-The BT, Wanders RJA, Kemp S, Bezafibrate lowers very long-chain fatty acids in X-linked adrenoleukodystrophy fibroblasts by inhibiting fatty acid elongation. J INHERIT METAB DIS 2012;35 (6):1137-1145 [PubMed]
Engelen M, Tran L, Ofman R, Brennecke J, Moser AB, Dijkstra IME, Wanders RJA, Poll-The BT, Kemp S, Bezafibrate for X-Linked Adrenoleukodystrophy. PLOS ONE 2012;7 (7):e41013 [PubMed]
Kemp S, Berger J, Aubourg P, X-linked adrenoleukodystrophy: Clinical, metabolic, genetic and pathophysiological aspects. BBA-MOL BASIS DIS 2012;1822 (9):1465-1474 [PubMed]
Krasemann E, Kemp S, Gal A, Clinical utility gene card for: Adrenoleukodystrophy. EUR J HUM GENET 2012;20 (3):Gene card 1 [PubMed]
Engelen M, van der Kooi AJ, Kemp S, Wanders RJA, Sistermans EA, Waterham HR, Koelman JTM, van Geel BM, de Visser M, X-linked adrenomyeloneuropathy due to a novel missense mutation in the ABCD1 start codon presenting as demyelinating neuropathy. J PERIPHER NERV SYST 2011;16 (4):353-355 [PubMed]
Kemp S, Theodoulou FL, Wanders RJA, Mammalian peroxisomal ABC transporters: from endogenous substrates to pathology and clinical significance. BRIT J PHARMACOL 2011;164 (7):1753-1766 [PubMed]
Wanders RJA, Komen J, Kemp S, Fatty acid omega-oxidation as a rescue pathway for fatty acid oxidation disorders in humans. FEBS J 2011;278 (2):182-194 [PubMed]
Zhang X, de Marcos Lousa C, Schutte-Lensink N, Ofman R, Wanders RJ, Baldwin SA, Baker A, Kemp S, Theodoulou FL, Conservation of targeting but divergence in function and quality control of peroxisomal ABC transporters: an analysis using cross-kingdom expression. BIOCHEM J 2011;436 (3):547-557 [PubMed]
Engelen M, Ofman R, Dijkgraaf MGW, Hijzen M, van der Wardt LA, van Geel BM, de Visser M, Wanders RJA, Poll-The BT, Kemp S, Lovastatin in X-Linked Adrenoleukodystrophy. NEW ENGL J MED 2010;362 (3):276-277 [PubMed]
Fourcade S, Ruiz M, Guilera C, Hahnen E, Brichta L, Naudi A, Portero-Otín M, Dacremont G, Cartier N, Wanders R, Kemp S, Mandel JL, Wirth B, Pamplona R, Aubourg P, Pujol A, Valproic acid induces antioxidant effects in X-linked adrenoleukodystrophy. HUM MOL GENET 2010;19 (10):2005-2014 [PubMed]
Gautron AS, Giquel B, Beaudoin L, Autrusseau E, Speak A, Platt F, Kemp S, Pujol A, Aubourg P, Lehuen A, Invariant NKT cells in adrenoleukodystrophy patients and mice. J NEUROIMMUNOL 2010;229 (1-2):204-211 [PubMed]
Kemp S, Wanders R, Biochemical aspects of x-linked adrenoleukodystrophy. BRAIN PATHOL 2010;20 (4):831-837 [PubMed]
Ofman R, Dijkstra IME, van Roermund CWT, Burger N, Turkenburg M, van Cruchten A, van Engen CE, Wanders RJA, Kemp S, The role of ELOVL1 in very long-chain fatty acid homeostasis and X-linked adrenoleukodystrophy. EMBO MOL MED 2010;2 (3):90-97 [PubMed]
Wanders RJA, Ferdinandusse S, Brites P, Kemp S, Peroxisomes, lipid metabolism and lipotoxicity. BBA-MOL CELL BIOL L 2010;1801 (3):272-280 [PubMed]
Janssen RJRJ, Distelmaier F, Smeets R, Wijnhoven T, Ostergaard E, Jaspers NGJ, Raams A, Kemp S, Rodenburg RJT, Willems PHMG, van den Heuvel LPWJ, Smeitink JAM, Nijtmans LGJ, Contiguous gene deletion of ELOVL7, ERCC8 and NDUFAF2 in a patient with a fatal multisystem disorder. HUM MOL GENET 2009;18 (18):3365-3374 [PubMed]
Sanders RJ. Studies on the omega-oxidation of very long-chain fatty acids in relation to X-linked adrenoleukodystrophy. s.l.: s.n.; 2009. 134p. ISBN 9789088910937 [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Wanders RJA; copromotor(s): Kemp S)
Sanders RJ, Ofman R, Dekker C, Kemp S, Wanders RJA, Enzymatic diagnosis of Sjögren-Larsson syndrome using electrospray ionization mass spectrometry. J CHROMATOGR B 2009;877 (4):451-455 [PubMed]
Engelen M, Kemp S, van Geel BM, Van gen naar ziekte; X-gebonden adrenoleukodystrofie. NED TIJDSCHR GENEESKD 2008;152 (14):804-808 [PubMed]
Engelen M, Ofman R, Mooijer PAW, Poll-The BT, Wanders RJA, Kemp S, Cholesterol-deprivation increases mono-unsaturated very long-chain fatty acids in skin fibroblasts from patients with X-linked adrenoleukodystrophy. BBA-MOL CELL BIOL L 2008;1781 (3):105-111 [PubMed]
