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Sarah Tabrizi

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Sarah Joanna Tabrizi
FMedSci
Sarah Tabrizi in 2013
Born
London, UK
Alma materHeriot-Watt University
University of Edinburgh
University College London
Known forResearch into neurodegeneration, particularly Huntington's disease
SpouseMichael Nath
AwardsFellowship of the Academy of Medical Sciences, 2014
Scientific career
FieldsNeuroscience
InstitutionsUCL Institute of Neurology;
National Hospital for Neurology and Neurosurgery
ThesisMitochondrial dysfunction in the pathogenesis of neurodegeneration (2000)
Websitehdresearch.ucl.ac.uk

Sarah Joanna Tabrizi FMedSci is a British-Persian neurologist and neuroscientist in the field of neurodegeneration, particularly Huntington's disease. She is a Professor and Joint Head of the Department of Neurodegenerative Diseases[1] at the UCL Institute of Neurology; the founder and Director of the UCL Huntington's Disease Centre; a Principal Investigator at the UK Dementia Research Institute at UCL; and an Honorary Consultant Neurologist at the National Hospital for Neurology and Neurosurgery, Queen Square, London, where she established the Multidisciplinary Huntington's Disease Clinic.[2][3][4] The UCL Huntington’s Disease Centre was officially opened on 1 March 2017 by UCL President and Provost Professor Michael Arthur.[5]

Education and Career

Tabrizi graduated with a first-class degree in biochemistry from Heriot-Watt University in 1986 and an MB ChB from the University of Edinburgh in 1992, where she graduated with the Gold Medal (Ettles Scholar) for the most distinguished medical graduate.[2] She obtained a PhD at University College London in 2000.[6] During her time as a trainee neurologist at the National Hospital for Neurology and Neurosurgery (NHNN), Queen Square, Sarah worked for Professors Anita Harding and David Marsden, both of whom would make a lasting impression on her.[7] She undertook an MRC Clinical Training Fellowship PhD studying mitochondrial dysfunction in neurodegeneration with Tony Schapira and Gillian Bates from 1996-1999 then obtained a Department of Health National Clinician Scientist Fellowship at the UCL Institute of Neurology in 2002 to work with John Collinge and Charles Weissmann on prion cell biology. She was promoted to UCL Clinical Senior Lecturer and Honorary Consultant Neurologist in 2003, to Reader in 2007 and Full Professor in 2009.[8]

Research

Tabrizi is distinguished for her work on mechanisms of cellular neurodegeneration[9][10][11][12][13] and in particular Huntington's disease pathobiology, biomarkers, outcome measures and first in human clinical trials.[14][15] Amongst her achievements, she has identified key pathogenic mechanisms in cellular degeneration in prion disease,[16][17][18] identified a key role for the innate immune system in the pathogenesis of Huntington’s disease,[19] published the first assay of the mutant HD protein in human blood cells,[20] and designed and led two major, international, influential research initiatives, TRACK-HD and Track-On HD. To date these studies have yielded fundamental new insights into the preclinical phase of neurodegeneration in Huntington’s disease including identifying predictors of disease onset,[21][22][23][24][25][26][27] progression, evidence of brain compensation and plasticity and neurobiological changes occurring twenty years before predicted disease onset, and her work established a battery of clinical trial outcome measures.[28][21][22][23][24][29] Recently her work identified an important new genetic modifier of disease progression in Huntington’s disease, which has opened up new avenues of research into targeting DNA repair pathways as possible therapeutics for Huntington’s disease.[30][31]

Tabrizi gave a keynote presentation at the 2016 Google Zeitgeist Minds conference about the trial, and the prospect of gene silencing for neurodegenerative disease.[32] She was the lead Clinical Investigator for the first clinical trial of a 'gene silencing' or huntingtin-lowering antisense oligonucleotide (ASO) drug in Huntington's disease patients. The announcement of the ‘top line’ results from the Phase 1b/2a safety trial in December 2017 received widespread national and international media coverage and was covered in features by BBC News,[33] Guardian[34] and Nature.[35] In May 2019 the full results were published in The New England Journal of Medicine.[36][37]

