Name: Philip Seibler

Title: Dr. rer. nat.

Position: Group leader ‘Applied Stem Cell Biology’

Address: Institute of Neurogenetics, University of Lübeck
Ratzeburger Allee 160, 23538 Lübeck, Germany

Phone: +49-451-31018212; Fax: +49-451-31018204
Email: philip.seibler@neuro.uni-luebeck.de

 

Induced pluripotent stem cells to generate neuronal disease models.

10/2001-10/2006: Studies of Molecular Life Sciences, University of Lübeck, Germany 03/2006-10/2006: Master thesis (Laboratory of Christine Klein, MD), Section of Clinical and Molecular Neurogenetics, University of Lübeck; “Genetische Untersuchung bei Bewegungsstörungen: Feinkartierung zur Lokalisation genetischer Ursachen bei spinocerebellärer Ataxie bzw. Restless-legs-Syndrom sowie Mutationsanalyse bei Patienten mit Morbus Parkinson“ Master of Science 11/2006-10/2011: Doctoral thesis (Laboratory of Christine Klein, MD), Section of Clinical and Molecular Neurogenetics, University of Lübeck; “Molecular studies of two genetic movement disorders: PRKRA-linked dystonia and PINK1-linked Parkinson disease” PhD (Dr. rer. nat.) 01/2009-09/2010: Research fellow (Laboratory of Dimitri Krainc, MD, PhD), MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Boston, USA; “Impact of PINK1 mutations in neurons derived from induced pluripotent stem cells” 11/2011-03/2016: Group leader (Institute of Neurogenetics, University of Lübeck) 04/2016-03/2017: Research fellow (Laboratory of Matt Farrer, PhD), Centre for Applied Neurogenetics, University of British Columbia, Vancouver, Canada; “Dopamine metabolism and electric activity in iPS-derived neurons” 04/2017-09/2019: Professor for Applied Stem Cell Biology (University of Lübeck) 10/2019-present: Group leader ‘Applied Stem Cell Biology’ (Institute of Neurogenetics, University of Lübeck)

2009: International Research Fellowship awarded by the German Academic Exchange Service (DAAD); Harvard Medical School, Boston, USA


2011: Young Investigator Award of the German Society of Neurogenetics

2014: BioMedTec Founders Award

2016-2017: International Research Fellowship awarded by the German Research Foundation (DFG); University of British Columbia, Vancouver, Canada

