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Corinne Lasmezas, Ph.D.

Professor
Department of Infectious Diseases
Florida Campus
lasmezas@scripps.edu
561-228-3456

Scripps Research Joint Appointments

Faculty, Graduate Program

Research Focus

Neurodegenerative diseases

Prion diseases are fatal neurodegenerative diseases affecting humans and animals. There is no cure for prion diseases. They are caused by an unconventional infectious agent called prion, which is thought to be composed mainly by a misfolded form of a host protein, the prion protein (PrP). In humans, prions cause Creutzfeldt-Jakob disease; in animals, scrapie has been known to ravage sheep flocks for two hundred years, and chronic wasting disease is of concern in the United States. The recent epidemic of bovine spongiform encephalopathy in the United Kingdom has caused major turmoil throughout Europe, and later, in other countries such as Japan, Canada and the United States, because the bovine prion disease is transmissible to humans causing variant Creutzfeldt-Jakob disease. The transmissibility of the latter by blood transfusion created a novel public health issue.

Recent years have witnessed major advances in our understanding of the role of the prion protein and other host factors in prion replication. Our aim now is to devise intervention strategies based on blocking the neurodegenerative process on one hand, and prion replication on the other hand. The latter is part of a drug discovery program that we are running in collaboration with the Scripps Florida Lead Identification Division.

Prion diseases belong to the same group of protein misfolding neurodegenerative diseases as Alzheimer, Parkinson, Huntington’s diseases, amyotrophic lateral sclerosis (ALS) and others. In all these diseases, a host protein misfolds, aggregates and becomes toxic to neurons. We use the prion protein as a model system and starting point to study the neurodegenerative mechanisms that cause these diseases. We aim to understand which form(s) of these culprit proteins cause the death of neurons, and to decipher the death program(s) that they trigger in order to devise neuroprotective strategies.

Education

M.S., Aeronautic and Space Medicine, University of Toulouse
D.V.M., Veterinary Medicine, University of Toulouse
M.S., Neurosciences, Pierre and Marie Curie University, Paris
Ph.D., Neurosciences, Pierre and Marie Curie University, Paris

Selected References

Lasmézas, C.I. and Zhou, M. Newly defined toxic alpha-helical prion protein monomer: implications for other neurodegenerative diseases? Expert Rev. Proteomics; 2012; 9(3): 233-5.

Zhou M., Ottenberg G., Sferrazza G.F., Lasmézas, C. I. Highly neurotoxic monomeric alpha-helical prion protein. Proc Natl Acad Sci USA: 2012:109(8): 3113-8.

Saa P., Sferrazza G.F., Ottenberg G., Oelschlegel A., Dorsey K., Lasmézas, C. I. Strain-specific role of RNAs in prion replication. J. Virol; 2012:86(19).

Karapetyan Y., Saa P., Mahal S., Sferrazza G., Sherman A., Salès N., Weissmann C. and. Lasmézas C. I. Prion strain discrimination based on rapid in vivo amplification and analysis by the cell panel assay.  PLoS ONE: 2009 :4(5) :e5730.

Simoneau S, Rezaei H, Salès N, Kaiser-Schulz G, Lefebvre-Roque M, Vidal C, Fournier JG, Comte J, Wopfner F, Grosclaude J, Schätzl H, Lasmézas CI. In vitro and in vivo neurotoxicity of prion protein oligomers. PLoS Pathog. 2007 Aug 31;3(8):e125.

Lasmézas, C. I., Comoy, E., Hawkins, S., Herzog, C., Mouthon, F., Konold, T., Auvre, F., Correia, E., Lescoutra-Etchegaray, N., Sales, N., Wells, G., Brown, P. & Deslys, J. P. Risk of oral infection with bovine spongiform encephalopathy agent in primates. Lancet 2005 ;365, 781-3.

Adjou, K. T., S. Simoneau, N. Salès, F. Lamoury, D. Dormont, D. Papy-Garcia, D. Barritault, J. P. Deslys, and Lasmézas C. I. A novel generation of heparan sulfate mimetics for the treatment of prion diseases. J Gen Virol 2003 84:2595-603.

Lasmézas C. I., Fournier J-G, Nouvel V., Boe H., Marcé D., Lamoury F., Kopp N., Hauw J-J, Ironside J., Bruce M., Dormont D. & Deslys J-P. Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt-Jakob Disease: Implications for human health. Proc Natl Acad Sci USA 2001 ; 98, 4142-4147

Haik S., Peyrin J-M, Lins L., Rosseneu M.Y., Brasseur R., Langeveld J.P., Tagliavini F., Deslys J-P, Lasmézas C.I. Dormont D. Neurotoxicity of the putative transmembrane domain of the prion protein. Neurobiology of Diseases; 2000; 7: 644-656.

Lasmézas C. I., Deslys JP, Robain O, Jaegly A., Beringue V., Peyrin J-M, Fournier J-G, Hauw J-J, Rossier J., Dormont D. Transmission of the BSE agent to mice in the absence of detectable abnormal prion protein. Science 1997;275: 402-405.

Lasmézas C. I., Deslys JP, Robain O, Demaimay, R., Adjour K.T., Lamoury F., Ironside J., Hauw J-J, Dormont D. BSE transmission to macaques. Nature 1996;381: 743-744.