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Hilal Lashuel
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Laboratory of Molecular Neurobiology and Neuroproteomics
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Assistant Professor in Neuroscience
birth date: 15.01.1973
nationality: USA
web site: http://nmnf.epfl.ch
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office(s):
AI2151
BCH5209
phone(s): [+41 21 69] 39691,30792,30551
fax: 41 21 693 96 65
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MISSION
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Research Projects in the laboratory of Molecular Neurobiology and Functional Neuroproteomics cover the following topics: (1) Elucidating the structural basis of amyloid-associated toxicity in neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's disease; (2) Understanding the role of quaternary structure in protein function and disease; (3) Exploiting amyloid fibril formation for constructing polypeptide materials with potential applications in biotechnology and medicine.
for more information about our group, visit our website at http://nmnf.epfl.ch
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BIOGRAPHY
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1990-1994 B.S. City University of New York, Brooklyn College
1994-1999 PhD. Texas A&M University, College Station, TX.
The Scripps Research Institute, LaJolla, CA.
2000-2001 Research Scientist: The Picower Institute for Medical Research
Great Nick, NY.
2001 -2002 Postdoctoral Fellow: Harvard Medical School
& the Brigham & Women's Hospital, Boston, MA
2001- 2002 HCNR Fellow: Harvard Center for Neurodegeneration
and Repair (HCNR), Harvard Medical School
2002-2004 Instructor in Neurology: Harvard Medical School
& the Brigham & Women's Hospital, Boston, MA
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 1999. After obtaining his doctoral degree, he became a research fellow at the Picower Institute for Medical Research in Long Island New York where he focused on developing amyloid-based therapeutic strategies for Alzheimer's disease. In 2001, he moved to Harvard Medical School and the Brigham and Women's Hospital as a research fellow in the laboratory of Dr. Peter T. Lansbury at the Center for Neurologic Diseases. In 2001 he received a sabbatical fellowship from Harvard Center for Neurodegeneration and Repair and was later promoted to an instructor in neurology at Harvard Medical School and at the Brigham and Women's Hospital. At Harvard 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.
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Publications
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PUBLICATIONS (Corresponding author *):
1. Mutter M*., Mimna R., Camus M-S., Schmid A., Tuchscherer G., Lashuel HA*. “Switch Peptides: Disruption of amyloid fibrils through controlled induction of -sheet to -helix transformation”. Angewandte Chemie, 2007, In press.
2. Follmer, C, Romao L, Einsiedler C, Porto T, Alves-Lara F, Lashuel HA, Lansbury PT, Neto VM, Silva JL, and Foguel D. “ Dopamine affects the stability, hydration and packing of protofibrils and fibrils of wild-type and variants of a-synuclein”. Biochemistry, 2007, 46, 472-482.
3. Tuchscherer G., Chandravarkar A., Camus MS, Berard J., Schmid A., Bhubaneswar M, Murat K, Mimna R, Lashuel HA., Mutter M. “Switch peptides as folding precursors in self-assembling peptides and amyloid fibrillogenesis”. Biopolymers, 2007, In press.
4. Paleologou KE., Fredenburg RA., Schmid A., Moniatt M., Chiappe D., Lansbury PT and Lashuel HA*. “Dissecting the role of phosphoryaltion in -synuclein aggregation and membrane binding; implications for the pathogenesis of Parkinson’s disease.” Biochemistry. 2007, Submitted
5. Fredenburg RA., Rospigliosi C., Meray R., Kessler JC., Lashuel HA, Eliezer D., and Lansbury PT Jr. “The Impact of the E46K Mutation on the Properties of -Synuclein in its Monomeric and Oligomeric States”. Biochemistry, 2007, submitted
6. Lashuel HA* and Zawia N. “Islam: governments need to reform education and build a scientific culture”. Nature, 2006, 444, 545.
7. Lansbury PT* and Lashuel HA*. “A century-old debate on protein aggregation and neurodegeneration enters the clinic. Nature, 2006, 443, 774-779.
8. Lashuel HA* and Harald Hirling. “Rescuing defective vesicular trafficking protects against -synuclein toxicity in cellular and animal models of Parkinson’s disease. ACS Chemical Biology, 2006, 1(7), 1, 420–424.