“Identification of new modifier genes of TAF1 protein expression” Principal Investigator: Philip Seibler Funding agency: Massachusetts General Hospital (CCXDP) Funding period: 2019–2020 Amount: $ 109,450 “Establishing a pipeline for individualized CIBD cellular models based on iPSCs” Principal Investigator: Philip Seibler Funding agency: Cluster of Excellence (DFG) Funding period: 2017–2018 Amount: € 47,500 “ProtectMove (FOR 2488); Subproject: Reduced Penetrance in Parkin and PINK1 Deficiency: Prevalence, Genetic Modifiers, and Protective Mechanism” Principal Investigator: Philip Seibler Funding agency: German Research Society (DFG) Funding period: 2016–2020 (renewable) Amount: € 329,725 “DYSTRACT; Subproject: “Modeling dystonia in an endogenous human cellular system: Platform and characterization of iPSC-derived neurons from patients with monogenic isolated dystonia” Principal Investigator: Philip Seibler Funding agency: Federal Ministry of Research and Education (BMBF) Funding period: 2016–2019 Amount: € 150,550 “Building up a collaborative resource of biomaterials to unravel the genetic cause and molecular pathways of XDP and to enable comprehensive – omics approaches and drug screening” Principal Investigator: Philip Seibler Funding agency: Massachusetts General Hospital (CCXDP) Funding period: 2015–2018 Amount: € 91,340
  • Member of the Scientific Advisory Board of the EU-funded SysMedPD consortium (2017-present)
  • Member of the Cluster of Excellence Program “Precision Medicine in Chronic Inflammation” (PMI) (2018-present)
  • Annals of Neurology
  • Neurobiology of Disease
  • Neurological Research and Practice
  • Scientific Reports
  • Neuroscience Letters
  • Brain and Behavior
  • Frontiers Cellular Neuroscience
  • Fondazione Telethon
  • Organization and teaching of the lecture series “Molecular Neurobiomedicine” within the Master program Molecular Life Science (2013-present)
  • Organization and teaching of the seminar “Stem Cell Technology” within the Bachelor program Molecular Life Science (2018-present)
  1. Seibler P. Mitochondrial Parkin recruitment is impaired in neurons derived from mutant PINK1 iPS cells. NGFN network meeting “Functional Genomics of Parkinson’s Disease”, Tübingen, Germany, November 2010.
  2. Seibler P. Etablierung eines humanen neuronalen Zellmodells für das PINK1-Parkinsonsyndrom mittels iPS-Zellen. Annual Congress of the German Society of Neurology, Wiesbaden, Germany, September 2011.
  3. Seibler P. Mitochondrial Parkin recruitment is impaired in neurons derived from mutant PINK1 iPS cells. German Society of Neurogenetics, Erlangen, Germany, October 2011.
  4. Seibler P. Modeling genetic and idiopathic Parkinson’s disease with iPS cell-derived neurons. StemBANCC General Assembly Meeting, Oxford Parkinson’s Disease Centre, Oxford, UK, March 2013.
  5. Seibler P. Modeling Parkinson disease using induced pluripotent stem cell-derived neurons. Scientific seminar, Medical proteome centre, University of Bochum, Germany, May 2014.
  6. Seibler P. Overexpression of SLP-2 rescues mitochondrial phenotypes in iPSC-derived neurons from patients with Parkin-linked Parkinson’s disease. StemBANCC General Assembly Meeting, Novo Nordisk A/S, Kopenhagen, Denmark, September 2015.
  7. Seibler P. Applied Stem Cell Biology. Cluster of Excellence Retreat „Inflammation at Interfaces“, Timmendorfer Strand, Germany, July 2017.
  8. Seibler P. Etablierung eines endogenen humanen Zellmodells für Dystonien: Biobank und Charakterisierung von Neuronen aus iPS-Zellen von Patienten mit genetischer Dystonie. Annual Congress of the German Society of Neurology, Leipzig, Germany, September 2017.
  9. Seibler P. iPS Platform. 2nd Research Workshop Technologies and Resources at the University of Lübeck, Lübeck, Germany, September 2017.
  10. Seibler P. Organization and Co-Chair of the symposium „Erforschung neuronaler Bewegungsstörungen mittels induzierter pluripotenter Stammzellen“. Annual Congress of the German Society of Neurology, Berlin, October 2018.
  11. Seibler P. Modeling dystonia in an endogenous human cellular system. Elucidation of novel genetic causes and modifiers for dystonia. Deutscher Kongress für Parkinson und Bewegungsstörungen, Düsseldorf, Germany, March 2019.
  12. Seibler P. Applied Stem Cell Biology. Scientific seminar, CENTOGENE AG, Rostock, Germany, September 2019.
