Aleksander Rakovic, PhD

Research Group Leader

Name: Aleksandar Rakovic

Date of Birth: June 10st, 1976

Place of Birth: Belgrade, Serbia

Position/Title: Research Group Leader at the Institute of Neurogenetics

Address: Institute of Neurogenetics, University of Lübeck
Maria-Goeppert-Str.1, 23562 Lübeck, Germany

Phone: +49-451-3101 8203; Fax: +49 451 3101-8204
Email: aleksandar.rakovic@neuro.uni-luebeck.de

1995-2005: Studies of Biology (University of Belgrade, Belgrade, Serbia)

2006-2007: PhD Thesis (Laboratory for Radiobiology and Molecular Genetics, Institute of Nuclear Sciences, Belgrade, Serbia)

2007-2012: PhD Thesis (Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck, Germany)

2012-2013: Postdoctoral Researcher (Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck, Germany)

2016-2017: Research Fellow (SickKids, University of Toronto, Canada)

2013-present: Leader of the research group “Molecular mechanisms of Parkinson’s disease” (Institute of Neurogenetics, University of Lübeck)

2007:  Scholarship from Department of Neurology, University of Lübeck, Germany

2007:  Scholarship from German Academic Exchange Service (DAAD)

2011: Travel award from the Movement Disorder Society (MDS)

2014: Prize for the Best Doctoral Thesis in the MINT Section (Mathematics, Engineering, Natural, and Technical Sciences) of the University of Lübeck

Stipends and Scholarships

2007: Scholarship from Department of Neurology, University of Lübeck, Lübeck, Germany 2007: Deutscher Akademischer Austauch Dienst (DAAD) Foundation’s Kontaktstipendium. 2013-2014:   Intramural funding (E20-2013), University of Lübeck, Lübeck, Germany 2014-2017:   German Research Foundation (DFG, RA 2614/1-1) 2016-2019:   German Research Foundation (DFG, RA 2614/2-1)

Grants

E20-2013 “Exploring the role of mitophagy in the pathogenesis of Parkinson disease using genetic parkinsonism as a model” Principal Investigator: Aleksandar Rakovic Funding agency: University of Lübeck Funding period: 2013-2014 Amount: € 75,000 “Molecular characterization of TUBB4 mutations” Principal Investigator: Aleksandar Rakovic Funding agency: German Research Society (DFG) Funding period: 2015-2018 Amount: € 273,650 “Reduced penetrance in hereditary movement disorders: Elucidating mechanisms of endogenous disease protection (FOR 2488, P3)” Principal Investigator: Aleksandar Rakovic Funding agency: German Research Society (DFG) Funding period: 2016–2020 (renewable) Amount: € 111,125 “Identification of new modifier genes of TAF1 protein expression” Principal Investigator: Aleksandar Rakovic Funding agency: Massachusetts General Hospital (CCXDP) Funding period: 2020–2021 Amount: € 90,779  

Journals

  • Annals of Neurology
  • Human Molecular Genetics
  • Trends in Neuroscience

Grants  

  • German Research Foundation (DFG)
  • The Telethon Foundation (Italy)

Teaching

  • Neurogenetics seminar series
  • Neurobiomedicine lecture series
  • Biology of Model Organisms in Molecular Biology Research (Vertebrates-Danio rerio)
  • Weekly journal club for graduate and undergraduate students

