MD, PhD, FRCSC
Suneil Kalia, MD, PhD, FRCSC is a scientist at Toronto Western Research Institute and Associate Professor in the Division of Neurosurgery at the University of Toronto.
His laboratory research focuses on understanding how abnormal protein homeostasis leads to neurodegeneration.
As a neurosurgeon, he specializes in deep brain stimulation for the surgical management of movement disorders including Parkinson’s disease.
My laboratory focuses on understanding how chaperone molecules fail to maintain protein homeostasis in Parkinson's disease and other neurodegenerative disorders with the goal of developing novel molecular therapeutics for the treatment of these disorders.
Parkinson’s disease (PD) is a disabling movement disorder that affects between 1-3% of the Canadian population over the age of 65. Poor handling and elimination of misfolded proteins has been identified as central in the molecular pathogenesis of PD. A special class of proteins within the cell called “chaperones” is responsible for refolding misfolded or damaged proteins. If the chaperone system cannot adequately deal with these misfolded proteins, they are targeted to specialized disposal systems in the cell including the ubiquitin-proteasome system and the autophagy-lysosomal system. Together these pathways are critical to maintain protein quality control within a cell. If they are dysfunctional or overwhelmed then neurodegeneration ensues.
Our current work is aimed at:
- Understanding how chaperone molecules fail to maintain adequate protein quality control in PD and other neurodegenerative disorders;
- Dissecting molecular pathways that contribute to aberrant protein disposal via the proteasome and lysosomal systems in PD; and,
- Developing innovative methods to target and regulate these protein quality control pathways in PD and other neurodegenerative disorders.
Our ultimate goal is to find ways to mitigate the loss of neurons in the brain to be able to slow or even halt the progression of PD and other neurodegenerative disorders.
Beilina A, Rudenko IN, Kaganovich A, Civiero L, Chau H, Kalia SK et al. Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease. Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2626-31.
Sidiropoulos C, Masani K, Mestre T, Milosevic M, Poon YY, Fallis M et al. Spinal cord stimulation for gait impairment in spinocerebellar ataxia 7. J Neurol. 2014 Mar;261(3):570-4.
Strauss I, Kalia SK, Lozano AM. Where are we with surgical therapies for Parkinson's disease? Parkinsonism Relat Disord. 2014 Jan;20 Suppl 1:S187-91.
Dimant H, Kalia SK, Kalia LV, Zhu LN, Kibuuka L, Ebrahimi-Fakhari D et al. Direct detection of alpha synuclein oligomers in vivo. Acta Neuropathol Commun. 2013 May 9;1(1):6.
Kalia SK, Sankar T, Lozano AM. Deep brain stimulation for Parkinson's disease and other movement disorders. Curr Opin Neurol. 2013 Aug;26(4):374-80.
Kalia SK, Lozano AM. Parkinson disease: Neurostimulation in PD--benefit of early surgery revealed. Nat Rev Neurol. 2013 May;9(5):244-5.
Sidiropoulos C, Hutchison W, Mestre T, Moro E, Prescott IA et al. Bilateral pallidal stimulation for Wilson's disease. Mov Disord. 2013 Aug;28(9):1292-5.
Kalia LV, Kalia SK, McLean PJ, Lozano AM, Lang AE. α-Synuclein oligomers and clinical implications for Parkinson disease. Ann Neurol. 2013 Feb;73(2):155-69.
Kalia LV, Kalia SK, Chau H, Lozano AM, Hyman BT, McLean PJ. Ubiquitinylation of α-synuclein by carboxyl terminus Hsp70-interacting protein (CHIP) is regulated by Bcl-2-associated athanogene 5 (BAG5). PLoS One. 2011 Feb 16;6(2):e14695.
Kalia SK, Kalia LV, McLean PJ. Molecular chaperones as rational drug targets for Parkinson's disease therapeutics. CNS Neurol Disord Drug Targets. 2010 Dec;9(6):741-53.
Kim RH, Smith PD, Aleyasin H, Hayley S, Mount MP, Pownall S, Wakeham A et al. Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress. Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5215-20.
Kalia SK, Lee S, Smith PD, Liu L, Crocker SJ, Thorarinsdottir TE, Glover JR, Fon EA, Park DS, Lozano AM. BAG5 inhibits parkin and enhances dopaminergic neuron degeneration. Neuron. 2004 Dec 16;44(6):931-45.
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