  1. Seibler P, Klein C. Stimulus-triggered acquisition of pluripotency: Revolutionizing human disease modeling and regenerative therapies? Mov Disord. 2014;29:451.
  2. Rakovic A, Seibler P, Klein C. iPS models of Parkin and PINK1. Biochem Soc Trans. 2015;43:302-307.
  3. Kulikovskaja L, Seibler P. Dopamine oxidation mediates a time-dependent pathological cascade in Parkinson’s disease. Mov Disord. 2018;33:250
  4. Seibler P, Klein C. iPSC-Derived Dopaminergic Neurons for Parkinson’s Disease. Encycl Tissue Eng Regen Med. 2019;483–492.
  1. Berenguer-Escuder C, Grossmann D, Massart F, Antony P, Burbulla LF, Glaab E, Imhoff S, Trinh J, Seibler P, Grünewald A, Krüger R. Variants in Miro1 Cause Alterations of ER-Mitochondria Contact Sites in Fibroblasts from Parkinson’s Disease Patients. J Clin Med 2020;12
  2. Dulovic-Mahlow M, Lukomska A, Diaw SH, Balck A, Borsche M, Grütz K, Lenz I, Rudolph F, Lohmann K, Klein C, Seibler P. Generation and characterization of human-derived iPSC lines from three pairs of monozygotic twins discordant for Parkinson’s disease. Stem Cell Res 2019:101629.
  3. Balck A, Borsche M, Kasten M, Lohmann K, Seibler P, Brüggemann N, Klein C. Discordance in monozygotic Parkinson’s disease twins – continuum or dichotomy? Ann Clin Transl Neurol 2019;6:1102-1105.
  4. Ouzren N, Delcambre S, Ghelfi J, Seibler P, Farrer MJ, König IR, Aasly JO, Trinh J, Klein C, Grünewald A. Mitochondrial DNA Deletions Discriminate Affected from Unaffected LRRK2 Mutation Carriers. Ann Neurol 2019;2:324-326.
  5. Baumann H, Jahn M, Muenchau A, Trilck-Winkler M, Lohmann K, Seibler P. Generation and characterization of eight human-derived iPSC lines from affected and unaffected THAP1 mutation carriers. Stem Cell Res 2018:60-64.
  6. Seibler P, Burbulla LF, Dulovic M, Zittel S, Heine J, Schmidt T, Rudolph F, Westenberger A, Rakovic A, Münchau A, Krainc D, Klein C. Iron overload is accompanied by mitochondrial and lysosomal dysfunction in WDR45 mutant cells. Brain 2018;10:3052-3064.
  7. Rakovic A, Domingo A, Grütz K, Kulikovskaja L, Capetian P, Cowley SA, Lenz I, Brüggemann N, Rosales R, Jamora D, Rolfs A, Seibler P, Westenberger A, König I, Klein C. Genome editing in induced pluripotent stem cells rescues TAF1 levels in X-linked dystonia-parkinsonism. Mov Disord 2018;7:1108-1118.
  8. Vulinovic F, Krajka V, Hausrat TJ, Seibler P, Alvarez-Fischer D, Madoev H, Park JS, Kumar KR, Sue CM, Lohmann K, Kneussel M, Klein C, Rakovic A. Motor protein binding and mitochondrial transport are altered by pathogenic TUBB4A variants. Hum Mutat 2018;12:1901-1915.
  9. Trillhaase A, Haferkamp U, Rangnau A, Märtens M, Schmidt B, Trilck M, Seibler P, Aherrahrou R, Erdmann J, Aherrahrou Z. Differentiation of human iPSCs into VSMCs and generation of VSMC-derived calcifying vascular cells. Stem Cell Res 2018:62-70.
  10. Capetian P, Stanslowsky N, Bernhardi E, Grütz K, Domingo A, Brüggemann N, Naujock M, Seibler P, Klein C, Wegner F. Altered glutamate response and calcium dynamics in iPSC-derived striatal neurons from XDP patients. Exp Neurol 2018:47-58.
  11. Valadas JS, Esposito G, Vandekerkhove D, Miskiewicz K, Deaulmerie L, Raitano S, Seibler P, Klein C, Verstreken P. ER Lipid Defects in Neuropeptidergic Neurons Impair Sleep Patterns in Parkinson’s Disease. Neuron 2018;6:1155-1169.e6.
  12. Pauly MG, Krajka V, Stengel F, Seibler P, Klein C, Capetian P. Adherent vs. Free-Floating Neural Induction by Dual SMAD Inhibition for Neurosphere Cultures Derived from Human Induced Pluripotent Stem Cells. Front Cell Dev Biol 2018:3.
  13. Kulikovskaja L, Seibler P. Dopamine oxidation mediates a time-dependent pathological cascade in Parkinson’s disease. Mov Disord 2017;2:250.
  14. Zanon A, Kalvakuri S, Rakovic A, Foco L, Guida M, Schwienbacher C, Serafin A, Rudolph F, Trilck M, Grünewald A, Stanslowsky N, Wegner F, Giorgio V, Lavdas AA, Bodmer R, Pramstaller PP, Klein C, Hicks AA, Pichler I, Seibler P. SLP-2 interacts with Parkin in mitochondria and prevents mitochondrial dysfunction in Parkin-deficient human iPSC-derived neurons and Drosophila. Hum Mol Genet 2017;13:2412-2425.
  15. Grütz K, Seibler P, Weissbach A, Lohmann K, Carlisle FA, Blake DJ, Westenberger A, Klein C, Grünewald A. Faithful SGCE imprinting in iPSC-derived cortical neurons: an endogenous cellular model of myoclonus-dystonia. Sci Rep 2017:41156.
