Hilal Lashuel
Associate Professor
hilal.lashuel@epfl.ch +41 21 693 96 91 http://lashuel-lab.epfl.ch
Citizenship: USA
Birth date: 15.01.1973
EPFL SV BMI LMNN
AI 2151 (Bâtiment AI)
Station 19
1015 Lausanne
+41 21 693 96 91
+41 21 693 07 92
Office:
AI 2151
EPFL
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Web site: Web site: https://lashuel-lab.epfl.ch/
Web site: Web site: https://sv.epfl.ch/education
EPFL > VPA-AVP-CP > CIME > CIME-CD
Mission
To elucidate the molecular mechanisms underlying neurodegeneration in Alzheimer's , Parkinson's and Huntingtons disease and develop novel strategies to facilitate the diagnosis, prevention and treatment of these diseases.Current work
Current research in the Lashuel laboratory focuses on applying chemical, biophysical, structural and molecular biology approaches to understanding the molecular and structural basis of protein misfolding and self-assembly and the mechanisms by which these processes contribute to the physiological and pathogenic properties of specific proteins implicated in neurodegenerative diseases. Current research efforts cover the following topics: (1) Elucidating the molecular and cellular determinants underlying amyloid-? and ?-synuclein aggregation and toxicity in Alzheimers diseases and Parkinsons disease and related disorders. (2) Elucidating the structural basis of amyloid-associated toxicity by correlating the structural properties of defined aggregates in the amyloid pathway to their toxicity in primary neuronal cultures; (3) Developing innovative chemical approaches and novel tools to monitor and control protein folding/misfolding and self-assembly in vitro and in vivo with spatial and temporal resolution; (4) Understanding the role of post-translational modifications in the pathogenesis of neurodegenerative diseases; (5) Identifying and validating new therapeutic targets for treating Parkinsons disease; (6) Developing novel therapeutic strategies to treat neurodegenerative diseases based on modulation of protein aggregation and clearance.Biography
2012-2013 Visiting Professor, Standford University. Stanford School of Medicine 2011- Associate Professor of Life Sciences-Brain Mind Institute-EPFL Dir. Laboratory of Chemical Biology of Neurodegeneration 2005-2011 Assistant Professor of Life Sciences-Brain Mind Institute-EPFL Dir. Laboratory of Molecular Neurobiology and Neuroproteomics 2005-2008 Director- EPFL Proteomic Core Facility 2002-2004 Instructor of Neurology- Harvard Medical School and Brigham and Women's Hospital 2001-2002 Sabbatical Fellow- Laboratory for Drug Discovery in Neurodegeneration Harvard Medical School, 2001-2002 Post-doctoral Fellow- Center for Neurologic Diseases Harvard Medical School and Brigham and Women's Hospital Advisor- Prof. Peter T. Lansbury 2000-2001 Research Scientist, The Picower Institute for Medical Research, Great Neck New York 1994-2000 PhD Student; Texas A&M University and the Scripps Research Institute Advisor- Prof. Jeffery W. Kelly 1990-1994 B.S. City University of New York, Brooklyn College Dr. Hilal A. Lashuel received his B.Sc. degree in chemistry from the City University of New York in 1994 and completed his doctoral studies at Texas A&M University and the Scripps Research Institute in 2000. After obtaining his doctoral degree, he became a research fellow at the Picower Institute for Medical Research in Long Island New York. In 2001, he moved to Harvard Medical School and the Brigham and Women's Hospital as a research fellow in the Center for Neurologic Diseases and was later promoted to an instructor in neurology at Harvard Medical School. During his tenure (2001-2004) at Harvard Medical School his work focused on understanding the mechanisms of protein misfolding and fibrillogenesis and the role of these processes in the pathogenesis of Parkinson's and Alzheimer's disease. In 2005 Dr. Lashuel moved Switzerland to join the Brain Mind Institute at the Swiss Federal Institute of Technology Lausanne as a tenure-track assistant professor in neurosciences. Currently, Dr. Lashuel is an associate professor of life sciences and the director of the laboratory of molecular and chemical biology of neurodegeneration. (http://lashuel-lab.epfl.ch/). Research efforts in the Lashuels laboratory focus on understanding the molecular mechanisms of neurodegeneration and developing novel strategies to diagnose and treat neurodegenerative diseases such as Alzheimers and Parkinsons disease. Research in the Lashuel lab is funded by several international funding agencies and foundations, including the Swiss National Science Foundation, European FP7 program (Marie Curie and ERC grants), Human Science Frontiers, Strauss Foundation, Cure the Huntingtons disease foundation and Michael J Fox foundation and is supported by collaborations with pharmaceutical and biotech companies (http://lashuel-lab.epfl.ch/page-50538-en.html), Nestle, Merck-Serono, AC Immune and Johnson and Johnson. Dr. Lashuels research has resulted in the characterization of novel quaternary structure intermediates on the amyloid pathway, identification of potential therapeutic targets, and new hypotheses concerning the mechanisms of pathogenesis in Alzheimers disease, Parkinsons disease and related disorders. Dr. Lashuel scientific contribution to this field includes i) more than100 publications in major peer reviewed journals including Nature journals, Cell, PNAS, JBC, J. Neuroscience JACS, and Angewandtie Chemie; ii) three patents on novel strategies for preventing protein aggregation and treating autoimmune and inflammatory diseases; iii) more than 150 invited lectures since 2002 and more than 5500 citations (7800 citation-Google Scholar) since 1996. Dr. Lashuel has received several pre-doctoral and post-doctoral awards and fellowships and was the recipient of two prestigious awards given to young investigators; Human Science Frontiers young investigator research award and the European Research Council (ERC) starting independent researcher grant and the ERC proof of concept award (2013) These awards provide more than $2.5 Million to Dr. Lashuel to translate some of his ideas and projects into novel strategies for diagnosing and treating neurodegenerative diseases such as Alzheimers and Parkinsons disease. Dr. Lashuel has chaired and co-organized several international conferences and serves as an academic editor for PLoS ONE, an associate editor for frontiers of molecular neuroscience, member of the Editorial advisory board of ChemBioChem and ad hoc reviewer for several international scientific journals and funding agencies.Selected Publications
