Position:
Professor
Division:
Neurology
Research Sumary:

I have made many contributions to understanding of prion diseases for over 20 years, significantly including the discovery that the normal cellular isoform of the prion protein participates in cell activation (Cashman et al, Cell 1990) and lymphoid differentiation (Dodelet and Cashman, Blood 1998). These and other papers have been considered foundational in the new science of prion neuroimmunology, and have also been cited by scientists and policy makers as evidence for the prion infectablity of peripheral lymphoid and bone marrow cells.  More recently, I have identified an immunological epitope unique to the disease-associated isoform of the prion protein, with potential for use in non-invasive diagnosis and treatment of the prion disorders (Paramithiotis et al, Nature Medicine 2003; Cashman and Caughey, Nature Reviews in Drug Discovery 2004; Griffin and Cashman Expert Opinion on Biological Therapeutics 2006). Other recent prion work includes the identification of a cell surface receptor for these proteins (patent pending), copolymer-based therapies for prion disease (patent awarded), a prion peptide experimental system for studying amyloid formation (Zou et al, Europ Biochem 2001), an enhanced in vitro prion protein conversion system (Zou and Cashman, J Biol Chem 2002; patent pending), and the development of a novel method for detecting aggregated misfolded proteins, including prions, named Epitope Protection (patent pending). As a clinical neurologist concerned with the public health impact of newly emerging prion diseases, I have published numerous well-cited medical articles on this subject (e.g., Cashman CMAJ 1997; Coulthart and Cashman CMAJ 2001). I co-founded in 1998 the Canadian CJD Surveillance System, and I have I have made many contributions to understanding of prion diseases for over 20 years, significantly including the discovery that the normal cellular isoform of the prion protein participates in cell activation (Cashman et al, Cell 1990) and lymphoid differentiation (Dodelet and Cashman, Blood 1998). These and other papers have been considered foundational in the new science of prion neuroimmunology, and have also been cited by scientists and policy makers as evidence for the prion infectablity of peripheral lymphoid and bone marrow cells.  More recently, I have identified an immunological epitope unique to the disease-associated isoform of the prion protein, with potential for use in non-invasive diagnosis and treatment of the prion disorders (Paramithiotis et al, Nature Medicine 2003; Cashman and Caughey, Nature Reviews in Drug Discovery 2004; Griffin and Cashman Expert Opinion on Biological Therapeutics 2006). Other recent prion work includes the identification of a cell surface receptor for these proteins (patent pending), copolymer-based therapies for prion disease (patent awarded), a prion peptide experimental system for studying amyloid formation (Zou et al, Europ Biochem 2001), an enhanced in vitro prion protein conversion system (Zou and Cashman, J Biol Chem 2002; patent pending), and the development of a novel method for detecting aggregated misfolded proteins, including prions, named Epitope Protection (patent pending). As a clinical neurologist concerned with the public health impact of newly emerging prion diseases, I have published numerous well-cited medical articles on this subject (e.g., Cashman CMAJ 1997; Coulthart and Cashman CMAJ 2001). I co-founded in 1998 the Canadian CJD Surveillance System, and I have served as an expert for the Canadian government and international industry on these diseases (e.g., the “”Cashman Report”” on risks of transmission of prion disease through blood and blood products for Health Canada 1999, McDonald’s Corporation Scientific Advisory Committee since 2001).  I am the Scientific Director of PrioNet Canada, a Network of Centres of Excellence awarded in November 2005. Caprion Pharmaceuticals in Montreal was initially founded in 1998 to commercialize my prion discoveries. Amorfix Life Sciences was founded in 2004 to commercialize my work in detection and treatment of protein misfolding diseases, including prion disorders and other neurodegenerative diseases. I am Chief Scientific Officer of Amorfix, which became public on the TSX-V exchange in October 2005, and now has a market capitalization of ~CAD 50 M. Both Caprion and Amorfix technology emerged from programs originally funded by CIHR.