Fourcade S, Lopez-Erauskin J, Galino J, Duval C, Naudi A, Jove M, Kemp S, Villarroya F, Ferrer I, Pamplona R, Portero-Otin M, Pujol A, Early oxidative damage underlying neurodegeneration in X-adrenoleukodystrophy. HUM MOL GENET 2008;17 (12):1762-1773 [PubMed]
Kemp S, Valianpour F, Denis S, Ofman R, Sanders RJ, Mooyer P, Barth PG, Wanders RJA, Corrigendum to "Elongation of very long-chain fatty acids is enhanced in X-linked adrenoleukodystrophy" (vol 84, pg 144, 2005). MOL GENET METAB 2008;93 (3):350
Sanders RJ, Ofman R, Dacremont G, Wanders RJA, Kemp S, Characterization of the human omega-oxidation pathway for omega-hydroxy-very-long-chain fatty acids. FASEB J 2008;22 (6):2064-2071 [PubMed]
Kemp S, Wanders RJA, X-linked adrenoleukodystrophy: very long-chain fatty acid metabolism, ABC half-transporters and the complicated route to treatment. MOL GENET METAB 2007;90 (3):268-276 [PubMed]
Wanders RJA, Visser WF, van Roermund CWT, Kemp S, Waterham HR, The peroxisomal ABC transporter family. PFLUG ARCH EUR J PHY 2007;453 (5):719-734 [PubMed]
Gueugnon F, Volodina N, Taouil JE, Lopez TE, Gondcaille C, Grand ASL, Mooijer PAW, Kemp S, Wanders RJA, Savary S, A novel cell model to study the function of the adrenoleukodystrophy-related protein. BIOCHEM BIOPH RES CO 2006;341 (1):150-157 [PubMed]
Linnebank M, Kemp S, Wanders RJA, Kleijer WJ, van der Sterre MLT, Gärtner J, Fliessbach K, Semmler A, Sokolowski P, Köhler W, Schlegel U, Schmidt S, Klockgether T, Wüllner U, Methionine metabolism and phenotypic variability in X-linked adrenoleukodystrophy. NEUROLOGY 2006;66 (3):442-443 [PubMed]
Linnebank M, Semmler A, Kleijer WJ, van der Sterre MLT, Gärtner J, Fliessbach K, Sokolowski P, Köhler W, Schlegel U, Klockgether T, Wanders RJA, Schmidt S, Wüllner U, Kemp S, The cystathionine beta-synthase variant c.844_845ins68 protects against CNS demyelination in X-linked adrenoleukodystrophy. HUM MUTAT 2006;27 (10):1063-1064 [PubMed]
Sanders RJ, Ofman R, Duran M, Kemp S, Wanders RJA, Omega-oxidation of very long-chain fatty acids in human liver microsomes. Implications for X-linked adrenoleukodystrophy. J BIOL CHEM 2006;281 (19):13180-13187 [PubMed]
de Ruijter AJM, Meinsma RJ, Bosma P, Kemp S, Caron HN, van Kuilenburg ABP, Gene expression profiling in response to the histone deacetylase inhibitor BL1521 in neuroblastoma. EXP CELL RES 2005;309 (2):451-467 [PubMed]
Ferrer I, Kapfhammer JP, Hindelang C, Kemp S, Troffer-Charlier N, Broccoli V, Callyzot N, Mooyer P, Selhorst J, Vreken P, Wanders RJA, Mandel JL, Pujol A, Inactivation of the peroxisomal ABCD2 transporter in the mouse leads to late-onset ataxia involving mitochondria, Golgi and endoplasmic reticulum damage. HUM MOL GENET 2005;14 (23):3565-3577 [PubMed]
Kemp S, Valianpour F, Denis S, Ofman R, Sanders RJ, Mooyer P, Barth PG, Wanders RJA, Elongation of very long-chain fatty acids is enhanced in X-linked adrenoleukodystrophy. MOL GENET METAB 2005;84 (2):144-151 [PubMed]
Oezen I, Rossmanith W, Forss-Petter S, Kemp S, Voigtländer T, Moser-Thier K, Wanders RJ, Bittner RE, Berger J, Accumulation of very long-chain fatty acids does not affect mitochondrial function in adrenoleukodystrophy protein deficiency. HUM MOL GENET 2005;14 (9):1127-1137 [PubMed]
Sanders RJ, Ofman R, Valianpour F, Kemp S, Wanders RJA, Evidence for two enzymatic pathways for omega-oxidation of docosanoic acid in rat liver microsomes. J LIPID RES 2005;46 (5):1001-1008 [PubMed]
de Ruijter AJM, Kemp S, Kramer G, Meinsma RJ, Kaufmann JO, Caron HN, van Kuilenburg ABP, The novel histone deacetylase inhibitor BL1521 inhibits proliferation and induces apoptosis in neuroblastoma cells. BIOCHEM PHARMACOL 2004;68 (7):1279-1288 [PubMed]
Kemp S, Valianpour F, Mooyer PAW, Kulik W, Wanders RJA, Method for measurement of peroxisomal very-long-chain fatty acid beta-oxidation in human skin fibroblasts using stable-isotope-labeled tetracosanoic acid. CLIN CHEM 2004;50 (10):1824-1826 [PubMed]
