Boris Rogelj

Academic achievements

Associate professor2013

Faculty of Pharmacy, University of Ljubljana, Slovenia

PhD1999

Interfaculty MSc and PhD Study of Biochemistry and Molecular Biology, University of Ljubljana, Slovenia

BSc1995

Dept. of Biology, Biotechnical Faculty, University of Ljubljana, Slovenia

Employment history

Research associate/Group leaderJan/2012-present

Dept. of Biotechnology, Jožef Stefan Institute, Ljubljana, Slovenia

Head of researchJan/2012-present

Biomedical Research Institute BRIS, Ljubljana, Slovenia

Senior research associateOct/2007-Dec/2011

Department of Clinical Neuroscience, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King’s College London, London, UK

Senior postdoctoral researcher Oct/2003-Sep/2007

Department of Neuroscience, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King’s College London, London, UK

Postdoctoral research fellow Sep/2000-Aug/2003

Dept. of Anatomy and Developmental Biology and Wolfson Institute for Biomedical Research, UniversityCollegeLondon, London, UK

Postdoctoral scientist Nov/1999-Sep/2000

Dept. of Biochemistry and Mol. Biology, Jozef Stefan Institute, Ljubljana, Slovenia

Junior researcherNov/1995-Nov/1999

Dept. of Biochemistry and Mol. Biology, Jozef Stefan Institute, Ljubljana, Sloveniaand Centre for Plant Breeding and Reproduction Research (CPRO-DLO), Wageningen, The Netherlands

During the last two years of my PhD I was a visiting junior researcher in CPRO-DLO.

Professional achievements

Proteins TDP-43 and FUS are major contributing factors in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We identified neighbouring mutations in a highly conserved region of TDP-43 and FUS in sporadic and familial ALS cases. Furthermore we have observed changes in degradation and location of both proteins in temporal lobe tissues in post-mortem tissues of patients with FTD. They are both predominantly nuclear proteins that are implicated in processing and transport of RNA. We have also characterized their RNA-binding properties as well as shown disease relevance of their nuclear transport.

We discovered that p62 is a major marker for ALS/FTLD associated with newly discovered hexanucleotide repeat mutation in C9orf72 gene and shown that the hexanucleotide repeat RNA sequesters hnRNPH in neurons. In addition, we have neuropathologically characterised optineurin in the context of ALS and FTLD and in a global analysis of alternative splicing changes in aging and neurodegeneration we discovered some correlations between the two processes.

Teaching experience

Lecturing

  • Lectures in Human Molecular Genetics at MSc Biochemistry course (2013-present), University of Ljubljana, Slovenia.
  • Lectures to students at MSc Neuroscience and MSc Clinical Neuroscience course (2008-2011).Institute of Psychiatry, King’s College London
  • Visiting lectures on Proteomics to the undergraduate students at the Faculty of Pharmacy and post-graduate students ofFaculty of Biotechnology (2001-2005), University of Ljubljana, Slovenia.
  • Host presenter during annual Alzheimer’s Open Day and lay and student group visits. Institute of Psychiatry, King’s College London.

Supervison

  • Current PhD supervisor of three students.Jozef Stefan Institute, Ljubljana, Slovenia.
  • MSc supervisor of three students.Institute of Psychiatry, King’s College London, UK.
  • MSc co-supervisor of one student.University College London, UK.
  • BSc co-supervisor of two students.

Management experience

  • Management of fiveresearch and three PhD grantsfrom Slovenian Research Agency.
  • Head of research in BRIS
  • Board member of SiNAPSa - Slovenian Neuroscience Society
  • Management of projects in Neurogenetics group, Department of Clinical Neuroscience, Institute of Psychiatry, King’s College London, London, UK

Grants and Funding

Current as PI:

  • Dysregulation of TDP-43 expression in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Slovenian Research Agency; 2013-2016
  • Pathogenic mechanism of the C9orf72 expanded hexanucleotide repeat mutation in neurodegeneration. Slovenian Research Agency; 2014-2017
  • PhD studentship: Slovenian Research Agency; 2014-2018
  • PhD studentship: Slovenian Research Agency; 2012-2016