Complete List of Publications: http://www.ncbi.nlm.nih.gov/pubmed?term=lashuel Google Scholar Citations: http://scholar.google.com/citations?user=tDdAP4EAAAAJ&hl=en&oi=ao 1. Oueslati A, Schneider BL, Aebischer P, and Lashuel HA* PLK2 regulates selective autophagic clearance of a-synuclein and suppresses its toxicity 2013, Proceedings of the National Academy of Sciences USA, August, published ahead of print 2. Haj-Yahia M, Fauvet B, Herman-Badhinsky Y, Hejjaoui M, Bavikar SN, Vedhanarayanan K, Ciechanover A*, Lashuel HA* and Brik A*. Synthetic polyubiquitin alpha-synuclein reveals important insights into the roles of the ubiquitin chain in regulating its pathophysiology 2013, Proceedings of the National Academy of Sciences USA, Sep 16. [Epub ahead of print] 3. Fauvet B, Butterfield SM, Fuks J, Brik A, and Lashuel HA*, One-pot total chemical synthesis of alpha-synulein. Chem Commu (Camb), 2013, 49 (81), 9254 - 9256 4. Lashuel HA, Overk C, Ouelati A, and Masliah E ?-synuclein oliogmerizatoin in health and disease, Nature Rev. Neuroscience, 2013 Jan;14(1):38-48. 5. Wang Z and Lashuel HA* Discovery of a novel aggregation domain in the Huntingtin Protein: Implications for the mechanisms of Htt aggregation and toxicity, 2013, Angewandte Chemie, 2013 2013 Jan 7;52(2):562-7. 6. Shabek N, Herman-Bachinsky Y, Buchsbaum S, Lewinson O, Haj-Yahya M, Hejjaoui M, Lashuel HA, Sommer T, Brik A, Ceichanover A. The size of the proteasomal substrate determines whether its degradation will be mediated by Mono- or Polyubiquitination. Mol. Cell. 2012, 12;48(1):87-97 7. Hejjaoui M, Butterfield S, Fauvet B, Vercryusse F, Cun J, Dikiy I, Prudent M, Olschewski D, Zhang Y, Eliezer D., Lashuel HA* Chemical Biology of ?-synuclein: Elucidating the role of C-terminal post-translational modifications using protein semisynthetic strategies: Phosphorylation at Tyrosine 125, J. Amer. Chem. Soc, 2012. 21;134(11):5196-210. 8. Oueslati A, Paleologou KE, Schneider BL, Aebischer P., Lashuel HA* Mimicking phosphorylation at Serin87 inhibits the aggregation of human alpha-synuclein and protects against its toxicity in a rat model of Parkinsons disease, J. Neuroscience, 2012, 1;32(5):1536-44. 9. Fauvet B., Mebfo MK, Fares BM, Desobry C, Michael S, Ardah MT, Tsika E, Coune P, Eliezer D, Moore DJ, Schneider B, Aebischer P., El-agnaf OM, Masliah E, and Lashuel HA* Alpha-synuclein in the central nervous system, in mammalian cells, and produced by E. coli exists predominantly as a disorderd monomer, 2012, J. Biol. Chem, 287, 15345-15364 10. Jan A, Adolfsson O, Allaman I, Buccarello AL, Magistretti PJ, Pfeifer A, Muhs A, Lashuel HA*, A?42 neurotoxicity is mediated by ongoing nucleated polymerization process rather than by discrete A?42 species. J. Biol. Chem, 2011, 286(10):8585-96. 11. Hejjaoui H, Haj-Yahya M, Kumar KS, Brik A* and Lashuel HA* Towards elucidating the role of ubiquitination in the pathogenesis of Parkinsons disease using semisynthetic ubquitinated ?-synuclein. Angew Chem Int Ed, 2011, 10;50(2):405-9. 12. Conboy L, Varea E, Ouertatani-Sakouhi H, Calandra T, Lashuel HA, Sandi C. Essential role of macrophage migration inhibitory factor (MIF) on hippocampal neurogenesis, antidepressant effects and behavior. 2011, Mol. Psychiatry, 16(5):533-47. 13. Paleologou KE., Oueslati Abid, Kim H-Y, Lamberto GR., Rospigliosi CC., Schmid A., Chiappe D., Moniatte M., Eliezer D., Zweckstetter M., Masliah E. Lashuel HA*. Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions J. Neuroscience, 2010, 3;30(9):3184-98. 14. Mbefo MK, Paleologou KE, Boucharaba A, Oueslati A, Olschewski D, Schell H, Fournier M, Zweckstetter M., Kahle PJ, Masliah E Hirling H, and Lashuel HA*. Phosphorylation of synucleins (?, ? and ?) by members of the Polo Like family of Kinases, PLKs 1-4, 2010, J. Biol. Chem, 285(4):2807-22. 15. Allaman I., Gavillet M., Belanger M., Laroche T., Virtel D, Lashuel HA, Magistretti PJ. Beta-amyloid aggregates cause alteration of astrocytic metabolic phenotype: impact on neuronal viability, J. Neuroscience, 2010, 3;30(9):3326-38. 16. Jan A, Hartley DM and Lashuel HA*. Preparation and characterization of toxic A? intermediates for structural and functional studies in Alzheimers disease research. Nature Protocols, 2010;5(6):1186-209. 17. Butterfied SM and Lashuel HA*. Amyloidogenic protein-membrane interactions: mechanistic insights from model systems. Angewandte Chemie, 2010, 49, 5628-5654. 18. Ouertatani-Sakouhi H, El-Turk F, Fauvet F, Cho MK, Roger T, Dewor M, Bernhagen J, Calandra T, Zweckstetter M. Lashuel HA*. Identification and characterization of novel classes macrophage migration inhibitory factor (MIF) inhibitors with distinct mechanisms of action. J. Biol. Chem. 2010. 34, 26581-26598. 19. Paleologou KE., Schmid A., Rospigliosi CC, Kim H-Y, Lamberto GR., Fredenburg RA., Lansbury PT, Jr., , Fernandez CO., Eliezer D., Zweckstetter M., Lashuel HA*. Phosphorylation at Ser-129 but not the phosphomimics S129E/D inhibits the fibrillation of alpha-synuclein. J. Biol. Chem, 2008, 283:16895-905. 20. El-turk F., Michele C., Ouertatani-Sakouhi H., Zweckstetter, M., Leng L, Bucala R., Röthlisberger U., Lashuel HA*. The role of the carboxy terminal residues 104-114 in modulating the conformational flexibility and catalytic activity of Macrophage migration inhibitory factor (MIF). Biochemistry 2008, 47(40):10740-10756. 21. Jan A., Goekce Ol, Luthi-Carter R., and Lashuel HA*. The ratio of monomeric/ aggregated forms of A? (40&42) is an important determinant of A? aggregation and fibrillogenesis in Alzheimers diseases. J. Biol. Chem, 2008, 283(42):28176-89. 22. Lo Bianco C., Shorter J., Régulier E., Lashuel HA., Iwatsubo T., Lindquist S., Aebischer P. Hsp104 Antagonizes ?-Synuclein Aggregation and Reduces Dopaminergic Degeneration in a Rat Model of Parkinsons Disease. J. Clinc. Inv, 2008, 118, 3087-3098. 23. Arimon M., Grimminger V., Sanz F., Lashuel HA*. Hsp104 targets multiple intermediates on the amyloid pathway and suppresses the seeding capacity of fibrils and protofibrils of A?. J. Mol. Biol, 2008, 384(5):1157-1173. 24. Mimna R., Camus M-S., Schmid A., Tuchscherer G., Lashuel HA*, Mutter M*. Switch Peptides: Disruption of amyloid fibrils through controlled induction of ?-sheet to ?-helix transformation. Angewandte Chemie, 2007, 46, 2681-2684. 25. Lansbury PT* and Lashuel HA*. A century-old debate on protein aggregation and neurodegeneration enters the clinic. Nature, 2006, 443, 774-779. 26. Lashuel HA* and Lansbury PT*. "Are amyloid diseases caused by protein aggregates that mimic bacterial pore-forming toxins?" Quarterly Review of Biophysics. 2006, 39 (2), 1-35. 27. Nakagawa T, Futai K, Lashuel HA, Lo I, Okamoto K, Hayashi Y, Walz T, and Sheng M. EM Structure, Protein Dynamics and Synaptic Function of SAP97, and AMPA Receptor Scaffold Protein. Neuron, 2004, 28;44(3):453-467. 28. Lashuel HA, Hartley D, Petre B, Wall, Simon M, Walz T, Lansbury PT . Mixtures of wild-type and a pathogenic (E22G) form of A40 in vitro accumulate protofibrils, including amyloid pores. J. Mol. Biol. 2003, 332, 795-808. 29. Liu Y, Lashuel HA, Choi S, Xing X, Case A, Ni J, Yeh L, Cuny, GD, Stein RL, and Lansbury PT, Jr. A Class of Small Molecule UCH-L1 Inhibitors: Chemical Genetic Tools to Probe the Pathogenesis of Parkinsons Disease and Cancer. 2003, Chemistry & Biology. 2003, 10, 837-846. 30. Kheterpal I*, Lashuel HA*, Hartley DM, Walz T, Lansbury PT Jr., Wetzel R. A? protofibrils possess a stable core structure resistant to hydrogen exchange. Biochemistry. 2003, 42, 14092-14098. 31. Foguel D, Suarez MC, Ferrão-Gonzales AD, Porto TR, Palmieri L, Einsiedler C, Lashuel HA, Lansbury PT, Kelly JW, and Silva JL. Dissociation of Amyloid Fibrils of -Synuclein and Transthyretin by Pressure Reveals their Reversible Nature and the Formation of Water-Excluded Cavities. Proceeding of the National Academy of Science, U.S.A. 2003, 100, 9831-9836. 32. Lashuel HA, Hartley D, Petre B, Walz T, Lansbury PT. Neurodegenerative Disease, Amyloid Pores from Pathogenic Mutations. Nature. 2002, 418, 291-291. 33. Liu Y, Fallon L, Lashuel HA, Liu Z, Lansbury PT. The UCH-L1 Gene Encodes Two Opposing Enzymatic Activities that Affect alpha-Synuclein Degradation and Parkinson's Disease Susceptibility. Cell. 2002 ,111, 209-218. 