Invited Talks

  1. Rakovic A. Parkinson disease and mitochondrial quality control. LCSB, University of Luxemburg. December 2014.
  2. Rakovic A. Mitochondrial Turnover in Parkinson’s Disease: Is it All About Autophagy? 20th International Congress of Parkinson´s Disease and Movement Disorders, Berlin, Germany, June 2016
  3. Rakovic A. Mitochondrial dysfunction in Parkinson’s disease. Role of PINK1 and Parkin. Zoological Institute, TU Braunschweig, Germany. April 2018.
  4. Rakovic A. CRISPR/Cas9-based fluorescent tyrosine hydroxylase-reporter line. Free talk. 91th annual meeting of the German Society of Neurology in Berlin, Germany, November 2018.
  1. Rakovic A, Klein C, Seibler P. iPS models of Parkin and PINK1. Biochem Soc Trans. 2015 Apr;43(2):302-7. Review.
  1. 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 2019;12:2444.
  2. Schiemenz C, Westenberger A, Tanzer K, Grütz K, Borsche M, Mahlke G, Schaake S, Rakovic A, Aherrahrou Z, Erdmann J, Klein C, Alvarez-Fischer D. Osteoclast imbalance in primary familial brain calcification: evidence for its role in brain calcification. Brain 2019;1:e1.
  3. Westenberger A, Reyes CJ, Saranza G, Dobricic V, Hanssen H, Domingo A, Laabs BH, Schaake S, Pozojevic J, Rakovic A, Grütz K, Begemann K, Walter U, Dressler D, Bauer P, Rolfs A, Münchau A, Kaiser FJ, Ozelius LJ, Jamora RD, Rosales RL, Diesta CCE, Lohmann K, König IR, Brüggemann N, Klein C. A hexanucleotide repeat modifies expressivity of X-linked dystonia parkinsonism. Ann Neurol 2019;6:812-822.
  4. Guida M, Zanon A, Montibeller L, Lavdas AA, Ladurner J, Pischedda F, Rakovic A, Domingues FS, Piccoli G, Klein C, Pramstaller PP, Hicks AA, Pichler I. Parkin Interacts with Apoptosis-Inducing Factor and Interferes with Its Translocation to the Nucleus in Neuronal Cells. Int J Mol Sci 2019;3
  5. 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 2019;12:2444.
  6. 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, Philip S. Corrigendum: SLP-2 interacts with Parkin in mitochondria and prevents mitochondrial dysfunction in Parkin-deficient human iPSC-derived neurons and Drosophila. Hum Mol Genet 2018;7:1225.
  7. Rakovic A, Ziegler J, Mårtensson CU, Prasuhn J, Shurkewitsch K, König P, Paulson HL, Klein C. PINK1-dependent mitophagy is driven by the UPS and can occur independently of LC3 conversion. Cell Death Differ 2018;8:1428-1441.
  8. Chakraborty J, von Stockum S, Marchesan E, Caicci F, Ferrari V, Rakovic A, Klein C, Antonini A, Bubacco L, Ziviani E. USP14 inhibition corrects an in vivo model of impaired mitophagy. EMBO Mol Med 2018;11
  9. 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.
  10. 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.
  11. Prasuhn J, Mårtensson CU, Krajka V, Klein C, Rakovic A. Genome-Edited, TH-expressing Neuroblastoma Cells as a Disease Model for Dopamine-Related Disorders: A Proof-of-Concept Study on DJ-1-deficient Parkinsonism. Front Cell Neurosci 2018:426.
  12. Hebert E, Borngräber F, Schmidt A, Rakovic A, Brænne I, Weissbach A, Hampf J, Vollstedt EJ, Größer L, Schaake S, Müller M, Manzoor H, Jabusch HC, Alvarez-Fischer D, Kasten M, Kostic VS, Gasser T, Zeuner KE, Kim HJ, Jeon B, Bauer P, Altenmüller E, Klein C, Lohmann K. Functional Characterization of Rare RAB12 Variants and Their Role in Musician’s and Other Dystonias. Genes (Basel) 2017;10
  13. Vulinovic F, Schaake S, Domingo A, Kumar KR, Defazio G, Mir P, Simonyan K, Ozelius LJ, Brüggemann N, Chung SJ, Rakovic A, Lohmann K, Klein C. Screening study of TUBB4A in isolated dystonia. Parkinsonism Relat Disord 2017:118-120.
  14. Lohmann K, Redin C, Tönnies H, Bressman SB, Subero JIM, Wiegers K, Hinrichs F, Hellenbroich Y, Rakovic A, Raymond D, Ozelius LJ, Schwinger E, Siebert R, Talkowski ME, Saunders-Pullman R, Klein C. Complex and Dynamic Chromosomal Rearrangements in a Family With Seemingly Non-Mendelian Inheritance of Dopa-Responsive Dystonia. JAMA Neurol 2017;7:806-812.