9. 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.
10. Saucede L., Santos SD., Chandravarkar A., Mandal B., Murat K., Camus, M-S., Berard, J., Grouzmann, E., Adrian M., Dubochet J., Lopez J., Lashuel HA., Tuchscherer GT., Mutter M. “ “Switch Peptides: From Conformational Studies to Alzaheimer’s Disease”. CHIMIA, 2006, 60, 199-202.
11. Lashuel HA*. "Membrane Permeabilization: A Common Mechanism in Protein Misfolding Diseases: If it look like a pore and acts like a pore, is it a pathogenic pore?". Sci Aging Knowledge Environ. 2005 (38), pe28 (2005). http://sageke.sciencemag.org/content/vol2005/issue38/index.shtml.
12. Wang, L., Lashuel, HA, and Colón, W. From Hexamer to Amyloid: The Mechanism of Serum Amyloid A Fibril Formation. Amyloid: The Journal of Protein Folding Disorders, 2005, 12, 139-148.
13. Lashuel HA*. In Vitro Preparation of Prefibrillar Intermediates of Amyloid- (A) and -Synuclein. Methods Mol Biol. 2005, 299, 19-33.
14. Lashuel HA* and Joseph Wall. Molecular Electron Microscopy Approaches to Elucidating the Mechanism of Amyloid Fibril Formation. Methods Mol Biol. 2005, 299, 81-101.
15. Basha R, Murali M, Siddiqi HK, Ghosal K, Siddiqi OK, Lashuel HA, Zawia NH. Exposure to lead (Pb) promotes b-amyloid aggregation but does not affect the proteolytic processing of the Amyloid Precursor Protein (APP), FASEB J, 2005, 19, 2083-2093.
16. Cox DL, Lashuel HA, Lee KY, and Singh R.R.P. The material science of protein.Aggregation. Material Research Society Bulletin. 2005, 30, 6, 452-459.
17. Morikawa M, Fryer JD, Sullivan PM, Christopher EA, Wahrle SE, DeMattos, O'Dell MA, Fagan AM, Lashuel HA, Walz T, Asai K, and Holtzman D. “Production and characterization of astrocyte-derived human apolipoprotein E isoforms from immortalized astrocytes and their interactions with amyloid-ß “ Neurobiology of Disease, 2005, 19 (1-20), 66-76.
18. Lashuel HA*, Aljabari B, Sigurdsson EM, Metz CN, Leng L, Callaway DJ, and Bucala R. "Amyloid Fibril Formation by Macrophage Migration Inhibitory Factor (MIF)", Biochem. Biophys. Res. Commun, 2005, 6; 338, 973-980.
19. 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):453-67.
20. Rochet JC, Outeiro TF, Conway KA, Ding TT, Volles MJ, Lashuel HA, Bieganski RM, Lindquist SL, and Lansbury PT, Jr. Interactions Among -Synuclein, Dopamine and Biomembranes. J. Mol. Neurosci. 2004, 23, 23-33.
21. 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, 795-805.
22. Ferrao-Gonzales AD, Palmieri L, Valory M, Silva JL, Lashuel HA, Kelly JW, Foguel D. Hydration and Packing are Crucial to Amyloidogenesis as Revealed by Pressure Studies on Transthyretin Variants that Either Protect or Worsen Amyloid Disease. J. Mol. Biol. 2003, 328, 4, 963-974.
23. 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 Parkinson’s Disease and Cancer. 2003, Chemistry & Biology. 2003, 10, 837-846.
24. Kheterpal I*, Lashuel HA*, Hartley DM, Walz T, Lansbury PT Jr., Wetzel R. Aβ protofibrils possess a stable core structure resistant to hydrogen exchange. Biochemistry. 2003, 42, 14092-14098.
25. 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. 2003, 100, 9831-9836.
26. Bitan G, Tarus B, Lashuel HA, Vollers SS, Condron MM, Straub E, Teplow DB. A Molecular Switch in Amyloid Assembly: Met35 and Amyloid -protein Oligomerization. Journal of the American Chemical Society. 2003, 125, 15359-15369.