34. Lashuel HA*, Hartley D, Balakhaneh D, Teichberg S, Callaway DE*. New Class of Inhibitors of Amyloid-? (A?) Fibril Formation: Implications for the Mechanism of Pathogenesis in Alzheimers disease. J. Biol. Chem. 2002, 277: 42881-42890. 35. Lashuel HA, Petre B, Wall, Simon M, Nowak RJ, Walz T, Lansbury PT. -Synuclein, Especially the Parkinsons Disease-Associated Mutants, Form Pore-like Annular and Tubular Protofibrils. J. Mol. Biol. 2002 , 322, 5, 1089-1102. 36. Wang, L, Lashuel HA, Walz, T. and Colon F. Serum Amyloid A Forms a Hexamer with a Central Channel. Proceeding of the National Academy of Science, 2002, 99, 15947-15952. 37. Lashuel HA, LaBrenz SR, Woo L, Kelly JW. A Peptidomimetic that forms Cables, Monolayers (or Bilayers) or Fibrils Depending on Solution Conditions: Implications For Material Science and Neurodegenerative Diseases. Journal of the American Chemical Society, 2000, 122, 22, 5262-5277. 38. Liu K, Cho HW, Lashuel HA, Kelly JW, Wemmer DE. A Glimpse of a Possible Amyloidogenic Intermediate of Transthyretin. Nature Structural Biology, 2000, 7, 754-757. 39. Lashuel HA, Wurth C, Woo L, Kelly JW. The Most Pathogenic Transthyretin FAP-Associated Variant, L55P, Forms Amyloid Fibrils Under Physiological and Acidic Conditions. Biochemistry, 1999, 38, 13560 - 13573. 40. Lashuel HA, Lai Z, Kelly JW. Characterization of the Transthyretin Acid Denaturation Pathway by Analytical Ultracentrifugation: Implications for wild type, V30M and L55P Amyloid Fibril Formation. Biochemistry. 1998, 37, 51, 17851-17864. 41. Hengst L, Lashuel HA, Reed SI. One Molecule of p21Kip1Is Sufficient to Inhibit One CdK/Cyclin Complex. Genes & Development. 1998, 12, 3882-3888. 42. Lai Z, McCulloch J, Lashuel HA, Kelly JW. GdnHCL Induced Denaturation and Refolding of Transthyretin Exhibits a Marked Hysteresis: Equilibria with High Kinetic Barriers. Biochemistry. 1997, 36, 33, 10230-10239. 43. Miroy GJ, Zhihong L, Lashuel HA, Peterson SA, Strang C, Kelly JW. Inhibiting Amyloid Fibril Formation via Protein Stabilization. Proceedings of the National Academy of Science. U.S.A. 1996, 93, 15051-1506.Patents
1. Miroy GJ, Kelly JW, Lai Z, Lashuel HA, Petterson SA. Treatment of amyloid disease using amyloidogenic protein-stabilizing compounds - used to treat a variety of amyloid diseases including Alzheimer's disease, mad cows disease etc.. WO9827972-A; WO9827972-A2; AU9857277-A 2. Lashuel HA, Callaway DE. Use of apomorphine derivative or its analogs for inhibition or reduction of amyloid beta fibril formation and for delaying onset of Alzheimers disease. WO2003053356-A; WO2003053356-A2; AU2002357911-A1; US2003187011-A1. 3. Lashuel HA and Hajer Ouertatani-Sakouhi. Method and Substances for inhibition of tautomerase activity of macrophage migration inhibitory factor (MIF). WO 2009/031545.Invited Talks
2013 5. Department of Neurology and Neurological Sciences Annual Retreat, Stanford University Jan, 2013. 6. Genentech, San Francisco, January 22nd, 2013. 7. International Conference on "Alpha-synuclein in Parkinson's disease and related neurodegenerative diseases: From Mechanisms to Therapeutic Strategies", March 1-3rd, 2013. 8. AD/PD Conference, Florence Italy, March 6-10th, 2013 9. Young Global Leaders Future Development Summit, March 17-19th, 2013 10. American Physical Society Annual Meeting, "Physics of Proteins II: Protein Association, Interaction, and Aggregation." Baltimore, USA, March 18-22nd, 2013 11. 5th Chemical protein synthesis (CPS) Meeting, Vienna, Austria, April 3-6th, 2013 12. CHDI's 8th Annual HD Therapeutics Conference - Venice, Italy, April 8-11, 2013 13. Neuroscience School of Advanced Studies, Protein Aggregation Spectrum Disorders, June 15-23, 2013 14. European Biophysical Society, Lisbon, Portugal, July 13-17th, 2013. 15. 2013 FASEB Summer Research Conference on Molecular Mechanisms and Physiological Consequences of Protein Aggregation. 16. MEFOPA & Neurasync Final Meeting September 19?21 2013, Rome 17. Stepping Stone Symposium, China, October 17-21, 2013 18. ?-Synuclein Summit organized by the Michael J Fox Foundation, Nov 7-8th, 2013 New York, USA 19. Bioeconomy Rome International Conference, Rome, No 25-26 20. 6th International Conference on Alzheimers Disease and Related Disorders in the Middle East, Istanbul, Turkey, October 23-24th, 2013 21. 4th Scandinavian Amyloid Symposium, Lund University, Nov 18-20, 2013, Lund, Sweden 22. Brain Forum, Dec 3-4th, 2013, Jeddah, Saudi Arabia 2012 23. MRC National Institute for Medical Research, London, UK, February 2nd, 2012 24. Department of Neurobiology, Reed Neurological Research Center, UCLA, LA, USA, March 2nd, 2012. 25. Neuroscience School of Advanced Studies, A course on Synucleinopathies, April 17-18th, 2012 26. 2nd Prato Conference on Pore Forming Proteins, Parto, Italy, April 18-20th, 2012 27. CECAM workshop about "Anchoring simulations to experiments: challenges for understanding and treating Alzheimer's disease", Paris, France, May 14-22nd, 2012 28. Jazan University Research Symposium, Jazan, Saudi Arabia, May 27-28th, 2012 29. Stepping Stone Symposia. First Conference on Cancer and Neurodegenerative diseases, Zurich, Switzerland, June 20-22nd, 2012 30. Department of Chemistry, Technische Universität München, Germany, June 26th, 2012 31. Neurasync training course, Max Plank Institute, Gottengen, Germany, June 26th, 2012 32. 2nd Gordon Research Conference Intrinsically Disordered Proteins, Vermont, USA. July 8 13, 2012. 33. 5th international Symposium on Macrophage Migration Inhibitory Factor (MIF), Louisville, KY, USA, Sept 13, 2012 34. '100 Years Lewy Bodies Where are we now?' a special symposium organized in the historical building of the Dept of Psychiatry in Munich, Germany, where Friedrich Jacob Heinrich Lewy discovered the Lewy Bodies 100 yrs. ago in 1912. Munich, Germany, September 15th, 2012. 35. Neuromodel Symposium, Kings College London School of Medicine, September 20-21st, 2012 36. School on Biological Physics, Rio de Janeiro, Brazil, September, 30- October 7th, 2012, 37. Post-Translational Modifications: Detection and Physiological Role, Granlibakken, Lake Tahoe, October 11-14, 2012 38. "Yemen in Transition: Challenges and Opportunities", Harvard University, USA, October 19-21, 2012 39. Scripps Research Institute La Jolla, San Diego, Nov 16th, 2012 40. SASTA-Arab League Conference, Cairo, Egypt, Dec 19-21st, 2012 41. TEDx Sanaá http://www.tedxsanaa.com/pages/ , Sanaá, Yemen, Dec 31st, 2012. 2011 42. Keynote speaker. University of Tokyo, Centre for Medical System Innovation (CMSI) annual symposium, Tokyo, Japan, Feb 22nd, 2011. 43. 4th international Symposium on Macrophage Migration Inhibitory Factor (MIF), New Haven, USA, May 11-14th, 2011 44. 10th Congress of the French Neuroscience Society, New experimental tools and therapies for Parkinsons disease, Marseille, France, May 25th, 2011 45. International Society of Neuroscience meeting From genes to pathogenesis: The evolving spectrum of synucleinopathies. Athens, Greece, Sep 4-6, 2011. 46. Faculty of Sciences, Jordan University of Science and Technolgoy, Jordan, Oct , 2011 47. King Abdullah University of Science and Technology, Saudi Arabia, Nov 27th, 2011. 2010 48. Boston Biomedical Research Institute, Cambridge, Boston, January 11th, 2010. 49. Alpha Synuclein Summit, Organized by Michael J. Fox Foundation, New York, USA, January 13-14, 2010. 50. Genentech Inc. San Francisco, CA, USA, January 15, 2010 51. Biophysics School on the Molecular Mechanisms of Neurodegeneration Molecular Mechanisms of Neurodegeneration Venice, Italy, January 25th, 2010. 