The potential of antisense oligonucleotides to treat neurodegenerative diseases was reviewed by Tabrizi in Science in 2020.[38] Tabrizi is currently working on several different approaches to treat Huntington’s disease, including testing novel ASOs targeting mismatch repair to slow CAG repeat expansion and new gene therapy approaches targeting the mutant HD gene. More recently Tabrizi published the Huntington’s Disease Young Adult Study (HD-YAS) studying premanifest HD gene carriers approximately 24 years from predicted onset of clinical symptoms using advanced neuroimaging, detailed cognitive testing and biofluid collection.[39] The cohort did not show any clinically meaningful functional impairment, yet there was evidence of elevated levels of neurofilament light protein, suggestive of very early neuronal damage, in those closest to expected symptom onset. HD-YAS will provide critical information on the very earliest signs of neurodegeneration, identifying a time at which a therapy could potentially be introduced to delay or even ultimately prevent the onset of clinical symptoms in HD.[39] This approach has implications beyond HD, providing a model for disease prevention in neurodegeneration and this work continues to be of major interest in the Tabrizi lab.[40]

In 2017 Tabrizi was the subject of a profile article in The Lancet Neurology.[41]

As of November 2020, Tabrizi had authored over 300 publications, with over 24,000 citations for her research.[42]

Awards and honours

Personal life

Tabrizi lives in London with her husband, the author Michael Nath.[6]