de Ruijter AJM, van Gennip AH, Caron HN, Kemp S, van Kuilenburg ABP, Histone deacetylases (HDACs): characterization of the classical HDAC family. BIOCHEM J 2003;370 (Part 3):737-749 [PubMed]
Heinzer AK, Watkins PA, Lu JF, Kemp S, Moser AB, Li YY, Mihalik S, Powers JM, Smith KD, A very long-chain acyl-CoA synthetase-deficient mouse and its relevance to X-linked adrenoleukodystrophy. HUM MOL GENET 2003;12 (10):1145-1154 [PubMed]
Valianpour F, Selhorst JJM, van Lint LEM, van Gennip AH, Wanders RJA, Kemp S, Analysis of very long-chain fatty acids using electrospray ionization mass spectrometry. MOL GENET METAB 2003;79 (3):189-196 [PubMed]
Heinzer AK, Kemp S, Lu JF, Watkins PA, Smith KD, Mouse very long-chain acyl-CoA synthetase in X-linked adrenoleukodystrophy. J BIOL CHEM 2002;277 (32):28765-28773 [PubMed]
Kemp S, Pujol A, Waterham HR, van Geel BM, Boehm CD, Raymond GV, Cutting GR, Wanders RJ, Moser HW, ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations. HUM MUTAT 2001;18 (6):499-515 [PubMed]
Wei H, Kemp S, McGuinness MC, Moser AB, Smith KD, Pharmacological induction of peroxisomes in peroxisome biogenesis disorders. ANN NEUROL 2000;47 (3):286-296 [PubMed]
Moser HW, Kemp S, Smith KD, Mutational analysis and the pathogenesis of variant X-linked adrenoleukodystrophy phenotypes. ARCH NEUROL-CHICAGO 1999;56 (3):273-275 [PubMed]
Smith KD, Kemp S, Braiterman LT, Lu JF, Wei HM, Geraghty M, Stetten G, Bergin JS, Pevsner J, Watkins PA, X-linked adrenoleukodystrophy: genes, mutations, and phenotypes. NEUROCHEM RES 1999;24 (4):521-535 [PubMed]
Steinberg SJ, Kemp S, Braiterman LT, Watkins PA, Role of very-long-chain acyl-coenzyme A synthetase in X-linked adrenoleukodystrophy. ANN NEUROL 1999;46 (3):409-412 [PubMed]
Kemp S, Wei HM, Lu JF, Braiterman LT, McGuinness MC, Moser AB, Watkins PA, Smith KD, Gene redundancy and pharmacological gene therapy: implications for X-linked adrenoleukodystrophy. NAT MED 1998;4 (11):1261-1268 [PubMed]
Janssen EA, Kemp S, Hensels GW, Sie OG, de Die-Smulders CE, Hoogendijk JE, de Visser M, Bolhuis PA, Connexin32 gene mutations in X-linked dominant Charcot-Marie-Tooth disease (CMTX1). HUM GENET 1997;99 (4):501-505 [PubMed]
Kemp S, Mooyer PA, Bolhuis PA, van Geel BM, Mandel JL, Barth PG, Aubourg P, Wanders RJ, ALDP expression in fibroblasts of patients with X-linked adrenoleukodystrophy. J INHERIT METAB DIS 1996;19 (5):667-674 [PubMed]
Oostra RJ, Kemp S, Bolhuis PA, Bleeker-Wagemakers EM, No evidence for 'skewed' inactivation of the X-chromosome as cause of Leber's hereditary optic neuropathy in female carriers. HUM GENET 1996;97 (4):500-505 [PubMed]
Kemp S, Ligtenberg MJ, van Geel BM, Barth PG, Sarde CO, van Oost BA, Bolhuis PA, Two intronic mutations in the adrenoleukodystrophy gene. HUM MUTAT 1995;6 (3):272-273 [PubMed]
Ligtenberg MJ, Kemp S, Sarde CO, van Geel BM, Kleijer WJ, Barth PG, Mandel JL, van Oost BA, Bolhuis PA, Spectrum of mutations in the gene encoding the adrenoleukodystrophy protein. AM J HUM GENET 1995;56 (1):44-50 [PubMed]
Janssen EA, Hensels GW, van Oost BA, Hamel BC, Kemp S, Baas F, Weber JW, Barth PG, Bolhuis PA, The gene for X-linked myotubular myopathy is located in an 8 Mb region at the border of Xq27.3 and Xq28. NEUROMUSCULAR DISORD 1994;4 (5-6):455-461 [PubMed]
Kemp S, Ligtenberg MJ, van Geel BM, Barth PG, Wolterman RA, Schoute F, Sarde CO, Mandel JL, van Oost BA, Bolhuis PA, Identification of a two base pair deletion in five unrelated families with adrenoleukodystrophy: a possible hot spot for mutations. BIOCHEM BIOPH RES CO 1994;202 (2):647-653 [PubMed]
Kulkens T, Bolhuis PA, Wolterman RA, Kemp S, te Nijenhuis S, Valentijn LJ, Hensels GW, Jennekens FG, de Visser M, Hoogendijk JE, Baas F, Deletion of the serine 34 codon from the major peripheral myelin protein P0 gene in Charcot-Marie-Tooth disease type 1B. NAT GENET 1993;5 (1):35-39 [PubMed]
Schinkel AH, Kemp S, Dollé M, Rudenko G, Wagenaar E, N-glycosylation and deletion mutants of the human MDR1 P-glycoprotein. J BIOL CHEM 1993;268 (10):7474-7481 [PubMed]
Key publications