  15. 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.
  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. Rakovic A, Seibler P, Klein C. iPS models of Parkin and PINK1. Biochem Soc Trans 2015;2:302-307.
  18. Wortmann SB, Ziętkiewicz S, Kousi M, Szklarczyk R, Haack TB, Gersting SW, Muntau AC, Rakovic A, Renkema GH, Rodenburg RJ, Strom TM, Meitinger T, Rubio-Gozalbo ME, Chrusciel E, Distelmaier F, Golzio C, Jansen JH, van Karnebeek C, Lillquist Y, Lücke T, Õunap K, Zordania R, Yaplito-Lee J, van Bokhoven H, Spelbrink JN, Vaz FM, Pras-Raves M, Ploski R, Pronicka E, Klein C, Willemsen MA, de Brouwer AP, Prokisch H, Katsanis N, Wevers RA. CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder. Am J Hum Genet 2015;2:245-257.
  19. 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.
  20. 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.
  21. Deuse T, Hua X, Wang D, Maegdefessel L, Heeren J, Scheja L, Bolaños JP, Rakovic A, Spin JM, Stubbendorff M, Ikeno F, Länger F, Zeller T, Schulte-Uentrop L, Stoehr A, Itagaki R, Haddad F, Eschenhagen T, Blankenberg S, Kiefmann R, Reichenspurner H, Velden J, Klein C, Yeung A, Robbins RC, Tsao PS, Schrepfer S. Dichloroacetate prevents restenosis in preclinical animal models of vessel injury. Nature 2014;7502:641-644.
  22. Zanon A, Rakovic A, Blankenburg H, Doncheva NT, Schwienbacher C, Serafin A, Alexa A, Weichenberger CX, Albrecht M, Klein C, Hicks AA, Pramstaller PP, Domingues FS, Pichler I. Profiling of Parkin-binding partners using tandem affinity purification. PLoS One 2013;11:e78648.
  23. Lohmann K, Wilcox RA, Winkler S, Ramirez A, Rakovic A, Park JS, Arns B, Lohnau T, Groen J, Kasten M, Brüggemann N, Hagenah J, Schmidt A, Kaiser FJ, Kumar KR, Zschiedrich K, Alvarez-Fischer D, Altenmüller E, Ferbert A, Lang AE, Münchau A, Kostic V, Simonyan K, Agzarian M, Ozelius LJ, Langeveld AP, Sue CM, Tijssen MA, Klein C. Whispering dysphonia (DYT4 dystonia) is caused by a mutation in the TUBB4 gene. Ann Neurol 2013;4:537-545.
  24. 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.
  25. 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.
  26. Osmanovic A, Dendorfer A, Erogullari A, Uflacker N, Braunholz D, Rakovic A, Vierke G, Gil-Rodríguez C, Münchau A, Albrecht M, Brüggemann N, Gillessen-Kaesbach G, Klein C, Lohmann K, Kaiser FJ. Truncating mutations in THAP1 define the nuclear localization signal. Mov Disord 2011;8:1565-1567.
  27. Rakovic A, Grünewald A, Voges L, Hofmann S, Orolicki S, Lohmann K, Klein C. PINK1-Interacting Proteins: Proteomic Analysis of Overexpressed PINK1. Parkinsons Dis 2011:153979.
  28. Rakovic A, Grünewald A, Kottwitz J, Brüggemann N, Pramstaller PP, Lohmann K, Klein C. Mutations in PINK1 and Parkin impair ubiquitination of Mitofusins in human fibroblasts. PLoS One 2011;3:e16746.
  29. Kaiser FJ, Osmanoric A, Rakovic A, Erogullari A, Uflacker N, Braunholz D, Lohnau T, Orolicki S, Albrecht M, Gillessen-Kaesbach G, Klein C, Lohmann K. The dystonia gene DYT1 is repressed by the transcription factor THAP1 (DYT6). Ann Neurol 2010;4:554-559.
  30. Grünewald A, Voges L, Rakovic A, Kasten M, Vandebona H, Hemmelmann C, Lohmann K, Orolicki S, Ramirez A, Schapira AH, Pramstaller PP, Sue CM, Klein C. Mutant Parkin impairs mitochondrial function and morphology in human fibroblasts. PLoS One 2010;9:e12962.
  31. 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.
  32. Brüggemann N, Kock N, Lohmann K, König IR, Rakovic A, Hagenah J, Schmidt A, Ziegler A, Jabusch HC, Siebner H, Altenmüller E, Münchau A, Klein C. The D216H variant in the DYT1 gene: a susceptibility factor for dystonia in familial cases? Neurology 2009;16:1441-1443.
  33. Rakovic A, Stiller B, Djarmati A, Flaquer A, Freudenberg J, Toliat MR, Linnebank M, Kostic V, Lohmann K, Paus S, Nürnberg P, Kubisch C, Klein C, Wüllner U, Ramirez A. Genetic association study of the P-type ATPase ATP13A2 in late-onset Parkinson’s disease. Mov Disord 2008;3:429-433.