References

  1. ^ "Department of Neurodegenerative Disease". UCL Institute of Neurology.
  2. ^ a b "Iris View Profile". IRIS - UCL. Retrieved 5 May 2016.
  3. ^ "UCL Huntington's Disease Research". hdresearch.ucl.ac.uk.
  4. ^ "Prof Sarah Tabrizi". www.uclh.nhs.uk.
  5. ^ "The UCL Huntington's Disease Centre opens".
  6. ^ a b c "Who's Who 2016 - Tabrizi, Prof. Sarah Joanna". Who's Who 2016. Retrieved 6 May 2016.
  7. ^ Shetty, Priya (2012). "Sarah Tabrizi: Tracking Huntington's disease". The Lancet. 379 (9831): 2043. doi:10.1016/S0140-6736(12)60884-8. PMID 22656876. S2CID 40222846.
  8. ^ "Professor Sarah J Tabrizi". UCL Iris.
  9. ^ Deriziotis, Pelagia; André, Ralph; Smith, David M; Goold, Rob; Kinghorn, Kerri J; Kristiansen, Mark; Nathan, James A; Rosenzweig, Rina; Krutauz, Dasha; Glickman, Michael H; Collinge, John; Goldberg, Alfred L; Tabrizi, Sarah J (8 July 2011). "Misfolded PrP impairs the UPS by interaction with the 20S proteasome and inhibition of substrate entry". The EMBO Journal. 30 (15): 3065–3077. doi:10.1038/emboj.2011.224. PMC 3160194. PMID 21743439.
  10. ^ Kristiansen, Mark; Messenger, Marcus J.; Klöhn, Peter-Christian; Brandner, Sebastian; Wadsworth, Jonathan D. F.; Collinge, John; Tabrizi, Sarah J. (18 November 2005). "Disease-related Prion Protein Forms Aggresomes in Neuronal Cells Leading to Caspase Activation and Apoptosis". Journal of Biological Chemistry. 280 (46): 38851–38861. doi:10.1074/jbc.M506600200. PMID 16157591.
  11. ^ Kristiansen, Mark; Deriziotis, Pelagia; Dimcheff, Derek E.; Jackson, Graham S.; Ovaa, Huib; Naumann, Heike; Clarke, Anthony R.; van Leeuwen, Fijs W.B.; Menéndez-Benito, Victoria; Dantuma, Nico P.; Portis, John L.; Collinge, John; Tabrizi, Sarah J. (April 2007). "Disease-Associated Prion Protein Oligomers Inhibit the 26S Proteasome". Molecular Cell. 26 (2): 175–188. doi:10.1016/j.molcel.2007.04.001. hdl:11858/00-001M-0000-0012-2650-5. PMID 17466621.
  12. ^ Goold, R.; Rabbanian, S.; Sutton, L.; Andre, R.; Arora, P.; Moonga, J.; Clarke, A.R.; Schiavo, G.; Jat, P.; Collinge, J.; Tabrizi, S.J. (19 April 2011). "Rapid cell-surface prion protein conversion revealed using a novel cell system". Nature Communications. 2 (1): 281–. Bibcode:2011NatCo...2..281G. doi:10.1038/ncomms1282. PMC 3104518. PMID 21505437.
  13. ^ McKinnon, Chris; Goold, Rob; Andre, Ralph; Devoy, Anny; Ortega, Zaira; Moonga, Julie; Linehan, Jacqueline M.; Brandner, Sebastian; Lucas, José J.; Collinge, John; Tabrizi, Sarah J. (8 December 2015). "Prion-mediated neurodegeneration is associated with early impairment of the ubiquitin–proteasome system". Acta Neuropathologica. 131 (3): 411–425. doi:10.1007/s00401-015-1508-y. PMC 4752964. PMID 26646779.
  14. ^ Shetty, Priya (2012). "Sarah Tabrizi: Tracking Huntington's disease". The Lancet. 379 (9831): 2043. doi:10.1016/S0140-6736(12)60884-8. PMID 22656876. S2CID 40222846.
  15. ^ Mohammadi, Dara (July 2015). "Fast-forwarding treatment for neurodegenerative disorders". The Lancet Neurology. 14 (7): 687–688. doi:10.1016/S1474-4422(15)00110-6. PMID 26067120.
  16. ^ Deriziotis, Pelagia; André, Ralph; Smith, David M; Goold, Rob; Kinghorn, Kerri J; Kristiansen, Mark; Nathan, James A; Rosenzweig, Rina; Krutauz, Dasha; Glickman, Michael H; Collinge, John (2011-07-08). "Misfolded PrP impairs the UPS by interaction with the 20S proteasome and inhibition of substrate entry". The EMBO Journal. 30 (15): 3065–3077. doi:10.1038/emboj.2011.224. ISSN 0261-4189. PMC 3160194. PMID 21743439.
