I was a medical trainee from China and joined the Wellcome Centre for Mitochondrial Research at Newcastle University in 2015 to pursue a PhD with Dr Amy Reeve and Professor Sir Doug Turnbull. My main motivation stems from the patients I have encountered as a doctor and wanting to gain a further understanding into neurodegenerative diseases. My PhD project focused on the response of human substantia nigra neurons to mitochondrial dysfunction. I achieved my PhD in June 2019, and stayed in the Centre as a post-doctoral scientist to continue investigating the consequence of mitochondrial dysfunction in neurodegeneration.
Can pathways which control mitochondrial genesis and distribution reveal biomarkers for Parkinson’s Disease?
Principal Investigator: Dr Amy Reeve
Other staff members involved: Prof Sir Doug Turnbull
Mitochondrial dysfunction is important in the pathogenesis of both inherited and acquired Parkinson’s disease (PD). Such changes are well documented in the neurons of the substantia nigra (SN) and are highly likely to contribute to the neuronal death observed in patients with PD. Similar defects of mitochondrial dysfunction are seen in the substantial nigra of patients with inherited mitochondrial disease but no neuronal loss is observed. The aim of this work is (1) to determine the mechanisms protecting SN neurons in the brains of patients with inherited mitochondrial disease by comparison with the changes seen in brain tissue from patients with PD. (2) to identify new biomarkers and therapeutic avenues for patients with PD by using mass cytometric technology.
Sponsor/funder: Michael J Fox Foundation
Chen C, Turnbull DM, Reeve AK. Mitochondrial Dysfunction in Parkinson’s Disease—Cause or Consequence?. Biology. 2019 Jun;8(2):38.
Vincent AE, Rosa HS, Pabis K, Lawless C, Chen C, Grünewald A, Rygiel KA, Rocha MC, Reeve AK, Falkous G, Perissi V, White K, Davey T, Petrof BJ, Sayer AA, Cooper C, Deehan D, Taylor RW, Turnbull DM, Picard M. Sub-cellular origin of mtDNA deletions in human skeletal muscle. Ann Neurol. 2018 Jul 16. doi:10.1002/ana.25288.
Reeve AK, Grady JP, Cosgrave EM, Bennison E, Chen C, Hepplewhite PD, Morris CM. Mitochondrial dysfunction within the synapses of substantia nigra neurons in Parkinson’s disease. NPJ Parkinsons Dis. 2018 Mar 26;4:9. doi:10.1038/s41531-018-0044-6.
Ye Q, Chen C, Si E, Cai Y, Wang J, Huang W, Li D, Wang Y, Chen X. Mitochondrial Effects of PGC-1alpha Silencing in MPP(+) Treated Human SH-SY5Y Neuroblastoma Cells. Front Mol Neurosci. 2017 May 29;10:164. doi:10.3389/fnmol.2017.00164.
Ye Q, Huang W, Li D, Si E, Wang J, Wang Y, Chen C, Chen X. Overexpression of PGC-1α Influences Mitochondrial Signal Transduction of Dopaminergic Neurons. Mol Neurobiol. 2016 Aug;53(6):3756-3770. doi: 10.1007/s12035-015-9299-7.