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DR. CHRISTOPHER A. SHAW
Office Phone: 604-875-4111 ext. 68373
Lab Phone: 604-875-4111 ext. 68375
Fax: 604-875-4376
E-mail: cashawlab at gmail.com
Current research interests:
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.
References:
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, Pelech S, Ly PTT.
Paradoxical responses to neurotoxic glycosides: insights from
a cellular model of ALS-PDC. Neurobiology of Lipids. 8,1 (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).
Snyder RL, Cruz-Aguado R,
Sadilek M, Glasko D, Shaw C, Montine TJ. Lack of cerebral BMAA
in human cerebral cortex. Neurology. 72 (15):1360-1361. (2009).
Ly PTT, Pelech S, Shaw CA.
Cholesteryl glucoside stimulates activation of protein kinase B/Akt
in motor neuron-derived NSC34 cell line. Neurobiology of Lipids.
7, 4. (2008).
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).
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