  17. ^ Kristiansen, Mark; Deriziotis, Pelagia; Dimcheff, Derek E.; Jackson, Graham S.; Ovaa, Huib; Naumann, Heike; Clarke, Anthony R.; van Leeuwen, Fijs W.B.; Menéndez-Benito, Victoria; Dantuma, Nico P.; Portis, John L. (April 2007). "Disease-Associated Prion Protein Oligomers Inhibit the 26S Proteasome". Molecular Cell. 26 (2): 175–188. doi:10.1016/j.molcel.2007.04.001. hdl:11858/00-001M-0000-0012-2650-5. PMID 17466621.
  18. ^ Kristiansen, Mark; Messenger, Marcus J.; Klöhn, Peter-Christian; Brandner, Sebastian; Wadsworth, Jonathan D. F.; Collinge, John; Tabrizi, Sarah J. (2005-11-18). "Disease-related Prion Protein Forms Aggresomes in Neuronal Cells Leading to Caspase Activation and Apoptosis". Journal of Biological Chemistry. 280 (46): 38851–38861. doi:10.1074/jbc.M506600200. ISSN 0021-9258. PMID 16157591.
  19. ^ Björkqvist, Maria; Wild, Edward J; Thiele, Jenny; Silvestroni, Aurelio; Andre, Ralph; Lahiri, Nayana; Raibon, Elsa; Lee, Richard V; Benn, Caroline L; Soulet, Denis; Magnusson, Anna; Woodman, Ben; Landles, Christian; Pouladi, Mahmoud A; Hayden, Michael R; Khalili-Shirazi, Azadeh; Lowdell, Mark W; Brundin, Patrik; Bates, Gillian P; Leavitt, Blair R; Möller, Thomas; Tabrizi, Sarah J (2008). "A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease". The Journal of Experimental Medicine. 205 (8): 1869–77. doi:10.1084/jem.20080178. PMC 2525598. PMID 18625748.
  20. ^ Weiss, Andreas; Träger, Ulrike; Wild, Edward J; Grueninger, Stephan; Farmer, Ruth; Landles, Christian; Scahill, Rachael I; Lahiri, Nayana; Haider, Salman; MacDonald, Douglas; Frost, Chris; Bates, Gillian P; Bilbe, Graeme; Kuhn, Rainer; Andre, Ralph; Tabrizi, Sarah J (2012). "Mutant huntingtin fragmentation in immune cells tracks Huntington's disease progression". Journal of Clinical Investigation. 122 (10): 3731–6. doi:10.1172/jci64565. PMC 3461928. PMID 22996692.
  21. ^ a b Tabrizi, Sarah J; Langbehn, Douglas R; Leavitt, Blair R; Roos, Raymund AC; Durr, Alexandra; Craufurd, David; Kennard, Christopher; Hicks, Stephen L; Fox, Nick C; Scahill, Rachael I; Borowsky, Beth; Tobin, Allan J; Rosas, H Diana; Johnson, Hans; Reilmann, Ralf; Landwehrmeyer, Bernhard; Stout, Julie C (2009). "Biological and clinical manifestations of Huntington's disease in the longitudinal TRACK-HD study: Cross-sectional analysis of baseline data". The Lancet Neurology. 8 (9): 791–801. doi:10.1016/s1474-4422(09)70170-x. PMC 3725974. PMID 19646924.
  22. ^ a b Tabrizi, Sarah J; Scahill, Rachael I; Durr, Alexandra; Roos, Raymund AC; Leavitt, Blair R; Jones, Rebecca; Landwehrmeyer, G Bernhard; Fox, Nick C; Johnson, Hans; Hicks, Stephen L; Kennard, Christopher; Craufurd, David; Frost, Chris; Langbehn, Douglas R; Reilmann, Ralf; Stout, Julie C; TRACK-HD Investigators (2011). "Biological and clinical changes in premanifest and early stage Huntington's disease in the TRACK-HD study: The 12-month longitudinal analysis". The Lancet Neurology. 10 (1): 31–42. doi:10.1016/s1474-4422(10)70276-3. PMID 21130037. S2CID 2602096.