 

Education:
Bowdoin College, Physics, B.A.
University of Massachusetts Medical School, MD
Recent Publications:

•Kalra S, Vitale A, Cashman NR, Jirsch J, Genge A, Arnold DL. MR spectroscopic biomarkers of neuronal integrity predict survival in ALS and can contribute to diagnosis. J Neurol Neurosurg Psychiatry. 77:1253-5, 2006.
•Griffin JK, Terry LA, Jackman R, Yousefi M, Cashman NR. Decreased cell surface prion protein in mouse models of prion disease. Neuroreport 18:1-6, 2007.
•Li L, Coulthart MB, Balachandran A, Chakrabartty A, Cashman NR. Species barriers for chronic wasting disease by in vitro conversion of prion protein. Biochem Biophys Res Commun 364(4): 796-800, 2007.
•Rakhit R, Robertson J, Vande Velde C, Horne P, Ruth DM, Griffin J, Cleveland DW, Cashman NR, Chakrabartty A. An immunological epitope selective for pathologically misfolded SOD1 in ALS. Nat Med 13 (6), 754-9, 2007.
•”Cashman N, Tan LY, Krieger C, Mädler B, Mackay A, Mackenzie I, Benny B, Nantel S, Fabros M, Shinobu L, Yousefi M, Eisen A.Pilot study of granulocyte colony
•stimulating factor (G-CSF)-mobilized peripheral blood stem cells in amyotrophic
•lateral sclerosis (ALS). Muscle Nerve 37:620-5, 2008.”
•”Rutherford NJ, Zhang YJ, Baker M, Gass JM, Finch NA, Xu YF, Stewart H, Kelley BJ, Kuntz K, Crook RJ, Sreedharan J, Vance C, Sorenson E, Lippa C, Bigio EH, Geschwind DH, Knopman DS, Mitsumoto H, Petersen RC, Cashman NR, Hutton M,
•Shaw CE, Boylan KB, Boeve B, Graff-Radford NR, Wszolek ZK, Caselli RJ, Dickson DW, Mackenzie IR, Petrucelli L, Rademakers R. Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis. PLoS Genet. 4(9) e1000193, 2008.”
•Tabata RC, Wilson JM, Ly P, Zwiegers P, Kwok D, Van Kampen JM, Cashman N, Shaw CA. Chronic Exposure to Dietary Sterol Glucosides is Neurotoxic to Motor Neurons and Induces an ALS-PDC Phenotype. Neuromolecular Med. 10:24-39, 2008.
•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 U S A. 105:4022-7, 2008.
•Yuan J, Dong Z, Guo JP, McGeehan J, Xiao X, Wang J, Cali I, McGeer PL, Cashman NR, Bessen R, Surewicz WK, Kneale G, Petersen RB, Gambetti P, Zou WQ. Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prions. Cell Mol Life Sci. 2008 65:631-43, 2008.
•Cashman N, Darshan S, Krewski D, Tyshenko MG.Prion research in perspective. Preface. J Toxicol Environ Health A. 2009;72(17):999.
•Hedlin PD, Cashman NR, Li L, Gupta J, Babiuk LA, Potter AA, Griebel P, Napper S. Design and delivery of a cryptic PrP(C) epitope for induction of PrP(Sc)-specific antibody responses. Vaccine. 2009.
•Wong M, Toth J, Haney S, Toth, Tyshenko MG, Darshan S, Krewski D, Leighton FA, Westaway D, Moore SS, Ricketts M, Cashman NR. PrioNet Canada:  A Network of Centres of Excellence for Research into Prions and Prion Diseases. Journal of Toxiocology and Environmental Health 2009;72(17):1000-7.
•Li L, Guest W, Huang A, Plotkin S, Cashman NR. Immunological mimicry of PrPC-PrPSc interactions: Antibody-induced PrP misfolding. Protein Engineering, Design and Selection, Protein Eng Des Sel. 2009 Aug;22(8):523-9.
•Haddon JD,  Hughes MR, Antignano F, David Westaway  D, Cashman NR, McNagny KM. Prion protein is expressed on mast cells and is released upon their activation. The Journal of Infectious Diseases, 2009 Sep 1;200(5):827-31.
•Guest W, Cashman NR, Plotkin SS. Electrostatics in the Stability and Misfolding of the Prion Protein: Salt Bridges, Self-Energy, and Solvation. Biochemistry and Cell Biology, in press.
•Li L, Napper S, Cashman NR. Immunotherapy for TSE diseases: opportunities and obstacles. Immunotherapy, in press.
•Rademakers R, Stewart H, DeJesus-Hernandez M, Krieger C, Graff-Radford n, Fabros M, Briemberg H, Cashman N, Eisen A, Mackenzie I.  FUS gene mutations in familial and sporadic amyotrophic lateral sclerosis.  Muscle Nerve 2010;42(2):170-6.