Publications

Note: *first or shared first authorship; + last or shared last authorship

  1. +Štalekar M, Yin X, Rebolj K, Darovic S, Troakes C, Mayr M, Shaw CE, Rogelj B, 2015,Proteomic analyses reveal that loss of TDP-43 affects RNA processing and intracellular transport.Neuroscience, 293:157-70.
  2. Vrabec K, Koritnik B, Leonardis L, Dolenc Grošelj L, Zidar J, Smith B, Vance C, Shaw CE,Rogelj B, Glavač D, Ravnik-Glavač M, 2015,Genetic analysis of amyotrophic lateral sclerosis in the Slovenian population.Neurobiology of aging, 36:1601
  3. +Šket P, Pohleven J, Kovanda A, Štalekar M, Župunski V, Zalar M, Plavec J, Rogelj B, 2015, Characterization of DNA G-quadruplex species forming from C9ORF72 G4C2 expanded repeats associated with amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Neurobiology of aging, 36:1091-6
  4. Lee YB, Rogelj B, Shaw CE, 2014, A serum microRNA signature for amyotrophic lateral sclerosis reveals convergent RNA processing defects and identifies presymptomatic mutation carriers.Brain, 137:2875-6.
  5. +Bratkovič T, Rogelj B, 2014,The many faces of small nucleolar RNAs. BBA - Gene Regulatory Mechanisms, 1839:438-43.
  6. +Vatovec S, Kovanda A, Rogelj B, 2014,Unconventional features of C9ORF72 expanded repeat in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Neurobiology of Ageing, 35:2421.e1-2421.e12.
  7. +Kovanda A, Režen T, Rogelj B, 2014,MicroRNA in skeletal muscle development, growth, atrophy and disease. WIREs RNA, 5:509-25.
  8. Nishimura AL, Shum C, Scotter EL, Abdelgany A, Sardone V, Wright J, Lee YB, Chen HJ, Bilican B, Carrasco M, Maniatis T, Chandran S, Rogelj B, Gallo JM, Shaw CE, 2014,Allele-specific knockdown of ALS-associated mutant TDP-43 in neural stem cells derived from induced pluripotent stem cells PLOS One, 9:e91269.
  9. Scotter EL, Vance C, Nishimura AL, Lee YB, Chen HJ, Urwin H, Sardone V, Mitchell JC, Rogelj B, Rubinsztein DC, Shaw CE, 2014, Differential roles of the ubiquitin proteasome system (UPS) and autophagy in the clearance of soluble and aggregated TDP-43 species. Journal of Cell Science,127:1263-78.
  10. +Režen T, Kovanda A, Eiken O, Mekjavic IB, Rogelj B. 2014, Expression changes in human skeletal muscle miRNAs following 10 days of bed rest in young healthy males. Acta Physiologica (Oxf),210:655-666.
  11. Lee YB, Chen HJ, Peres JN, Gomez-Deza J, Attig J, Stalekar M, Troakes C, Nishimura AL, Scotter EL, Vance C, Adachi Y, Sardone V, Miller JW, Smith BN, Gallo JM, Ule J, Hirth F, Rogelj B, Houart C, Shaw CE. 2013, Hexanucleotide repeats in ALS/FTD form length-dependent RNA foci, sequester RNA binding proteins, and are neurotoxic. Cell Reports,5:1178-1186.
  12. +Vance C, Scotter EL, Nishimura AL, Troakes C, Mitchell JC, Kathe C, Urwin H, Manser C, Miller CC, Hortobágyi T, Dragunow M, Rogelj B, Shaw CE. 2013,ALS mutant FUS disrupts nuclear localization and sequesters wild-type FUS within cytoplasmic stress granules.Human Molecular Genetics,22:2676-2688.
  13. Mitchell JC, McGoldrick P, Vance C, Hortobagyi T, Sreedharan J, Rogelj B,Tudor EL, Smith BN, Klasen C, Miller CC, Cooper JD, Greensmith L, Shaw CE. 2013,Overexpression of human wild-type FUS causes progressive motor neuron degeneration in an age- and dose-dependent fashion. Acta Neuropathologica,125:273-288.
  14. +Troakes C, Hortobágyi T, Vance C, Al-Sarraj S, Rogelj B, Shaw CE. 2013, Transportin 1 co-localisation with FUS inclusions is not characteristic for ALS-FUS confirming disrupted nuclear import of mutant FUS and distinguishing it from FTLD-FUS. Neuropathology and Applied Neurobiology,39:553-561.