Engelen M, Barbier M, Dijkstra IME, Schür R, de Bie RMA, Verhamme C, Dijkgraaf MGW, Aubourg PA, Wanders RJA, van Geel BM, de Visser M, Poll-The BT, Kemp S, X-linked adrenoleukodystrophy in women: a cross-sectional cohort study. BRAIN 2014;137 (Part 3):693-706 [PubMed]
Kemp S, Huffnagel IC, Linthorst GE, Wanders RJ, Engelen M, Adrenoleukodystrophy - neuroendocrine pathogenesis and redefinition of natural history. NAT REV ENDOCRINOL 2016;12 (10):606-615 [PubMed]
Kemp S, Berger J, Aubourg P, X-linked adrenoleukodystrophy: Clinical, metabolic, genetic and pathophysiological aspects. BBA-MOL BASIS DIS 2012;1822 (9):1465-1474 [PubMed]
Kemp S, Theodoulou FL, Wanders RJA, Mammalian peroxisomal ABC transporters: from endogenous substrates to pathology and clinical significance. BRIT J PHARMACOL 2011;164 (7):1753-1766 [PubMed]
van de Beek MC, Dijkstra IME, van Lenthe H, Ofman R, Goldhaber-Pasillas D, Schauer N, Schackmann M, Engelen-Lee JY, Vaz FM, Kulik W, Wanders RJA, Engelen M, Kemp S, C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man. PLOS ONE 2016;11 (4):e0154597 [PubMed]