27. Lashuel HA, Hartley D, Petre B, Walz T, Lansbury PT. Neurodegenerative Diseases, Amyloid Pores from Pathogenic Mutations. Nature. 2002, 418, 291.
a.C&EN: Science & Technology - What‘s Behind Amyloid Diseases? , By Sophie L. Wilkinson Chemical & Engineering News, 80 (32), August 12, 2002. http://pubs.acs.org/cen/science/8032/8032sci1.html
28. 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.
a. Science: Deadly Giveaway, Protein linked to Parkinson's disease squanders clearance molecules, By John R. Davenport . Science Magazine October 23, 2002. http://sageke.sciencemag.org/cgi/content/abstract/sageke;2002/42/nw145.
b. Focus: Enzyme Linked to Pathology of Parkinson’s Disease Appears Two-faced: Protein's Reckless Side May Lead to Deadly Pileups in the Cell. By Courtney Humphries, November 8, 2002. http://focus.hms.harvard.edu/2002/Nov8_2002/index.html
29. 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 Alzheimer’s disease. J. Biol. Chem. 2002, 277: 42881-42890.
30. Lashuel HA, Petre B, Wall, Simon M, Nowak RJ, Walz T, Lansbury PT. -Synuclein, Especially the Parkinson’s Disease-Associated Mutants, Form Pore-like Annular and Tubular Protofibrils. J. Mol. Biol. 2002 , 322, 5, 1089-1102.
31. 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.
32. Oza VB, Smith C, Raman P, Koepf EK,, Lashuel HA, Petrassi M, Chiang K, Powers ET, Sachettinni J, and Jeffery W. Kelly. J. Synthesis, structure, and activity of diclofenac analogues as transthyretin amyloid fibril formation inhibitors. Med. Chem., 2002, 45, 321-332.
33. 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.
34. Gingolani G, Lashuel HA, Gerace L, Müller CW. Nuclear import factors importin and importin undergo mutually induced conformational changes upon association. FEBS Letters, 2000, 484, 291-298.
35. Liu K, Cho HW, Lashuel , Kelly JW, Wemmer DE. A Glimpse of a Possible Amyloidogenic Intermediate of Transthyretin. Nature Structural Biology, 2000, 7, 754-757.
36. 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.
37. Atkins AR, Lashuel HA, Kelly JW, Edelman GW, Wright PE, Cunningham BA, Dyson J. Association between the first two Immunoglobulin-like domains of the Neural Cell Adhesion Molecule N-CAM. FEBS Letters, 1999, 451, 162-168.
38. Chitnumsub P, Fiori WR, Lashuel HA, Diaz H. Kelly JW. The Nucleation of Monomeric Parallel -Sheet-like Structures in Aqueous Solutions. Bioorganic & Medicinal Chemistry. 1999, 7, 1, 39-59.
39. 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.
40. Patricelli MP, Lashuel HA, Kelly JW, Cravatt BF. Comparative Characterization of Wild Type and Transmembrane Domain-Deleted Fatty Acid Amide Hydrolase: Identification of the Transmembrane Domain as a Site for Oligomerization. Biochemistry 1998 37, 15177-1518.
41. Xie Y, Lashuel HA, Miroy GJ, and Kelly JW. Efficient Refolding and Characterization of Recombinant Human Plasma Retinal-Binding Protein from Inclusion Bodies in E.coli. Protein Expression and Purification. 1998, 14, (1), 31-37.
42. Hengst L, Lashuel HA, Reed SI. One Molecule of p21Kip1Is Sufficient to Inhibit One CdK/Cyclin Complex. Genes & Development. 1998, 12, 3882-3888.
43. Peterson SA, Klabunde T, Lashuel HA, Purkey H, Sacchettini JC, Kelly JW. Inhibiting Transthyretin Conformational Changes that Lead to Amyloid Fibril Formation. Proceedings of the National Academy of Science. U.S.A. 1998, 95, 12956-12960.
44. Xiangang Z, Zhu H, Lashuel HA, Hu J. Probing the Oligomerization Properties of GCN4 Leucine Zipper e & g Position Mutants. Protein Science. 1997, 6, 2218-2226.