  23. ^ a b Tabrizi, Sarah J; Reilmann, Ralf; Roos, Raymund AC; Durr, Alexandra; Leavitt, Blair; Owen, Gail; Jones, Rebecca; Johnson, Hans; Craufurd, David; Hicks, Stephen L; Kennard, Christopher; Landwehrmeyer, Bernhard; Stout, Julie C; Borowsky, Beth; Scahill, Rachael I; Frost, Chris; Langbehn, Douglas R; TRACK-HD investigators (2012). "Potential endpoints for clinical trials in premanifest and early Huntington's disease in the TRACK-HD study: Analysis of 24 month observational data". The Lancet Neurology. 11 (1): 42–53. doi:10.1016/s1474-4422(11)70263-0. PMID 22137354. S2CID 34929053.
  24. ^ a b Tabrizi, Sarah J; Scahill, Rachael I; Owen, Gail; Durr, Alexandra; Leavitt, Blair R; Roos, Raymund A; Borowsky, Beth; Landwehrmeyer, Bernhard; Frost, Chris; Johnson, Hans; Craufurd, David; Reilmann, Ralf; Stout, Julie C; Langbehn, Douglas R (2013). "Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington's disease in the TRACK-HD study: Analysis of 36-month observational data". The Lancet Neurology. 12 (7): 637–49. doi:10.1016/s1474-4422(13)70088-7. PMID 23664844. S2CID 12204298.
  25. ^ Klöppel, Stefan; Gregory, Sarah; Scheller, Elisa; Minkova, Lora; Razi, Adeel; Durr, Alexandra; Roos, Raymund A.C; Leavitt, Blair R; Papoutsi, Marina; Landwehrmeyer, G. Bernhard; Reilmann, Ralf; Borowsky, Beth; Johnson, Hans; Mills, James A; Owen, Gail; Stout, Julie; Scahill, Rachael I; Long, Jeffrey D; Rees, Geraint; Tabrizi, Sarah J (2015). "Compensation in Preclinical Huntington's Disease: Evidence from the Track-On HD Study". EBioMedicine. 2 (10): 1420–9. doi:10.1016/j.ebiom.2015.08.002. PMC 4634199. PMID 26629536.
  26. ^ Gregory, Sarah; Long, Jeffrey D; Klöppel, Stefan; Razi, Adeel; Scheller, Elisa; Minkova, Lora; Papoutsi, Marina; Mills, James A; Durr, Alexandra; Leavitt, Blair R; Roos, Raymund A. C; Stout, Julie C; Scahill, Rachael I; Langbehn, Douglas R; Tabrizi, Sarah J; Rees, Geraint (2017). "Operationalizing compensation over time in neurodegenerative disease". Brain. 140 (4): 1158–1165. doi:10.1093/brain/awx022. PMC 5382953. PMID 28334888.
  27. ^ Gregory, Sarah; Long, Jeffrey D; Klöppel, Stefan; Razi, Adeel; Scheller, Elisa; Minkova, Lora; Johnson, Eileanoir B; Durr, Alexandra; Roos, Raymund A C; Leavitt, Blair R; Mills, James A; Stout, Julie C; Scahill, Rachael I; Tabrizi, Sarah J; Rees, Geraint; Coleman, A; Decolongon, J; Fan, M; Koren, T; Leavitt, B; Durr, A; Jauffret, C; Justo, D; Lehericy, S; Nigaud, K; Valabrègue, R; Roos, R; Hart, E P 't; Schoonderbeek, A; et al. (2018). "Testing a longitudinal compensation model in premanifest Huntington's disease". Brain. 141 (7): 2156–2166. doi:10.1093/brain/awy122. PMC 6022638. PMID 29788038.
  28. ^ Shetty, Priya (2012). "Sarah Tabrizi: Tracking Huntington's disease". The Lancet. 379 (9831): 2043. doi:10.1016/s0140-6736(12)60884-8. PMID 22656876. S2CID 40222846.
  29. ^ Arney, Kat (2018). "Improved metrics for Huntington's disease trials". Nature. 557 (7707): S46–S47. Bibcode:2018Natur.557S..46A. doi:10.1038/d41586-018-05179-w. PMID 29844554.
  30. ^ Moss, Davina J Hensman; Pardiñas, Antonio F; Langbehn, Douglas; Lo, Kitty; Leavitt, Blair R; Roos, Raymund; Durr, Alexandra; Mead, Simon; Holmans, Peter; Jones, Lesley; Tabrizi, Sarah J; Coleman, A; Santos, R Dar; Decolongon, J; Sturrock, A; Bardinet, E; Ret, C Jauff; Justo, D; Lehericy, S; Marelli, C; Nigaud, K; Valabrègue, R; Van Den Bogaard, SJA; Dumas, E M; Van Der Grond, J; t'Hart, EP; Jurgens, C; Witjes-Ane, M-N; Arran, N; et al. (2017). "Identification of genetic variants associated with Huntington's disease progression: A genome-wide association study" (PDF). The Lancet Neurology. 16 (9): 701–711. doi:10.1016/s1474-4422(17)30161-8. PMID 28642124. S2CID 588163.