52. Department of Biochemistry, University of Bologna, Italy, April 20-21st, 2010 53. Global Redesign Summit organized by the World Economic Forum and the foreign ministry of the state of Qatar. May 21-22nd, 2010. 54. Eli Lily Pharmaceuticals, Indianapolis, USA, July 29th, 2010. 55. Parkinsons Disease Therapeutics Conference organized by the Michael J Fox Foundation and the New York Academy of Sciences, New York, USA. October 6th, 2010. 56. Keynote speaker: Selected by the students to give the keynote lecture at the 1st Instituto de Tecnologia Química e Biológica (ITQB) PhD Students Conference, The New University of Lisbon, October 21-22nd, 2010, Portugal. 57. One of 5 panelist at the Future of Education Summit, session (Closing the GAP), World Economic Forum on the Middle East and North Africa, Marrakech, Morocco, Oct 25-28, 2010 58. ?-Synuclein in health and disease 2010, San Diego, USA, November 11-12th, 2010 2009 59. Boehringer Ingelheim Pharma GmbH & Co. KG, January 21-22, 2009 60. Structure of Amyloid Fibrils and Mechanism of their Formation, Halle (Saale), Germany, 8-11 February 2009. 61. Workshop of the International Graduate College Molecular Complexes of Biomedical Relevance Braunschweig, Germany, 2526 April 2009 62. Conférences Jacques Monod: Protein folds in infectious and neurodegenerative diseases Aussois (Savoie), France, 25-29 April 2009. 63. World Economic Forum on the Middle East, Dead Sea, Jordan, May 15-17, 2009 64. University of Leuven, Faculty of Sciences, Department of Chemistry, Leuven, Belgium, May 27th, 2009 65. 4th European Society of Neurochemistry Conference on Advances in Molecular Mechanisms of Neurological Diseaeses, Mechanisms in synucleinopathies Leipzig, Germany, July 11-14th, 2009. 66. Genentech, San Francisco, CA, June 24th, 2009 67. Eli Lilly, Indiana, June 26th, 2009. 68. FASEB Summer Research Conference on Amyloid Fibril Formation and Protein Misfolding: Molecular Mechanisms and Cellular Effects, Snowmass Village, Colorado, USA. June 28 - July 3, 2009. 69. International Conference of Alzheimer's Disease (ICAD), Featured symposium on "Pathophysiological role of alpha-synuclein in Parkinson's disease and dementia".Vienna, Austria, July 14th, 2009 70. The International Society for Neurochemistry, Synucleinopathies mechanisms, models and therapeutic strategies, Bejing, Aug 29-30, 2009. 71. Japanese-Switzerland Biomolecular Chemistry Symposium, Tokyo, Japan. Sept 11-12th. 72. Seoul National University, Department of Pharmacology, Seoul, South Korea, Sept 14th, 2009. 73. KonkuK University, Department of Biomedical Sciences, Institute of Biomedical Sciences and Technology, Seoul, South Korea, Sept 16, 2009. 74. Institut de Recherche en Ophtalmologie (IRO), Sion, Switzerland, Sept 22, 2009. 75. Summar School on Dopaminergic Neurons, Trieste, Italy, October 5-6, 2009. 76. 3rd International MIF Symposium, Schloß Hochhausen, Germany, December 3-5, 2009 2008 77. Grand Challenge Speaker, Institute of Complex Adaptive Matter Annual Conference, Santa Fe, New Mexico, January 14-17th, 2008 78. Elan Pharamceuticals, San Francisco, January 13th, 2008 79. 1st International Conference on Drug Design and Discovery, Dubai, UAE, Feb 3-6, 2008. 80. Fassberg lecturer, Max Plank Institute for Biophysical Chemistry, Göttingen, Germany, February 19th, 200 81. Institute De Biologie Structurale et Microbiologie CNRS / IBSM, Marseille, France, March 5th, 2008 82. Annual Meeting of the German Society for Cell Biology, A symposium on Pathologic aggregation of proteins. Marburg, Germany, March 12-15, 2008 83. Shanghai Medical College of Fudan University, Shanghai, China, March 28th, 2008 Future Medicine, Faculty of Medicine, Alexandria University, Egypt, May 14-16, 2008. 84. World Economic Forum (WEF), WEF, Face-to-Face meeting with Global Leadership Fellows, Cologny, Geneva, Switzerland, June 10th, 2008. 85. 6th FENS (Federation of European Neuroscience Societies) Conference: Symposium on Molecular mechanisms in Parkinson¹s disease and other synucleinopathies. 6th FENS, Geneva, Switzerland, July 12-16, 2008 86. ?-Synuclein in Health and Disease, Lausanne, Switzerland, September 24-26th, 2008. 87. International Symposium on Medicinal Chemistry (EFMC-ISMC 2008), Vienna, Austria, August 31 September 4, 2008 88. Organic Chemistry and Biochemistry Colloquium, Department of Biochemistry, Technical University of Munich, Germany, October 30th, 2008. 89. Michael J. Fox Foundation for Parkinsons Research, New York, USA, November 8th, 2008. 90. Merck/Serono, Geneva, Nov 27th, 2008. 91. Institut de Recerca Biomèdica Parc Científic de Barcelona, Barcelona, Spain, December 5th, 2008. 92. New York Academy of Sciences Symposium "Tau and Beyond: Phosphorylation in Neurodegenerative Disorders", New York, USA, December 9th, 2008. 93. United Arab Emirates University, Faculty of Medicine Neuroscience Seminar Series, December 23rd, 2008. 2007 94. Keynote Speaker, Lake Geneva Innovation Society (LGIS) Gala Dinner, Geneva, Switzerland, January 23rd. 95. Verbier Neural Workshop. Nutrition, Exercise and Neurodegenerative Diseases, January 28-31st, 2007. 96. The Ringber Meeting 2007. Molecular basis of toxic protein conformation, Ringberg Castle, Bavaria, Germany, February 18-21st, 2007. 97. Wyeth Research, Neuroscience Discovery Research, Princeton, New Jersey, USA, March 1-2. 98. Banbury Center, Cold Spring Harbor "When is Amyloid Functional and When is Amyloidogenesis Pathological? New York, USA, March 11-14th. 99. Third meeting on the "Molecular Mechanisms of Neurodegeneration, Milan, Italy, May 19-21, 2007. Technical University of Braunschweig, Institute of Biochemistry and Biotechnology, May 23, 2007 100. Keynote Speaker, EndoNeuro meeting: The annual Dutch meeting for molecular and cellular neuroscience. Molecular aspects of alpha-synuclein aggregation in Neurodegeneration, Doorwerth, The Netherland, June 5-8th, 2007 101. University of Twente, Enschede, The Netherlands, June 8, 2007. 102. Plenary speaker, Frontiers in Chemical Biology Symposium, University of Strathclyde, Scotland, UK, June 16, 2007. 103. Plenary Speaker, New Frontiers in Basic and Clinical Research in Parkinson's disease and other synucleinopathies Queensland, Australia, July 5-6, 2007. 104. Protein Assembly in Materials, Biology, and Medicine, Direct impact on biological nanosciences, Crete, Greece, Capsis Hotel, July 7-10. 105. FENS Summer School, Molecular Strategies for treating neurodegenerative diseases, Ofir, Portugal, July 8-15, 2007. 106. Alpine Meeting Molecular basis of disease, Valens Switzerland, August 16-19th 107. 9th International Conference on Transglutaminases and protein cross linking, Marrakech, Morocco, Sept 1-5, 2007. 108. Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Göttingen, Germany, Oct 23rd 2007. 109. INSERM U679 (former U289) Thérapeutique et Neurologie Expérimentale Hôpital de la Pitié-Salpêtrière, Nov 9th 2007 110. Biophysics Colloquia, Department of Chemistry, Cambridge University, Cambridge, UK, Nov 30th, 2007. 111. Qfirst2007 Doha Conference, Towards Partnership in Research with Arab Expatriate Scientists to Achieve Sustainable Development in Qatar, Doha, December 10-12th, 2007. 2006 112. Novartis Pharmaceuticals, Basel, Switzerland. January 10th, 2006. 113. Biozentrum, University of Basel, January 24th, 2006. 114. Workshop on amyloid formation. The structure of amyloid aggregates, the mechanism of their formation and the molecular basis of cell dysfunction Firenze, Italy March 25-28, 2006. 