Janice Robertson

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Research synopsis

Amyotrophic Lateral Sclerosis (ALS), commonly known as Lou Gehrig's disease, is a fatal, adult-onset neurodegenerative disease that primarily targets the motor neurons responsible for voluntary muscle movements, such as for walking, talking , swallowing and breathing.

Disease starts as a mild muscle weakness that progresses to complete paralysis and eventual death, typically due to respiratory failure, within 2-5 years from onset. There is no known cure or effective treatment.

Approximately 5-10% of ALS cases are familial (fALS) with the remainder ocurring sporadically (sALS).

We study the major genes associated with the disease, including superxoide dismutase-1 (SOD1); TAR DNA Binding Protein (TDP-43); Fused in Sarcoma (FUS); and C9ORF72. In particular, we use a multidisciplinary approach to understand the molecular mechanisms by which these genes cause the disease. 

This involves studies of protein folding, cell and molecular biology, and generation and characterization of transgenic mouse models of the disease. 

Importantly, we have extensive links with the ALS Clinic run by Dr Lorne Zinman at Sunnybrook Health Sciences Centre, where 200-250 new cases of ALS are diagnosed each year.

Together with Dr Ekaterina Rogaeva (Geneticist) and Dr's Julia Keith and Juan Bilbao (Neuropathologists), we have established a clinical database and collection of blood, CSF and tissue for a comprehensive study of the disease.   

Selected publications

Liu H-N, Tjostheim S, DaSilva K, Taylor D, Zhao B, Rakhit R, Brown M, Chakrabartty A, McLaurin J and Robertson J. Targeting of Monomer/Misfolded SOD1 as a Therapeutic Strategy for ALS. J. Neurosci., 32(26):8791-9. (2012)

Xi Z, Zinman L,. Hazrati LN, Fornazzari L, Villagra R, Rojas-Garcia R, Clarimón J, Mayeux R,  Robertson J, St George-Hyslop P, & Rogaeva E. Investigation of C9orf72 in four neurodegenerative disorders. Archive of Neurology (in press)

Xiao S, Sanelli T, Dib S, Sheps D, Findlater J, Bilbao J, Keith J, Zinman L, Rogaeva E, Robertson J.  RNA Targets of TDP-43 identified by UV-CLIP are deregulated in ALS. Mol. Cell. Neurosci. 47:167-80 (2011)

Swarup, V., Phaneuf, D., Bareil, C., Robertson, J., Rouleau GA., Kriz J and Julien, J.P. Pathological hallmarks of ALS/FTLD in transgenic mice produced with genomic fragments encoding wild-type or mutant forms of human TDP-43. Brain 134:2610-26 (2011)

McLean, J. and Robertson, J  Isoform-specific expression and ratio changes accompany oxidant-induced peripherin aggregation in a neuroblastoma cell line. Brain Research 1442:57-65 (2011)

Robertson J, Bilbao J, Zinman L, Hazrati LN, Tokuhiro S, Sato C, Moreno D, Strome R, Mackenzie IR, Rogaeva E. A novel double mutation in FUS gene causing sporadic ALS. Neurobiology of Aging 32 553.e27–553.e3. (2011)

McLean J, Liu HN, Miletic D, Weng YC, Rogaeva E, Zinman L, Kriz J and Robertson J. Distinct biochemical signatures characterize peripherin isoform expression in both traumatic neuronal injury and motor neuron disease. J. Neurochem.114(4):117-92 (2010)

Kerman, A., Liu, H-N., Croul, S., Bilbao, J., Rogaeva, E., Zinman, L., Robertson, J., Chakrabartty, A. In vivo confirmation of SOD1 and other inclusion-forming proteins in ALS. Accepted Acta Neuropathol. 119(3):335-44 (2010)

Liu, H-N., Sanelli, T., Horne, P., Pioro, E.P., Strong, M.J., Rogaeva, E., Bilbao, J., Zinman, L. and Robertson, J.  Lack of evidence of monomer/misfolded SOD1 in sporadic ALS. Ann. Neurol., 66:75-80 (2009)

Zinman, L.H., Liu, H-N., Sato, C., Wakutani, Y., Marvelle, A., Moreno, D., Morrison, K.E., Mohlke, K.L., Bilbao, J. Robertson, J. and Rogaeva, E. A mechanism for low penetrance in an ALS family with a novel SOD1 deletion. Neurology 2:1153-9 (2009)

Xiao, S., Tjostheim, S, Sanelli, T., McLean, J., Horne, P., Fan, Y., Ravits, J., Strong, M.J. and Robertson, J. An aggregate-inducing peripherin isoform generated through intron retention is upregulated in amyotrophic lateral sclerosis and associated with disease pathology.  J. Neurosci., 28 (8): 1833-1840. (2008)

McLean, J., Xiao, S., Miyazaki, K., and Robertson, J. A novel peripherin isoform generated by alternative translation is required for normal filament network formation. J Neurochem., 104:1663-73. (2008)

Sanelli, T., Xiao S., Horne, P., Bilbao, J., Zinman, L. and Robertson, J. Evidence that TDP-43 is not the major ubiquitinated target within the pathogenic inclusions of ALS.  J. Neuropathol. Exp. Neurol., 66 (12): 1147-1153. (2007)

Rakhit, R., Robertson, J., C. Vande Velde, P. Horne, D.M. Ruth, J. Griffin, D.W. Cleveland, N.R. Cashman and A. Charkrabartty. (2007) An Imunological Epitope Selective for Pathological Monomer-Misfolded SOD1 in ALS. Nat. Med., 13:754-9. (2007)

Robertson, J., T. Sanelli, S. Xiao, Y.C. Wen, P. Horne, R. Hammond, E. Pioro, M.J. Strong. (2007) Lack of TDP-43 Abnormalities in mutant SOD1 transgenic mice shows disparity with ALS. Neurosci. Letts., 420:128-32. (2007)