45. Colon W, Zhihong L, Lashuel HA, McCulloch J, McCutchen S, Miroy GJ, Peterson SA, Kelly JW. Transthyretin Conformational Changes Facilitate Misassembly into Amyloid: A New Therapeutic Strategy Based on Preventing the Amyloidogenic Conformational Changes. Advances in Protein Chemistry, “Protein Misassembly” 1997, 161-179. Edited by Ronald Wetzel, Academic Press.
46. 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.
47. 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, 15051-1505.
Meeting Reports:
1. Kimberly TW, Kovacs DM, Walsh D, Lashuel HA, Lemere CA. The 8th International Conference on Alzheimer’s Disease and Related Disorders. Amyloid, 2003, 10, 51-61.
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Patents
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1. Miroy GJ, Kelly JW, Lai Z, Lashuel HA, Petterson SA. Treatment of amyloid disease using amyloidogenic protein-stabilising 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 Alzheimer’s disease. WO2003053356-A; WO2003053356-A2; AU2002357911-A1; US2003187011-A1.
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Invited Talks
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2001
1. King Fahed University of Petroleum and Minerals, Department of Chemistry Seminar, Dhahran, Saudi Arabia, April, 2001.
2002
2. University of California San Francisco, “Physical Properties of Amyloid Diseases”, San Francisco, CA. December, 25-27 2002.
3. Parkinson’s Institute, “Protein Fibrillogenesis in Parkinson’s Disease”, Sunnyvale, CA.
December, 28 2002.
4. Massachusetts Institute of Technology, Department of Biology: “Structural Biology Seminar”, March, 18, 2002.
5. American Chemical Society National Meeting, “Structural and Mechanistic Aspects of Amyloid Fibril Formation” Orlando Florida, April, 7-11 2002.
6. FASEB Meeting,: “Amyloid and Other Abnormal Protein Processes”, Colorado, June, 15-20 2002.
7. Biogen,Inc, Cambridge, MA, September, 6th, 2002.
8. Protein Folding and Disease: The Horizon Symposia “ Protein Folding and Disease” organized by Nature Publishing Group and Aventis. Verona, Italy, October, 2-5th 2002.
9. Elan BioPharmaceuticals, San Francisco, CA, October 13, 2002.
10. RIKEN Brain Science Institute: The first international workshop of molecular neuropathology “Frontiers in Molecular Neuropathology” Japan, November, 27-29 2002.
2003
11. Boehringer Ingelheim Fonds Internalional Titisee Conferences “ Alzheimer’s and Parkinson’s Disease: From Basic Science to Therapeutic Treatment. Germany, Titise/Black Forest, March 19-23, 2003.
12. Third Multidisciplinary Workshop,: “Self-assembling Peptides & Protein Systems in Biology, Medicine and Engineering” Crete, Greece, August, 2003.
13. Lady Davis Institute for Medical Research, Montreal, Canada, August 27th, 2003.
14. Rensselaer Polytechnic Institute, Department of Chemistry Seminar Series. “Protein fibrillogenesis in Neurodegenerative Diseases: From Biophysics to Therapeutic Strategies. Albany, NY September 2nd, 2003.
15. University of Rhode Island's Department of Biomedical Sciences, Rhode Island, November 2003.
2004
16. 10th Neural Workshop Verbier, “Molecular, Cellular and Clinical Aspects of Neurodegenerative Diseases” Verbier, Switzerland, January, 2004.
17. Institute for Complex Adaptive Matter Workshop. Protein Misaggregation: from Biomolecules to Neurodegeneration. Boston, MA, February 9th- 11, 2004.