  15. Smith BN, Newhouse S, Shatunov A, Vance C, Topp S, Johnson L, Miller J, Lee Y, Troakes C, Scott KM, Jones A, Gray I, Wright J, Hortobágyi T, Al-Sarraj S, Rogelj B, Powell J, Lupton M, Lovestone S, Sapp PC, Weber M, Nestor PJ, Schelhaas HJ, Asbroek AA, Silani V, Gellera C, Taroni F, Ticozzi N, Van den Berg L, Veldink J, Van Damme P, Robberecht W, Shaw PJ, Kirby J, Pall H, Morrison KE, Morris A, de Belleroche J, Vianney de Jong JM, Baas F, Andersen PM, Landers J, Brown RH Jr, Weale ME, Al-Chalabi A, Shaw CE, 2013, The C9ORF72 expansion mutation is a common cause of ALS+/-FTD in Europe and has a single founder. European Journal of Human Genetics, 21:102-108.
  16. *Rogelj B, Easton LE, Bogu GK, Stanton LW, Rot G, Curk T, Zupan B, Sugimoto Y, Modic M, Haberman N, Tollervey J, Fujii R, Takumi T, Shaw CE, Ule J. 2012, Widespread binding of FUS along nascent RNA regulates alternative splicing in the brain. Scientific Reports, 2:603.
  17. Troakes C, Maekawa S, Wijesekera L, Rogelj B, Siklós L, Bell C, Smith B, Newhouse S, Vance C, Johnson L, Hortobágyi T, Shatunov A, Al-Chalabi A, Leigh N, Shaw CE, King A and Al-Sarraj S, 2012, MND/ALS with excess p62 pathology - a TDP-43 proteinopathy subtype exhibiting distinctive shared pathology yet genetic variability. Neuropathology, 32:505-514.
  18. +Bratkovic T, Glavan G, Strukelj B, Zivin M and Rogelj B, 2012, Exploiting microRNAs for cell engineering and therapy.Biotechnology Advances, 30:753-765.
  19. Al-Sarraj S, King A, Troakes C, Smith B, Makawa S, Bodi I, Rogelj B, Al-Chalabi A, Hortobagyi T and Shaw CE, 2011, 62 positive, TDP-43 negative, neuronal cytoplasmic and intranuclear inclusions in the cerebellum and hippocampus define the pathology of C9orf72 linked FTLD and ALS, Acta Neuropathologica, 122:691-702.
  20. +Bratkovic T and Rogelj B, 2011, Biology and applications of small nucleolar RNAs. Cellular and Molecular Life Sciences, 68:3843-3851.
  21. Tollervey JR, Wang Z, Hortobágyi T, Witten JT, Zarnack K, Kayikci M, Clark TA, Schweitzer AC, Rot G, Curk T, Zupan B, Rogelj B, Shaw CE andUle J, 2011, Analysis of alternative splicing associated with aging and neurodegeneration in the human brain. Genome Biology, 21:1572-1582.
  22. *Tollervey JR, Curk T, Rogelj B, Briese M, Cereda M, Kayikci M, König J,Hortobágyi T, Nishimura AL, Zupunski V, Patani R, Chandran S, Rot G, Zupan B,Shaw CE and Ule J, 2011, Characterizing the RNA targets and position-dependent splicingregulation by TDP-43. Nature Neuroscience,14:452-458.
  23. Hortobágyi T, Troakes C, Nishimura AL, Vance C, van Swieten JC, Seelaar H,King A, Al-Sarraj S, Rogelj B and Shaw CE,2011, Optineurin inclusions occur in a minorityof TDP-43 positive ALS and FTLD-TDP cases and are rarely observed in otherneurodegenerative disorders. Acta Neuropathologica,121:519-527.
  24. +Nishimura AL,Župunski V, Troakes C, Kathe C, Fratta P, Howell M, Gallo J-M, Hortobágyi T, Shaw CE and Rogelj B, 2010, Nuclear import impairment causes cytoplasmic TDP-43 accumulation and is associated with frontotemporal lobar degeneration, Brain, 133:1763-1771.
  25. Mitchell JC, Perkinton MS, Yates DM, Lau KF, Rogelj B, Miller CC and McLoughlin DM, 2010, Expression of the neuronal adaptor protein X11α protects against memory dysfunction in a transgenic mouse model of Alzheimer’s disease.Journal of Alzheimer’s disease, 20:31-36.