115. The annual meeting of the German Society of Human Genetics, "Molecular mechanisms in Huntington disease protein misfolding", Heidelberg, Germany, March 8, 2006. 116. School of Sciences, Taiz University, Republic of Yemen, April 20th, 2006 117. International Conference From Sold State to Biophysics III Dubrovnik, Croatia, June 24-July 1st, 2006. 118. Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Göttingen, Germany, May 21, 2006. 119. Symposium on Protein Transport, Synaptic Function and Neurodegenerative Diseases. European Neuroscience Institute, Göttingen, Germany, Sep 3, 2006. 120. The European BioAlpine Convention, Grenoble- Keynote Speaker, France, October 6, 2006. 121. Department of Theoretical Biology, Peking University, Beijing, China, November 19-21st, 2006. 122. Visiting Professor, Universiti Teknologi Malaysia, Skudai, Johor, Malaysia, November 21-24, 2006. 2005 123. Ph.D. Course in Protein Fibrillation and Aggregation. Aalborg University, Denmark, May 17-20. 124. The Second Japan-Switzerland Workshop on Biomechanics "New Trends in Biomechanics: from Biomolecule to Tissue. Kyoto, Japan. September 12 -16, 2005. 125. University of Geneva, Department of Biochemistry and Structural Biology Seminar, Geneva, June 17th. 126. The 3rd Lemanic Neuroscience Conference, Diablerets, Switzerland. 127. Nathan Shock Center Conference on Aging: The Role of Protein Misfolding and Aggregation on Aging and Age-Related Disorders. San Antonio, Texas, October 27-30, 2005. 128. International Neuroscience conference in the United Arab Emirates, November 26-29, 2005. 129. FENS/HERTIE winter school. Neurodegenerative Aggregation Disorders: from genes to protein aggregation, neuronal dysfunction and experimental treatments. Kitzbuhel, Austria, December 2005. 130. The Second Japan-Switzerland Workshop on Biomechanics "New trends in Biomechanics: from biomolecule to tissue. Kyoto, Japan. September 12 16 2004 131. 10th Neural Workshop Verbier, Molecular, Cellular and Clinical Aspects of Neurodegenerative Diseases Verbier, Switzerland, January, 2004. 132. Institute for Complex Adaptive Matter Workshop. Protein Misaggregation: from Biomolecules to Neurodegeneration. Boston, MA, February 9th- 11, 2004. 133. Washington University School of Medicine, St. Louis, Alzheimers disease research center seminar, April 20th, 2004. 134. Clark University, Department of Chemistry and Biochemistry. Worcester, MA, April 28th, 2004. 135. King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, April 30th May 5th. 136. Dutch Endo Neuro Psycho meeting of 2004. Annual meeting for scientists of fundamental and clinical endocrinology, neuroendocrinology and neuroscience. Amsterdam, Netherlands June 1-3, 2004 137. Netherlands Brain Institute, Amsterdam, Netherlands, June 4th, 2004. 138. Institute de Recerca Biomèdica de Barcelona, Barcelona, Spain, June 10-11th, 2004. 139. The Siwss Federal Institute of Technology (EPFL), Lausanne, Switzerland, June 7th-9th. 140. Summer Neuropeptide 2004 Conference, Miami, July 5-9, 2004. 141. Washington University School of Medicine, St. Louis, Department of Biochemistry seminar, July 23th, 2004. 142. FEBS research course "New molecular strategies to treat neurodegenerative diseases". Ofir Portugal, July 17-23, 2004. 143. University of Texas Health Science Center, San Antonio, Texas. Department of Biochemistry, July 25th, 2004. 2003 144. Boehringer Ingelheim Fonds Internalional Titisee Conferences Alzheimers and Parkinsons Disease: From Basic Science to Therapeutic Treatment. Germany, Titise/Black Forest, March 19-23, 2003. 145. Third Multidisciplinary Workshop: Self-assembling Peptides & Protein Systems in Biology, Medicine and Engineering Crete, Greece, August, 2003. 146. Lady Davis Institute for Medical Research, Montreal, Canada, August 27th, 2003. 147. Rensselaer Polytechnic Institute, Department of Chemistry Seminar Series. Protein fibrillogenesis in Neurodegenerative Diseases: From Biophysics to Therapeutic Strategies. Albany, NY September 2nd, 2003. 148. University of Rhode Island's Department of Biomedical Sciences, Rhode Island, November 2003. 2002 149. University of California San Francisco, Physical Properties of Amyloid Diseases, San Francisco, CA. December, 25-27 2002 150. Parkinsons Institute, Protein Fibrillogenesis in Parkinsons Disease, Sunnyvale, CA.December, 28 2002 151. Massachusetts Institute of Technology, Department of Biology: Structural Biology Seminar, March, 18, 2002. 152. American Chemical Society National Meeting, Structural and Mechanistic Aspects of Amyloid Fibril Formation Orlando Florida, April, 7-11 2002. 153. FASEB Meeting: Amyloid and Other Abnormal Protein Processes, Colorado, June, 15-20 2002. 154. Biogen,Inc, Cambridge, MA, September, 6th, 2002. 155. Protein Folding and Disease: The Horizon Symposia Protein Folding and Disease organized by Nature Publishing Group and Aventis. Verona, Italy, October, 2-5th 2002. 156. Elan BioPharmaceuticals, San Francisco, CA, October 13, 2002. 157. RIKEN Brain Science Institute: The first international workshop of molecular neuropathology Frontiers in Molecular Neuropathology Japan, November, 27-29 2002. 2001 158. King Fahed University of Petroleum and Minerals, Department of Chemistry Seminar, Dhahran, Saudi Arabia, April, 2001.Other Activities
Dr. Lashuel is also one of the co-founders and secretary general of the society for advancing science and technology in the Arab World (SASTA), (http://sastaworld.com) that was founded in 2010. SASTAs mission is to contribute to the advancement of science, technology, higher education and research in the Arab region through supporting scientific human capacity building, development of academic and research programs and providing scientific, technical and material support to local academic, scientists and universities. His contribution to promoting higher education and research in the Middle East is also exemplified by 1) his role as a co-founder and co-director of the American Association of Yemeni Scientists and Professionals (www.aaysp.org), an organization focused on promoting higher education and research in Yemen and among the Yemeni communities in the United States; 2) his active involvement as a member of the Arab Expatriate Scientists Follow up Committee appointed by Her Highness Sheikha Mozah bint Nasser Al-Missned (http://www.qf-qfirst.info/ ) and coordinator of the biomedical group of Arab Expatriate Scientists. Dr. Lashuel also serves as a research advisor to universities in the region and continues to work actively to engage international organizations, including the World Economic Forum (WEF) and the International Brain Research Organization (IBRO), to promote higher education and research in the Middle East and North Africa (MENA). Dr. Lashuel is one of the founding members of the IBRO-MENA subregion chapter, which is an IBRO affiliated and funded organizations that aims to promote neuroscience research in the MENA region. In collaboration with the World Economic Forum, Dr. Lashuel and the leadership of SASTA are working with other Arab scientists to engage with business leaders and policy makers from the region and formulate specific recommendations focused on promoting Education, Science and Technology as catalysts for transformation and development in the region. He has been invited to participate as a speaker or panelist in the regional WEF summits at the Dead Sea (2009, 2011 and 2013), Marrakech (2010), the Global Redesign Summit in Doha (2010), and WEF Annual Meeting in Davos (2012).Education
