Professor Neil Cashman, a Canadian leader in neurodegenerative diseases, was recruited to UBC from Toronto to establish a program of research into protein misfolding diseases such as amyotrophic lateral sclerosis (ALS). He is director of the new Vancouver Coastal Health ALS Centre, which is focused on research and treatment of the disease.
ALS is a progressive neuromuscular disease that eventually paralyzes limbs and muscles of speech, swallowing and respiration. There are about 2,500 Canadians living with ALS, for which there is no cure and only limited treatment.
Protein misfolding also plays a role in Alzheimerís and Parkinsonís diseases and it is implicated in prion (infectious protein) diseases such as mad cow disease and similar human illnesses, such as Creutzfeldt-Jakob Disease (CJD).
Symptoms of CJD include anxiety, depression, withdrawal and behavioural changes. The disease progresses to include motor difficulties, involuntary movements and mental deterioration. Patients may live for only about one year after onset of† symptoms.
Proteins, the fundamental component of living cells, are made up of long chains of amino acids which loop or fold about each other in a specific three-dimensional structure. Misfolded proteins can cause disease in surrounding cells.
Dr. Cashmanís research labs at the Brain Research Centre at UBC Hospital and at the UBC Life Sciences Institute are the first labs west of Ontario dedicated to investigating misfolding diseases.
Paramithiotis E, Pinard M, Lawton T, LaBoissiere S, Leathers VL, Zou W-Q, Estey LA., Kondejewski LH, Francoeur GP, Papadopoulos M, Haghighat A, Spatz SJ, Tonelli Q, Chakrabartty A, Cashman NR. A prion protein epitope selective for the pathologically misfolded conformation. Nature Med, 9:893-899, 2003.
Cashman NR and Caughey B. Prion diseases--close to effective therapy? Nature Reviews in Drug Discovery. 2004 Oct;3(10):874-84.
Rakhit R, Robertson J, Vande Velde C, Horne P, Ruth DM, Griffin J, Cleveland DW, Cashman NR, Chakrabartty A. An immunological epitope selective for pathological monomer-misfolded SOD1 in ALS. Nature Med 2007 Jun;13(6):754-9.
Vande Velde C, Miller TM, Cashman NR, Cleveland DW. Selective association of misfolded ALS- linked mutant SOD1 with the cytoplasmic face of mitochondria. Proc Natl Acad Sci 2008 Feb 22.
Khan MQ, Sweeting B, Mulligan VK, Arslan PE, Cashman NR, Pai EF, Chakrabartty A.† Prion disease susceptibility is affected by ?-structure folding propensity and local side-chain interactions in PrP. Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19808-13.
Grad LI, Guest WC, Yanai A, Pokrishevsky E, O'Neill MA, Gibbs E, Semenchenko V, Yousefi M, Wishart DS, Plotkin SS, Cashman NR. Intermolecular transmission of superoxide dismutase 1 misfolding in living cells. Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16398-403.
Guest WC, Silverman JM, Pokrishevsky E, O'Neill MA, Grad LI, Cashman NR. Generalization of the prion hypothesis to other neurodegenerative diseases: an imperfect fit. Journal of Toxicology and Environmental Health. Part A. 74(22-24):1433-59, 2011.
Pokrishevsky E, Grad LI, Makenzie I, Cashman NR. Aberrant Localization of FUS and TDP43 is Associated with Misfolding of SOD1 in Amyotrophic Lateral Sclerosis. PLoS One. 2012;7(4):e35050.
Dr. Neil Cashman is a neurologist-neuroscientist working in neurodegeneration and neuroimmunology. His special areas of work are the amyloid encephalopathies, such as the prion illnesses and Alzheimer's disease, and motor neuron diseases, particularly amyotrophic lateral sclerosis.
He was raised in the Boston area, and trained in Worcester (University of Massachusetts Medical School), San Francisco (Children's Hospital of San Francisco), Paris (HŰpital Necker), and Chicago (University of Chicago). He joined the McGill Neurology and Immunology faculties in 1986, and accepted the Diener Professorship of Neurodegenerative Diseases at the University of Toronto Department of Medicine (Neurology) in 1998. In July 2005, he was appointed Professor of Medicine at the University of British Columbia, where he holds the Canada Research Chair in Neurodegeneration and Protein Misfolding Diseases. He is Scientific Director to PrioNet Canada, a Network of Centres of Excellence focused on basic and applied research in the transmissible spongiform encephalopathies. He is Founder and Scientific Advisor to Caprion Pharmaceuticals, a Montreal biotechnology company since 1998 (now Thallion), and he is Founder and Chief Scientific Officer of Amorfix Life Sciences since 2005, two companies developed to commercialize his research on diagnostics and therapeutics of neurodegenerative diseases.
He is the author of over 300 publications, and provides expertise and guidance to numerous scientific, medical, and governmental committees related to his research interests. He has received peer-reviewed salary support without interruption since 1986. Special honors received over the decade include his tenure of the Diener Chair of Neurodegenerative Diseases at University of Toronto's Centre for Research in Neurodegenerative Diseases, the Jonas Salk Prize for "a lifetime of outstanding contributions to basic biomedical research," his Tier 1 Canada Research Chair in at the University of British Columbia, and his election to the Canadian Academy of Health Sciences.