  26. Mitchell JC, Ariff BB, Yates DM, Lau KF, Perkinton MS,Rogelj B, Stephenson JD, Miller CCandMcLoughlin DM, 2009, X11β rescues memory and long-term potentiation deficits in Alzheimer's disease APPswe Tg2576 mice.Human Molecular Genetics, 18, 4492-4500.
  27. *Vance C,Rogelj B, Hortobagyi T, De Vos KJ, Sreedharan J, Hu X, Wright P, Nishimura AL, Ganesalingam J, Tripathi V, Smith B, Ruddy D, Al-Saraj S, Al-Chalabi A, Leigh PN, Blair IP, Nicholson G, de Belleroche J, Gallo J-M, Miller CC and Shaw CE. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6.Science, 323:1208-1211.
  28. Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B, Ackerley S, Buratti E, Baralle F, Durnall JC, Williams KL, de Belleroche J, Mitchell JD, Leigh PN, Miller CC, Al-Chalabi A, Nicholson G, and Shaw CE, 2008, TDP-43 mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis. Science,319:1668-1672.
  29. Miller CCJ, McLoughlin DM, Lau KF, Tennant ME andRogelj B, 2006, The X11 proteins, Aβ production and Alzheimer’s disease. Trends in Neurosciences, 29:280-285.
  30. *Rogelj B, 2006, Brain Specific Small Nucleolar RNAs. Journal of Molecular Neuroscience, 28:103-110.
  31. *Rogelj B, Mitchell JC, Miller CCJ and McLoughlin DM, 2006, X11 family of adaptor proteins.Brain Research Reviews, 52:305-315.
  32. Sabotic J, Gaser D, Rogelj B, Gruden K, Strukelj B and Brzin J, 2006, Heterogeneity of the cysteine protease inhibitor Clitocypin gene family. Biological Chemistry, 387:1559-1566.
  33. Anzlovar S, Gruden K, Rogelj B, Strukelj B and Dermastia B, 2006, Linusitin-like protein from flax is encoded by an intronless gene. International Journal of Plant Sciences,167:231-238.
  34. Lee JH, Lau KF, Perkinton MS, Standen CL, Rogelj B, Falinska A, McLoughlin DM and Miller CC, 2004, The neuronal adaptor protein X11beta reduces Abeta levels and amyloid plaque formation in the brains of transgenic mice. Journal of Biological Chemistry,279:49099-49104.
  35. *Rogelj B andGiese KP, 2004, Brain specific small non-messenger RNAs. Reviews in the Neurosciences,15:185-198.
  36. *Rogelj B, Hartmann CE, Hunt SP, Yeo CH and Giese KP, 2003, Contextual fear conditioning regulates the expression of brain-specific small nucleolar RNAs in hippocampus. European Journal of Neuroscience,18:3089-3096.
  37. *Outchkourov NS, Rogelj B, Strukelj B and Jongsma MA, 2003, Expression of sea anemone equistatin in potato: effects of plant proteases on heterologous protein production. Plant Physiology,133:379-390.
  38. *Brzin J, Rogelj B,Popovic T, Ritonja A and Strukelj B, 2000, Isolation, characterisation and primary structure of clitocypin, a new inhibitor of cysteine proteinases from Clitocybe nebularis fruiting bodies. Journal of Biological Chemistry,275:20104-20109.
  39. *Rogelj B, Strukelj B, Bosch D and Jongsma MA, 2000, Expression and purification of equistatin in Pichia pastoris. Protein expression and purification,19:329-334.
  40. Strukelj B, Lenarcic B, Gruden K, Pungercar J, Rogelj B, Turk V, Bosch D and Jongsma MA, 2000, Equistatin, a protease inhibitor from the sea anemone Actinia equina, is composed of three structural and functional domains. Biochemical and Biophysical Research Communications, 269:732-736.
  41. *Rogelj B, Popovic T, Ritonja A, Strukelj B and Brzin J, 1998, Chelidocystatin, a novel phytocystatin from Chelidonium majus. Phytochemistry, 49:1645-1649.

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