PhD
Chemistry/Biophysics
Texas A&M University and The Scripps Research Institute
1994-2000
B. Sc
Chemistry
City University of New York, Brooklyn College
1990-1994
Publications
Infoscience publications
Infoscience
Post-translational glycosylation diminishes α-synuclein pathology formation
Nature Chemical Biology. 2024-02-14. DOI : 10.1038/s41589-024-01553-0.O-GlcNAc forces an α-synuclein amyloid strain with notably diminished seeding and pathology
Nature Chemical Biology. 2024-02-12. DOI : 10.1038/s41589-024-01551-2.Author Correction: Fully co-factor-free ClearTau platform produces seeding-competent Tau fibrils for reconstructing pathological Tau aggregates
Nature Communications. 2024. DOI : 10.1038/s41467-024-48976-w.Drug Screening in C. elegans to identify new pharmacological mitochondrial stress inducers
Lausanne, EPFL, 2024. DOI : 10.5075/epfl-thesis-10537.Method of preparation of amyloidogenic protein aggregates and uses thereof
WO2024094597 . 2024.Effective Inhibition of TDP-43 Aggregation by Native State Stabilization
Angewandte Chemie-International Edition. 2024. DOI : 10.1002/anie.202314587.Targeting TDP-43 Proteinopathies in Neurodegeneration by its Native-State Stabilization
Lausanne, EPFL, 2024. DOI : 10.5075/epfl-thesis-10555.Recombinant Full-Length TDP-43 Oligomers Retain Their Ability to Bind RNAs, Are Not Toxic, and Do Not Seed TDP-43 Aggregation in Vitro
Acs Chemical Neuroscience. 2023-12-20. DOI : 10.1021/acschemneuro.3c00691.Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases
Npj Parkinsons Disease. 2023-12-07. DOI : 10.1038/s41531-023-00604-y.Why computational complexity may set impenetrable barriers for epistemic reductionism
Synthese. 2023-10-24. DOI : 10.1007/s11229-023-04366-1.Fully co-factor-free ClearTau platform produces seeding-competent Tau fibrils for reconstructing pathological Tau aggregates
Nature Communications. 2023-07-04. DOI : 10.1038/s41467-023-39314-7.Overexpression of human alpha-Synuclein leads to dysregulated microbiome/metabolites with ageing in a rat model of Parkinson disease
Molecular Neurodegeneration. 2023-07-04. DOI : 10.1186/s13024-023-00628-1.Neuronal growth on high-aspect-ratio diamond nanopillar arrays for biosensing applications
Scientific Reports. 2023-04-11. DOI : 10.1038/s41598-023-32235-x.Exploring the interplay of molecular pattern and valency for selective interactions at the bio-interface
Lausanne, EPFL, 2023. DOI : 10.5075/epfl-thesis-10292.Engineering Innate and Adaptive Immunity for Enhanced Cancer Immunotherapy
Lausanne, EPFL, 2023. DOI : 10.5075/epfl-thesis-10086.Deconstructing and Reconstructing the Complexity of Tau pathology
Lausanne, EPFL, 2023. DOI : 10.5075/epfl-thesis-9911.Prominent astrocytic alpha-synuclein pathology with unique post-translational modification signatures unveiled across Lewy body disorders
Acta Neuropathologica Communications. 2022-11-12. DOI : 10.1186/s40478-022-01468-8.Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity
Npj Parkinsons Disease. 2022-10-20. DOI : 10.1038/s41531-022-00388-7.N-terminal mutant huntingtin deposition correlates with CAG repeat length and symptom onset, but not neuronal loss in Huntington's disease
Neurobiology Of Disease. 2022-10-11. DOI : 10.1016/j.nbd.2022.105884.Pathological substrate of memory impairment in multiple system atrophy
Neuropathology And Applied Neurobiology. 2022-08-12. DOI : 10.1111/nan.12844.Identification of key segments of IAPP/aSyn cross-amyloid interactions
2022-08-01.Opportunities and challenges of alpha-synuclein as a potential biomarker for Parkinson's disease and other synucleinopathies
Npj Parkinsons Disease. 2022-07-22. DOI : 10.1038/s41531-022-00357-0.Remembering John Q Trojanowski, in his own words: A life dedicated to discovering building blocks and using them to build bridges of knowledge, collaboration, and discovery
Npj Parkinsons Disease. 2022-04-12. DOI : 10.1038/s41531-022-00310-1.A NAC domain mutation (E83Q) unlocks the pathogenicity of human alpha-synuclein and recapitulates its pathological diversity
Science Advances. 2022-04-01. DOI : 10.1126/sciadv.abn0044.Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson's Disease and Multiple System Atrophy
Cells. 2022-03-01. DOI : 10.3390/cells11050906.Towards elucidating the structural and cellular determinants of a-synuclein seeding and toxicity
Lausanne, EPFL, 2022. DOI : 10.5075/epfl-thesis-9365.Comparative Analysis of Total Alpha-Synuclein (alpha SYN) Immunoassays Reveals That They Do Not Capture the Diversity of Modified alpha SYN Proteoforms
Journal Of Parkinsons Disease. 2022-01-01. DOI : 10.3233/JPD-223285.Capturing the heterogeneity of alpha-synuclein pathology in synucleinopathies
Lausanne, EPFL, 2022. DOI : 10.5075/epfl-thesis-8480.Alpha-synuclein as a Potential Biomarker for Parkinson’s Disease and Other Synucleinopathies: Gaps, Challenges, and Opportunities
2022-03-12.Multidisciplinary Investigation of the Gut-Brain Ecosystem in a Model of Alzheimer's Disease
Lausanne, EPFL, 2022. DOI : 10.5075/epfl-thesis-8532.An integrative approach to elucidate the mechanisms and dynamics of Huntingtin aggregation and inclusion formation in neuronal models of Huntington's Disease
Lausanne, EPFL, 2022. DOI : 10.5075/epfl-thesis-9296.Non-monotonic fibril surface occlusion by GFP tags from coarse-grained molecular simulations
Computational and Structural Biotechnology Journal. 2022. DOI : 10.1016/j.csbj.2021.12.017.Revisiting the grammar of Tau aggregation and pathology formation: how new insights from brain pathology are shaping how we study and target Tauopathies
Chemical Society Reviews. 2022. DOI : 10.1039/d1cs00127b.To target Tau pathologies, we must embrace and reconstruct their complexities
Neurobiology Of Disease. 2021-12-01. DOI : 10.1016/j.nbd.2021.105536.Nuclear and cytoplasmic huntingtin inclusions exhibit distinct biochemical composition, interactome and ultrastructural properties
Nature Communications. 2021-11-12. DOI : 10.1038/s41467-021-26684-z.Fatal attraction-The role of hypoxia when alpha-synuclein gets intimate with mitochondria
Neurobiology Of Aging. 2021-11-01. DOI : 10.1016/j.neurobiolaging.2021.07.017.The Nt17 Domain and its Helical Conformation Regulate the Aggregation, Cellular Properties and Neurotoxicity of Mutant Huntingtin Exon 1
Journal of Molecular Biology. 2021-10-15. DOI : 10.1016/j.jmb.2021.167222.Pharmacological characterization of mutant huntingtin aggregate-directed PET imaging tracer candidates
Scientific Reports. 2021-09-09. DOI : 10.1038/s41598-021-97334-z.Alpha-synuclein research: defining strategic moves in the battle against Parkinson's disease
Npj Parkinsons Disease. 2021-07-26. DOI : 10.1038/s41531-021-00203-9.Investigating Crosstalk Among PTMs Provides Novel Insight Into the Structural Basis Underlying the Differential Effects of Nt17 PTMs on Mutant Httex1 Aggregation
Frontiers in Molecular Biosciences. 2021-07-26. DOI : 10.3389/fmolb.2021.686086.A New Chemoenzymatic Semisynthetic Approach Provides Insight into the Role of Phosphorylation beyond Exon1 of Huntingtin and Reveals N-Terminal Fragment Length-Dependent Distinct Mechanisms of Aggregation
Journal of the American Chemical Society. 2021-06-23. DOI : 10.1021/jacs.1c03108.Rethinking protein aggregation and drug discovery in neurodegenerative diseases: Why we need to embrace complexity?
