Phone: 604 875-4111 ext. 68373
Web pages: N/A
My laboratory's key focus over the last few years has been on the unusual neurological disease of Guam and the Western Pacific, ALS-parkinsonism dementia complex (ALS-PDC). I view this disease as a kind of neurological Rosetta Stone able to unlock some of the key questions in neurological disease research. For example: what are the causes of ALS, Parkinson's, and Alzheimer's and what are the pre-clinical stages of each? Our approach has been to create an in vivo animal model in which we can look at behavioural changes in motor and cognitive functions, as well as systems, cellular and biochemical modifications as the disease process emerges over time. We have identified a novel class of neurotoxins in the course of our initial studies and are now beginning to understand the toxic mechanisms of action that lead to the death of neurons in the spinal cord and brain. The overall goal of this work is to identify key etiological factors involved in sporadic neurological disease and the early stages of the disease process. From the first could come effective prophylaxis; from the latter, early phase treatment before irreversible damage to the CNS has been done.
A second theme to our work is to seek potential therapeutic agents for existing neurological disease states using the above, and other, animal models. In particular, we are focusing our attention on progranulin, a neuroepithelial growth factor, and on a class of molecules called ginsenosides. Preliminary data with progranulin suggests that the molecule can exert powerful neuroprotective effects and perhaps even reverse early phase neurodegeneration.
The last aspect of our work, and one that is still emerging, is to look at the potential for compounds such as aluminum to be neurotoxic. We are interested in the types of aluminum compounds that can cause neurodegeneration, their route of administration, the impact of dose and duration, and the crucial but largely unexplored aspects of age and sex. These studies are just beginning, but show great promise to help us understand the origin of neurological disorders as diverse as autism spectrum disorder and Alzheimer's disease.
Shaw CA, Li D, Tomljenovic L. Are there negative CNS impacts of aluminum adjuvants in vaccines and immunotherapy? Immunotherapy. 6 (10):1055-1071. (2014).
Van Kampen, J.M., Baranowski, D.C., Shaw, C.A., and D.G Kay. Panax ginseng is neuroprotective in a novel progressive model of Parkinson’s disease. Exp Gerontol, 50(2014):95-105. (2014).
Shaw CA, Sheth S, Li D, Tomljenovic L. Etiology of autism spectrum disorders: Genes, environment, or both? OA Autism. 10:2(2):11. (2014).
Shaw CA, Tomljenovic L. Aluminum in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and autoimmunity. Immunol Res. DOI 10.1007/s12026-013-8403-1. (2013).
Shaw CA, Li Y, Tomljenovic L. Administration of aluminum to neonatal mice in vaccine in vaccine-relevant amounts is associated with adverse long term neurological outcomes. J Inorg Chem. http://dx.doi.org/10.1016/j.jinorgbio.2013.07.022. (2013).
Tomljenovic L, Shaw CA. Death after quadrivalent human papillomavirus (HPV) vaccination: causal or coincidental? Pharma Reg Affairs. S12:001. Doi:10.4172/2167-7689.S12-001. (2012).
Tomljenovic L, Shaw CA. Mechanisms of aluminum adjuvant toxicity and autoimmunity in pediatric populations. Lupus. 21:223-230. (2012)
Lee G, Shaw AC. Early exposure to environmental toxin contributes to neuronal vulnerability and axonal pathology in a model of familial ALS. Neuroscience Medicine. Doi:10.4236/nm.2012. (2012).
Tomljenovic L and Shaw CA. No autoimmune safety signal after vaccination with quadrivalent HPV vaccine Gardasil? J Internal Medicine. Doi.10.1111/j.1365-2796.2012.025551.x. (2012).
Tomljenovic L and Shaw CA. Do aluminum vaccine adjuvants contribute to the rising prevalence of autism? J Inorg Biochem. 105(11):1489-99. (2011).
Panov A, Kubalik N, Brooks BR, and Shaw CA. In vitro effects of cholesterol β-D-glucoside, cholesterol and cycad glucosides on respiration and reactive oxygen species generation in brain mitochondria. J. Membrane Biol. DOI 10:1007/s00232- 10-9307-7. (2010).
Shen W-B, McDowell KA, Siebert AA, Clark SM, Dugger NV, Valentino KM, Jinnah A, Sztalryd C, Fishman PS, Shaw CA, Jafri MS, and Yarowsky PJ. Environmental neurotoxin-induced progressive model of parkinsonism in rats. Annals of Neurology. 68(1):70-80. (2010).
Tasker RA, Adams-Marriott AL, Shaw CA. New animal models of progressive neurodegeneration: tools for identifying presymptomatic therapeutic targets. The EMPA Journal. (2010).
Ryan CL, Baranowski DC, Chitramuthu BP, Malik S, Li Z, Cao M, Minotti S, D Durham HD, Kay DG, Shaw CA, Bennett HPJ, Bateman A. Progranulin is expressed within motor neurons and promotes neuronal cell survival. BMC Neuroscience. doi.10.1186/1471-2202-10-130. (2009).
Shaw CA and Petrik MS. Aluminum hydroxide injections lead to motor deficits and motor neuron degeneration. J Inorganic Biochem. 103 (11): 1555-62. (2009).
Shaw CA Höglinger GU. Neurodegenerative diseases: neurotoxins as sufficient etiologic agents? J Neuromolecular Medicine. 10(1): 1-9. (2008).
Tabata RC, Wilson JMB, Van Kampen JM, Cashman N, Shaw CA. Dietary sterol glucosides are neurotoxic to motor neurons and induce an ALS-PDC phenotype. J Neuromolecular Medicine. 10(1): 24-39. (2008).
Petrik MS, Wilson JMB, Grant SC, Blackband SJ, Tabata RC, Shan X, Krieger C, Shaw CA. Magnetic resonance microscopy and immunohistochemistry of the CNS of the mutant SOD murine model of ALS reveals widespread neural deficits. J Neuromolecular Medicine. 9(3): 216-229, (2007).
Ly PTT, Singh S, Shaw CA. Novel environmental toxins: steryl glucosides as a potential etiological factor for age-related neurodegenerative diseases. J Neurosci. Res. 85(2): 231-237. (2007).
Petrik MS, Wong MC, Tabata RC, Garry RF, Shaw CA. Aluminum adjuvant linked to Gulf War illness induces motor neuron death in mice. J Neuromolecular Medicine 9: 83-100. (2007).
Wilson, J.M.B., Khabazian, I., Wong, M.C., Seyedalikhani, A., Bains, J.S., Pasqualotto, B.A., Williams, D.E., Andersen, R.J., Simpson, R.J., Smith, R., Craig, U.K., Kurland, L.T., and Shaw, C.A. Behavioral and neurological correlates of ALS-parkinsonism dementia complex in adult mice fed washed cycad flour. J. Neuromol. Med. 1(3): 207-222. (2002).
Khabazian, I., Bains, J. S., Williams, D.E., Cheung, J., Wilson, J.M.B., Pasqualotto, B.A., Pelech, S.L., Andersen, R.J., Wang, Y.-T., Liu, L., Nagai, A., Kim, S.U., Craig, U.-K., Shaw, C.A. Isolation of various forms of sterol b-d-glucoside from the seeds of cycas circinalis: neurotoxicity and implications for ALS-PDC. J. Neurochem. 82: 1-13. (2002).