Cashman, Neil

Dr. Cashman is a Clinician-Scientist Professor of Medicine (Neurology) at the UBC DMCBH, where he has held a Tier-1 Canada Research Chair in Neurodegeneration and Protein Misfolding Diseases (2005-2019). He is also Founder and Chief Scientific Officer of ProMIS Neurosciences, which translates his lab’s therapeutics and diagnostics in protein misfolding diseases. Dr. Cashman’s research focus is elucidating the structure and pathogenicity of proteins which misfold in neurodegeneration, starting with the prion protein (Cell 1990). He has developed novel strategies for immunotherapeutic intervention in these diseases, which are specifically directed at peptide motifs exposed by protein misfolding, but inaccessible in native structures. This notion of targeting a propagating and toxic conformation while sparing normal proteins was pioneered by his studies of prion-specific epitopes (Nat Med 2003; Nat Rev Drug Discov 2004). With Dr. Steven Plotkin of UBC Department of Physics and Astronomy, he has also identified Aβ oligomer-specific conformational epitopes as safe targets for Alzheimer’s disease immunotherapies that spare monomers and fibrils (ACS Chem Neurosci 2018; Sci Rep 2019). Dr. Cashman’s laboratory program in ALS is focused on propagated misfolding of the proteins SOD1, TDP43, and FUS. He established that SOD1 misfolding is transmitted between SOD1 molecules, and within and between cells in a prion-like manner, providing novel targets for immunotherapeutics (PNAS 2011; PNAS 2014). His lab has also discovered that TDP43 and FUS pathology induce cross-seeding of SOD1 misfolding, which then acquires the prion-like in vivo activity to confer on SOD1 molecules in neighboring cells (Sci Rep 2016), an example of the TDP43/FUS “pathological interactome.”