Current Opinion in Chemical Biology. 2021-06-23. DOI : 10.1016/j.cbpa.2021.05.006.Lewy body-associated proteins: Victims, instigators, or innocent bystanders? The case of AIMP2 and alpha-synuclein
Neurobiology of Disease. 2021-06-06. DOI : 10.1016/j.nbd.2021.105417.Parkinson mice show functional and molecular changes in the gut long before motoric disease onset
Molecular Neurodegeneration. 2021-06-02. DOI : 10.1186/s13024-021-00439-2.Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the UPR in models of neurodegeneration
Molecular Therapy. 2021-05-05. DOI : 10.1016/j.ymthe.2021.01.033.Correlative light and electron microscopy suggests that mutant huntingtin dysregulates the endolysosomal pathway in presymptomatic Huntington's disease
Acta Neuropathologica Communications. 2021-04-14. DOI : 10.1186/s40478-021-01172-z.Alpha-Synuclein oligomerization and aggregation: All models are useful but only if we know what they model This is the reply to a comment "Alpha-synuclein oligomerization and aggregation: A model will always be a model" on the original article "Monitoring alpha-synuclein oligomerization and aggregation using bimolecular fluorescence complementation assays: What you see is not always what you get". The articles are accompanied by a Preface "How good are cellular models?".
Journal Of Neurochemistry. 2021-03-22. DOI : 10.1111/jnc.15275.Hypoxia Conditioning as a Promising Therapeutic Target in Parkinson's Disease?
Movement Disorders. 2021-02-27. DOI : 10.1002/mds.28544.Reverse engineering Lewy bodies: how far have we come and how far can we go?
Nature Reviews Neuroscience. 2021-01-11. DOI : 10.1038/s41583-020-00416-6.Enhancing mitochondrial quality control to fight neuromuscular degeneration in aging and disease
Lausanne, EPFL, 2021. DOI : 10.5075/epfl-thesis-8834.Monitoring alpha-synuclein oligomerization and aggregation using bimolecular fluorescence complementation assays: What you see is not always what you get
Journal of Neurochemistry. 2021. DOI : 10.1111/jnc.15147.Site-Specific Phosphorylation of Huntingtin Exon 1 Recombinant Proteins Enabled by the Discovery of Novel Kinases
Chembiochem. 2020-10-13. DOI : 10.1002/cbic.202000508.How specific are the conformation-specific α-synuclein antibodies? Characterization and validation of 16 α-synuclein conformation-specific antibodies using well-characterized preparations of α-synuclein monomers, fibrils and oligomers with distinct structures and morphology
Neurobiology of Disease. 2020-09-22. DOI : 10.1016/j.nbd.2020.105086.TBK1 phosphorylates mutant Huntingtin and suppresses its aggregation and toxicity in Huntington's disease models
The EMBO Journal. 2020-08-05. DOI : 10.15252/embj.2020104671.Half a century of amyloids: past, present and future
Chemical Society Reviews. 2020-07-07. DOI : 10.1039/C9CS00199A.Do Lewy bodies contain alpha-synuclein fibrils? and Does it matter? A brief history and critical analysis of recent reports
Neurobiology Of Disease. 2020-07-01. DOI : 10.1016/j.nbd.2020.104876.Phosphorylation of the overlooked tyrosine 310 regulates the structure, aggregation, and microtubule- and lipid-binding properties of Tau
Journal Of Biological Chemistry. 2020-06-05. DOI : 10.1074/jbc.RA119.012517.Extent of N-terminus exposure of monomeric alpha-synuclein determines its aggregation propensity
Nature Communications. 2020-06-04. DOI : 10.1038/s41467-020-16564-3.Education and research are essential for lasting peace in Yemen
Lancet. 2020-04-04. DOI : 10.1016/S0140-6736(20)30162-8.Unraveling the complexity of amyloid polymorphism using gold nanoparticles and cryo-EM
Proceedings Of The National Academy Of Sciences Of The United States Of America. 2020-03-24. DOI : 10.1073/pnas.1916176117.The busy lives of academics have hidden costs — and universities must take better care of their faculty members
Nature Careers Community. 2020-03-05. DOI : 10.1038/d41586-020-00661-w.A simple, versatile and robust centrifugation-based filtration protocol for the isolation and quantification of alpha-synuclein monomers, oligomers and fibrils: Towards improving experimental reproducibility in alpha-synuclein research
Journal Of Neurochemistry. 2020-02-25. DOI : 10.1111/jnc.14955.The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration
Proceedings of the National Academy of Sciences of United States of America. 2020-02-19. DOI : 10.1073/pnas.1913904117.Site-Specific Hyperphosphorylation Inhibits, Rather than Promotes, Tau Fibrillization, Seeding Capacity, and Its Microtubule Binding
Angewandte Chemie-International Edition. 2020-01-28. DOI : 10.1002/anie.201913001.Ultrasensitive quantitative measurement of huntingtin phosphorylation at residue S13
Biochemical And Biophysical Research Communications. 2020-01-15. DOI : 10.1016/j.bbrc.2019.09.097.What about faculty?
Elife. 2020-01-08. DOI : 10.7554/eLife.54551.Development of novel methods and tools to decipher the huntingtin post-translation modifications code
Lausanne, EPFL, 2020. DOI : 10.5075/epfl-thesis-7537.Pronounced α-synuclein pathology in a seeding-based mouse model is not sufficient to induce mitochondrial respiration deficits in the striatum and amygdala
eNeuro. 2020. DOI : 10.1523/ENEURO.0110-20.2020.Gold nanoparticles as a new tool in amyloid studies
Lausanne, EPFL, 2020. DOI : 10.5075/epfl-thesis-7471.The Role of Post-translational Modifications on the Energy Landscape of Huntingtin N-Terminus
Frontiers in Molecular Biosciences. 2019-10-01. DOI : 10.3389/fmolb.2019.00095.Phospho-S129 Alpha-Synuclein Is Present in Human Plasma but Not in Cerebrospinal Fluid as Determined by an Ultrasensitive Immunoassay
Frontiers in Neuroscience. 2019-08-22. DOI : 10.3389/fnins.2019.00889.Investigation of alpha-synuclein post-translational modifications in idiopathic Parkinson's disease and multiple system atrophy
2019-03-01. 120th Meeting of the British-Neuropathological-Society (BNS) / Developmental Neuropathology Symposium, London, ENGLAND, Mar 06-08, 2019. p. 19-19.Single Posttranslational Modifications in the Central Repeat Domains of Tau4 Impact its Aggregation and Tubulin Binding
Angewandte Chemie-International Edition. 2019-02-04. DOI : 10.1002/anie.201805238.alpha-Synuclein O-GlcNAcylation alters aggregation and toxicity, revealing certain residues as potential inhibitors of Parkinson's disease
Proceedings Of The National Academy Of Sciences Of The United States Of America. 2019-01-29. DOI : 10.1073/pnas.1808845116.A method for preparing phfs-like tau aggregates
US11629175 ; US2021238242 ; EP3784687 ; WO2019207164 . 2019.Chronic corticosterone aggravates behavioral and neuronal symptomatology in a mouse model of alpha-synuclein pathology
Neurobiol Aging. 2019. DOI : 10.1016/j.neurobiolaging.2019.08.007.Application of anti-amyloid beta immunization using encapsulated cell technology in mouse models of Alzheimer's disease
Lausanne, EPFL, 2019. DOI : 10.5075/epfl-thesis-9751.Development of Tissue Kallikrein Inhibitors for the Treatment of Netherton Syndrome
Lausanne, EPFL, 2019. DOI : 10.5075/epfl-thesis-7676.A viral vector based in vivo model of tauopathy to explore therapeutic strategies against tau pathology
Lausanne, EPFL, 2019. DOI : 10.5075/epfl-thesis-9532.Axon regeneration and circuit reorganization after complete spinal cord injury
Lausanne, EPFL, 2019. DOI : 10.5075/epfl-thesis-7659.Antibody-based methods for the measurement of α-synuclein concentration in human cerebrospinal fluid - method comparison and round robin study
Journal of Neurochemistry. 2019. DOI : 10.1111/jnc.14569.Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy
Journal of Visualized Experiments. 2018-03-29. DOI : 10.3791/57506.Exploring the role of post-translational modifications in regulating α-synuclein interactions by studying the effects of phosphorylation on nanobody binding