  31. ^ Flower, Michael; Lomeikaite, Vilija; Ciosi, Marc; Cumming, Sarah; Morales, Fernando; Lo, Kitty; Hensman Moss, Davina; Jones, Lesley; Holmans, Peter; Monckton, Darren G.; Tabrizi, Sarah J. (2019-07-01). "MSH3 modifies somatic instability and disease severity in Huntington's and myotonic dystrophy type 1". Brain. 142 (7): 1876–1886. doi:10.1093/brain/awz115. ISSN 0006-8950. PMC 6598626. PMID 31216018.
  32. ^ Tabrizi, Sarah (May 2016). "The Human Revolution". zeitgeistminds.com.
  33. ^ Gallagher, James (11 December 2017). "Huntington's breakthrough may stop disease". bbc.co.uk.
  34. ^ Devlin, Hannah (11 December 2017). "Excitement as trial shows Huntington's drug could slow progress of disease". guardian.com.
  35. ^ Drew, Liam (2018). "How the gene behind Huntington's disease could be neutralized". Nature. 557 (7707): S39–S41. Bibcode:2018Natur.557S..39D. doi:10.1038/d41586-018-05176-z. PMID 29844556.
  36. ^ Tabrizi, Sarah J.; Leavitt, Blair R.; Landwehrmeyer, G. Bernhard; Wild, Edward J.; Saft, Carsten; Barker, Roger A.; Blair, Nick F.; Craufurd, David; Priller, Josef (2019-05-06). "Targeting Huntingtin Expression in Patients with Huntington's Disease" (PDF). New England Journal of Medicine. 380 (24): 2307–2316. doi:10.1056/NEJMoa1900907. ISSN 0028-4793. PMID 31059641.
  37. ^ "Full Results from Huntingtin Lowering Antisense Oligonucleotides Trial now published". UCL Queen Square Institute of Neurology.
  38. ^ Leavitt, Blair R.; Tabrizi, Sarah J. (2020-03-27). "Antisense oligonucleotides for neurodegeneration". Science. 367 (6485): 1428–1429. Bibcode:2020Sci...367.1428L. doi:10.1126/science.aba4624. ISSN 0036-8075. PMID 32217715. S2CID 214671177.
  39. ^ a b Scahill, Rachael I; Zeun, Paul; Osborne-Crowley, Katherine; Johnson, Eileanoir B; Gregory, Sarah; Parker, Christopher; Lowe, Jessica; Nair, Akshay; O'Callaghan, Claire; Langley, Christelle; Papoutsi, Marina (June 2020). "Biological and clinical characteristics of gene carriers far from predicted onset in the Huntington's disease Young Adult Study (HD-YAS): a cross-sectional analysis". The Lancet Neurology. 19 (6): 502–512. doi:10.1016/S1474-4422(20)30143-5. PMC 7254065. PMID 32470422.
  40. ^ "Study provides 'vital insights' into best time to treat Huntington's disease". ITV News. 2020-05-26. Retrieved 2020-11-30.
  41. ^ Burton, Adrian (2018). "Sarah Tabrizi: Timed to perfection". The Lancet Neurology. 17 (2): 117. doi:10.1016/s1474-4422(17)30303-4. PMID 28916420.
  42. ^ "Sarah J Tabrizi - Google Scholar Citations". scholar.google.co.uk.
  43. ^ UCL (2019-11-05). "Co-Heads of Department awarded Alexander Morison medal in successive years". UCL Queen Square Institute of Neurology. Retrieved 2019-11-06.
  44. ^ UCL (2019-10-31). "Professor Sarah Tabrizi receives Yahr award at World Congress of Neurology 2019". UCL Queen Square Institute of Neurology. Retrieved 2019-11-06.
  45. ^ "Professor Sarah Tabrizi, UCL Queen Square Institute of Neurology, receives the 2018 Cotzias Award". UCL News.
  46. ^ Tabrizi, Sarah. "The NHS at 70 years". ucl.ac.uk.
  47. ^ "UCL News". ucl.ac.uk.
  48. ^ "Fellow - Academy of Medical Sciences". www.acmedsci.ac.uk.
  49. ^ "Governance - Wellcome". wellcome.ac.uk.
  50. ^ "Journal of Huntington's Disease". www.iospress.nl. Retrieved 13 June 2016.
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