  16. Vos M, Geens A, Böhm C, Deaulmerie L, Swerts J, Rossi M, Craessaerts K, Leites EP, Seibler P, Rakovic A, Lohnau T, De Strooper B, Fendt SM, Morais VA, Klein C, Verstreken P. Cardiolipin promotes electron transport between ubiquinone and complex I to rescue PINK1 deficiency. J Cell Biol 2017;3:695-708.
  17. Capetian P, Azmitia L, Pauly MG, Krajka V, Stengel F, Bernhardi EM, Klett M, Meier B, Seibler P, Stanslowsky N, Moser A, Knopp A, Gillessen-Kaesbach G, Nikkhah G, Wegner F, Döbrössy M, Klein C. Plasmid-Based Generation of Induced Neural Stem Cells from Adult Human Fibroblasts. Front Cell Neurosci 2016:245.
  18. Rakovic A, Seibler P, Klein C. iPS models of Parkin and PINK1. Biochem Soc Trans 2015;2:302-307.
  19. Munsie LN, Milnerwood AJ, Seibler P, Beccano-Kelly DA, Tatarnikov I, Khinda J, Volta M, Kadgien C, Cao LP, Tapia L, Klein C, Farrer MJ. Retromer-dependent neurotransmitter receptor trafficking to synapses is altered by the Parkinson’s disease VPS35 mutation p.D620N. Hum Mol Genet 2014;6:1691-1703.
  20. Erogullari A, Hollstein R, Seibler P, Braunholz D, Koschmidder E, Depping R, Eckhold J, Lohnau T, Gillessen-Kaesbach G, Grünewald A, Rakovic A, Lohmann K, Kaiser FJ. THAP1, the gene mutated in DYT6 dystonia, autoregulates its own expression. Biochim Biophys Acta 2014;11:1196-1204.
  21. Vulinovic F, Lohmann K, Rakovic A, Capetian P, Alvarez-Fischer D, Schmidt A, Weißbach A, Erogullari A, Kaiser FJ, Wiegers K, Ferbert A, Rolfs A, Klein C, Seibler P. Unraveling cellular phenotypes of novel TorsinA/TOR1A mutations. Hum Mutat 2014;9:1114-1122.
  22. Seibler P, Klein C. Stimulus-triggered acquisition of pluripotency: revolutionizing human disease modeling and regenerative therapies? Mov Disord 2014;4:451.
  23. Morais VA, Haddad D, Craessaerts K, De Bock PJ, Swerts J, Vilain S, Aerts L, Overbergh L, Grünewald A, Seibler P, Klein C, Gevaert K, Verstreken P, De Strooper B. PINK1 loss-of-function mutations affect mitochondrial complex I activity via NdufA10 ubiquinone uncoupling. Science 2014;6180:203-207.
  24. Doss S, Lohmann K, Seibler P, Arns B, Klopstock T, Zühlke C, Freimann K, Winkler S, Lohnau T, Drungowski M, Nürnberg P, Wiegers K, Lohmann E, Naz S, Kasten M, Bohner G, Ramirez A, Endres M, Klein C. Recessive dystonia-ataxia syndrome in a Turkish family caused by a COX20 (FAM36A) mutation. J Neurol 2013;1:207-212.
  25. Trilck M, Hübner R, Seibler P, Klein C, Rolfs A, Frech MJ. Niemann-Pick type C1 patient-specific induced pluripotent stem cells display disease specific hallmarks. Orphanet J Rare Dis 2013:144.
  26. Arif B, Kumar KR, Seibler P, Vulinovic F, Fatima A, Winkler S, Nürnberg G, Thiele H, Nürnberg P, Jamil AZ, Brüggemann A, Abbas G, Klein C, Naz S, Lohmann K. A novel OPA3 mutation revealed by exome sequencing: an example of reverse phenotyping. JAMA Neurol 2013;6:783-787.
  27. Rakovic A, Shurkewitsch K, Seibler P, Grünewald A, Zanon A, Hagenah J, Krainc D, Klein C. Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)-dependent ubiquitination of endogenous Parkin attenuates mitophagy: study in human primary fibroblasts and induced pluripotent stem cell-derived neurons. J Biol Chem 2012;4:2223-2237.
  28. Grünewald A, Arns B, Seibler P, Rakovic A, Münchau A, Ramirez A, Sue CM, Klein C. ATP13A2 mutations impair mitochondrial function in fibroblasts from patients with Kufor-Rakeb syndrome. Neurobiol Aging 2012;8:1843.e1-7.
  29. Seibler P, Graziotto J, Jeong H, Simunovic F, Klein C, Krainc D. Mitochondrial Parkin recruitment is impaired in neurons derived from mutant PINK1 induced pluripotent stem cells. J Neurosci 2011;16:5970-5976.
  30. Rakovic A, Grünewald A, Seibler P, Ramirez A, Kock N, Orolicki S, Lohmann K, Klein C. Effect of endogenous mutant and wild-type PINK1 on Parkin in fibroblasts from Parkinson disease patients. Hum Mol Genet 2010;16:3124-3137.
  31. Seibler P, Djarmati A, Langpap B, Hagenah J, Schmidt A, Brüggemann N, Siebner H, Jabusch HC, Altenmüller E, Münchau A, Lohmann K, Klein C. A heterozygous frameshift mutation in PRKRA (DYT16) associated with generalised dystonia in a German patient. Lancet Neurol 2008;5:380-381.
  32. Moro E, Volkmann J, König IR, Winkler S, Hiller A, Hassin-Baer S, Herzog J, Schnitzler A, Lohmann K, Pinsker MO, Voges J, Djarmatic A, Seibler P, Lozano AM, Rogaeva E, Lang AE, Deuschl G, Klein C. Bilateral subthalamic stimulation in Parkin and PINK1 parkinsonism. Neurology 2008;14:1186-1191.