Proteins Science. 2018-03-29. DOI : 10.1002/pro.3412.N-terminal Huntingtin (Htt) phosphorylation is a molecular switch regulating Htt aggregation, helical conformation, internalization, and nuclear targeting
Journal of Biological Chemistry. 2018-09-05. DOI : 10.1074/jbc.RA118.004621.Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid α-synuclein fibrils
Proceedings of the National Academy of Sciences. 2018-06-25. DOI : 10.1073/pnas.1721220115.Resolving molecule-specific information in dynamic lipid membrane processes with multi-resonant infrared metasurfaces
Nature Communications. 2018-06-04. DOI : 10.1038/s41467-018-04594-x.Real-time in-situ secondary structure analysis of protein monolayer with mid-infrared plasmonic nanoantennas
ACS Sensors. 2018-05-30. DOI : 10.1021/acssensors.8b00115.Protein Semisynthesis Provides Access to Tau Disease-Associated Post-translational Modifications (PTMs) and Paves the Way to Deciphering the Tau PTM Code in Health and Diseased States
Journal of the American Chemical Society. 2018-04-24. DOI : 10.1021/jacs.8b02668.Combined Multi-Plane Tomographic Phase Retrieval and Stochastic Optical Fluctuation Imaging for 4D Cell Microscopy
Nature Photonics. 2018. DOI : 10.1038/s41566-018-0109-4.Ganciclovir derivatives for modulating innate and adaptive immunity and for use in immunotherapy
US9809597 ; US2017050967 . 2017.Activation of the STING-dependent type I interferon response reduces microglial reactivity and neuroinflammation
Neuron. 2017. DOI : 10.1016/j.neuron.2017.11.032.Phosphorylation of huntingtin at residue T3 is decreased in Huntington’s disease and modulates mutant huntingtin protein conformation
Proceedings of the National Academy of Sciences. 2017. DOI : 10.1073/pnas.1705372114.Monomeric Huntingtin Exon 1 Has Similar Overall Structural Features for Wild-Type and Pathological Polyglutamine Lengths
Journal of the American Chemical Society. 2017. DOI : 10.1021/jacs.7b06659.Membrane scission driven by the PROPPIN Atg18
Embo Journal. 2017. DOI : 10.15252/embj.201796859.Sequence and structural determinants of Tau aggregation and seeding capacity: Implications for Neurofibrillary Tangle formation and Tau toxicity in Alzheimer's disease
Lausanne, EPFL, 2017. DOI : 10.5075/epfl-thesis-7985.Amyloid Single Cell Cytotoxicity Assays by Nanomotion Detection
Cell Death Discovery. 2017. DOI : 10.1038/cddiscovery.2017.53.Discovery and characterization of novel stable tau oligomeric complexes: Implications for the role of Tau/phospholipid interactions in regulating its functions in health and disease
Nature Communications. 2017. DOI : 10.1038/s41467-017-01575-4.A user's guide for α-synuclein biomarker studies in biological fluids: Perianalytical considerations
Movement Disorders. 2017. DOI : 10.1002/mds.27090.Polyglutamine expansion affects huntingtin conformation in multiple Huntington’s disease models
Scientific Reports. 2017. DOI : 10.1038/s41598-017-05336-7.Polyglutamine Length Dependent Structural Properties and Phase Behavior of Huntingtin Exon 1
2017. 58th Annual Meeting of the Biophysical-Society, San Francisco, CA, FEB 15-19, 2014. p. 511A-511A. DOI : 10.1016/j.bpj.2016.11.2762.Post-translational glycosylation diminishes α-synuclein pathology formation
Nature Chemical Biology. 2024-02-14. DOI : 10.1038/s41589-024-01553-0.O-GlcNAc forces an α-synuclein amyloid strain with notably diminished seeding and pathology
Nature Chemical Biology. 2024-02-12. DOI : 10.1038/s41589-024-01551-2.Author Correction: Fully co-factor-free ClearTau platform produces seeding-competent Tau fibrils for reconstructing pathological Tau aggregates
Nature Communications. 2024. DOI : 10.1038/s41467-024-48976-w.Drug Screening in C. elegans to identify new pharmacological mitochondrial stress inducers
Lausanne, EPFL, 2024. DOI : 10.5075/epfl-thesis-10537.Method of preparation of amyloidogenic protein aggregates and uses thereof
WO2024094597 . 2024.Effective Inhibition of TDP-43 Aggregation by Native State Stabilization
Angewandte Chemie-International Edition. 2024. DOI : 10.1002/anie.202314587.Targeting TDP-43 Proteinopathies in Neurodegeneration by its Native-State Stabilization
Lausanne, EPFL, 2024. DOI : 10.5075/epfl-thesis-10555.Recombinant Full-Length TDP-43 Oligomers Retain Their Ability to Bind RNAs, Are Not Toxic, and Do Not Seed TDP-43 Aggregation in Vitro
Acs Chemical Neuroscience. 2023-12-20. DOI : 10.1021/acschemneuro.3c00691.Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases
Npj Parkinsons Disease. 2023-12-07. DOI : 10.1038/s41531-023-00604-y.Why computational complexity may set impenetrable barriers for epistemic reductionism
Synthese. 2023-10-24. DOI : 10.1007/s11229-023-04366-1.Fully co-factor-free ClearTau platform produces seeding-competent Tau fibrils for reconstructing pathological Tau aggregates
Nature Communications. 2023-07-04. DOI : 10.1038/s41467-023-39314-7.Overexpression of human alpha-Synuclein leads to dysregulated microbiome/metabolites with ageing in a rat model of Parkinson disease
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Mission and Research Interest
Our Mission: To elucidate the molecular mechanisms underlying neurodegeneration in Alzheimer's and Parkinson's disease and develop novel strategies to facilitate the diagnosis, prevention and treatment of these diseases. Our Research Goals 1. Elucidation of the relationship between the processes of protein misfolding and aggregation and neurodegeneration in Alzheimers disease (AD), Parkinsons disease (PD) and related neurodegenerative disorders. 2. To understand the molecular mechanisms through which disease-associated variants and post-translational modification of the gene products associated with AD and PD induce neuronal dysfunction and neurodegeneration. 3. Develop novel therapeutic strategies based on modulating protein aggregation and clearance. Research interest: Current research in the Lashuel laboratory focuses on applying chemical, biophysical, structural and molecular biology approaches to understanding the molecular and structural basis of protein misfolding and self-assembly and the mechanisms by which these processes contribute to the physiological and pathogenic properties of specific proteins implicated in neurodegenerative diseases. Current research efforts cover the following topics: (1) Elucidating the molecular and cellular determinants underlying amyloid-? and ?-synuclein aggregation and toxicity in Alzheimers diseases and Parkinsons disease and related disorders. (2) Elucidating the structural basis of amyloid-associated toxicity by correlating the structural properties of defined aggregates in the amyloid pathway to their toxicity in primary neuronal cultures; (3) Developing innovative chemical approaches and novel tools to monitor and control protein folding/misfolding and self-assembly in vitro and in vivo with spatial and temporal resolution; (4) Understanding the role of post-translational modifications in the pathogenesis of neurodegenerative diseases; (5) Identifying and validating new therapeutic targets for treating Parkinsons disease; (6) Developing novel therapeutic strategies to treat neurodegenerative diseases based on modulation of protein aggregation and clearance. Research in the Lashuel lab is funded by several international funding agencies and foundations, including the Swiss National Science Foundation, European FP7 program (Marie Curie and ERC grants), Human Science Frontiers, Strauss Foundation, Cure the Huntingtons disease foundation and Michael J Fox foundation and is supported by collaborations with pharmaceutical and biotech companies (http://lashuel-lab.epfl.ch/page-50538-en.html), Nestle, Merck-Serono, AC Immune and Johnson and Johnson.Teaching & PhD
Teaching
Life Sciences Engineering