All Publications

Research programmes

Lipid metabolism and Neurotoxicity

Our ALD research focuses on the following questions and objectives:
1) What is the role of VLCFA in the demyelinating process?
2) What is the genetic basis for the different phenotypes in ALD?
3) Which enzymes are important in the synthesis of VLCFA and how are they regulated?,
4) Development of a therapy for ALD, and
5) Provide reliable information on all aspects of ALD via www.x-ald.nl.

During the last years we have:
• Developed methods to analyze synthesis VLCFA synthesis using stable-isotope labeled fatty acids and tandem mass spectrometry (Kemp et al., Mol. Genet. Metab. 2005)
• Identified ELOVL1, a key enzyme involved in VLCFA synthesis (Ofman et al., EMBO Mol. Med. 2010).
• Developed screening assay for the identification of compounds that inhibit VLCFA synthesis and/or toxicity.
• Generated a conditional transgenic mouse with an extra copy of the ELOVL1 that can be activated in a tissue specific to induce VLCFA synthesis (van de Beek et al PLoS One. 2016).
• Demonstrated that
CYP4F2 affects phenotypic outcome in adrenoleukodystrophy by modulating the clearance of very long-chain fatty acids (van Engen et al. Biochim Biophys Acta. 2016).
• Identified proteins that modulate VLCFA toxicity.
• Demonstrated that VLCFA can also be degraded via omega-oxidation. This pathway may function as an escape route (Sanders et al, J.Lipid.Res. 2005; J.Biol.Chem. 2006; FASEB J. 2008;
van Engen et al. Biochim Biophys Acta. 2016).
• Conducted a placebo-controlled study with lovastatin in AMN patients to evaluate the effect of lovastatin on VLCFA in plasma and blood cells (Engelen et al. NEJM. 2010).
• Performed a large study to describe the clinical symptoms in women with ALD (Engelen et al Brain 2014).

The main focus for the research in the next years will be on: 1) the investigation of the therapeutic potential of pharmacological inhibition of VLCFA synthesis, 2) resolving the role that VLCFA play in the pathophysiology of ALD, and 3) the identification of new prognostic biomarkers to improve care for patients with ALD, which is particularly relevant now that newborn screening for ALD is being introduced.

 

Faculty
Dr. S. Kemp PhD

PhD Students
M. van de Beek MSc
Drs. C.E. van Engen MD

Others
Ir. I.M.E. Dijkstra
Dr. M. Engelen
Ing. R. Ofman

Prof. dr. R.J.A. Wanders (Biochemistry & Enzymology of Metabolic Disorders)

Other research related activities
  • Editor, X-linked adrenoleukodystrophy database (www.x-ald.nl)
  • Chairman, European Adrenomyeloneuropathy Board
  • Board of directors / Trustees / Supervisory board, ALD Connect
  • Membership of medical or scientific committee, Belangenvereniging X-ALD
  • Membership of medical or scientific committee, StopALD Foundation, (USA)
Current research funding
  • Bluebird Bio, Inc.
  • The GEIE ELA International
  • Vertex Pharmaceuticals Inc.