18. Washington University School of Medicine, St. Louis, Alzheimer’s disease research center seminar, April 20th, 2004.
19. Clark Universitty, Department of Chemistry and Biochemistry. Worcester, MA, April 28th, 2004.
20. King Faisal Specialist Hospital and Research Center, Ryiadh, Saudi Arabia, April 30th –May 5th.
21. 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
22. Netherlands Brain Institute, Amsterdam, Netherlands, June 4th, 2004.
23. Institut de Recerca Biomèdica de Barcelona, Barcelona, Spain, June 10-11th, 2004.
24. The Siwss Federal Institute of Technology (EPFL), Lausanne, Switzerland, June 7th-9th.
25. Summer Neuropeptide 2004 Conference, Miami, July 5-9, 2004.
26. Washington University School of Medicine, St. Louis, Department of Biochemistry seminar, July 23th, 2004.
27. FEBS research course "New molecular strategies to treat neurodegenerative diseases".
Ofir – Portugal, July 17-23, 2004.
28. University of Texas Health Science Center, San Antonio, Texas. Department of Biochemistry, July 25th, 2004.
2005
29. Ph.D. Course in Protein Fibrillation and Aggregation. Aalborg University, Denmark, May 17-20.
30. The Second Japan-Switzerland Workshop on Biomechanics "New Trends in Biomechanics: from Biomolecule to Tissue. Kyoto, Japan. September 12 -16, 2005.
31. University of Geneva, Department of Biochemistry and Structural Biology Seminar, Geneva, June 17th.
32. The 3rd Lemanic Neuroscience Conferente, Diablerets, Switzerland.
33. 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.
34. International Neuroscience conference in the United Arab Emirtaes, November 26-29, 2005.
35. FENS/HERTIE winter school. Neurodegenerative Aggregation Disorders: from genes to protein aggregation,neuronal dysfunction and experimental treatments. Kitzbuhel, Austria, December 2005.
36. The Second Japan-Switzerland Workshop on Biomechanics "New trends in Biomechanics: from biomolecule to tissue. Kyoto, Japan. September 12 –16.
2006
37. Novartis Pharmaceuticals, Basel, Switzerland. January 10th, 2006.
38. Biozentrum, University of Basel, January 24th, 2006.
39. 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.
40. The annual meeting of the German Society of Human Genetics, "Molecular mechanisms in Huntington disease protein misfolding", Heidelberg, Germany, March 8, 2006.
41. School of Sciences, Taiz University, Republic of Yemen, April 20th, 2006
42. International Conference “From Sold State to Biophysics III” Dubrovnik, Croatia, June 24-July 1st, 2006.
43. Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Göttingen, Germany, May 21, 2006.
44. Symposium on “Protein Transport, Synaptic Function and Neurodegenerative Diseases”. European Neuroscience Institute, Göttingen, Germany, Sep 3, 2006.
45. The European BioAlpine Convention, Grenoble- Keynote Speaker, France, October 6, 2006.
46. Department of Theoretical Biology, Peking University, Bejing, China, November 19-21st, 2006.
47. Visiting Professor, Universiti Teknologi Malaysia, Skudai, Johor, Malaysia, November 21-24, 2006.
2007
48. Keynote Speaker, Lake Geneva Innovation Society (LGIS) Gala Dinner, Geneva, Switzerland, January 23rd.
49. Verbier Neural Workshop. “Nutrition, Exercise and Neurodegenerative Diseases”, January 28-31st, 2007.
50. The Ringber Meeting 2007. “Molecular basis of toxic protein conformation”, Ringberg Castle, Bavaria, Germany, February 18-21st, 2007.
51. Wyeth Research, Neuroscience Discovery Research, Princeton, New Jersey, USA, March 1-2.
52. Weill Cornell Medical College, New York, USA, March 5th.
53. Banbury Center, Cold Spring Harbor "When is Amyloid Functional and When is Amyloidogenesis Pathological? New York, USA, March 11-14th.
54. Third meeting on the "Molecular Mechanisms of Neurodegeneration”, Milan, Italy, May 19-21, 2007.
55. New Frontiers in Basic and Clinical Research in Parkinson's disease and other synucleinopathies Queensland, Australia, July 5-6, 2007.
56. Protein Assembly in Materials, Biology, and Medicine, DIRECT IMPACT ON BIOLOGICAL NANOSCIENCES, Crete, Greece, Capsis Hotel, July 7-10.
57. FENS Summer School, Molecular Strategies for treating neurodegenerative diseases, July 8-15 in Ofir, Portugal
58. 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
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Associate Professor