My research interest is to understand the fundamental mechanisms of mitochondrial dynamics and movement in brain ageing and disease.

Honors & Awards

  • Glenn Foundation for Medical Research Postdoctoral Fellowships in Aging Research, AFAR (2019-2020)
  • Research Grant, Wellcome trust (2016)
  • PhD studentship, Parkinson's UK (2012-2015)

Professional Education

  • Master of Science, University College London (2012)
  • Doctor of Philosophy, University College London (2017)
  • MD, Harbin Medical University, Medicine (2010)

Stanford Advisors

All Publications

  • Miro1 Marks Parkinson's Disease Subset and Miro1 Reducer Rescues Neuron Loss in Parkinson's Models. Cell metabolism Hsieh, C. H., Li, L. n., Vanhauwaert, R. n., Nguyen, K. T., Davis, M. D., Bu, G. n., Wszolek, Z. K., Wang, X. n. 2019


    The identification of molecular targets and pharmacodynamic markers for Parkinson's disease (PD) will empower more effective clinical management and experimental therapies. Miro1 is localized on the mitochondrial surface and mediates mitochondrial motility. Miro1 is removed from depolarized mitochondria to facilitate their clearance via mitophagy. Here, we explore the clinical utility of Miro1 for detecting PD and for gauging potential treatments. We measure the Miro1 response to mitochondrial depolarization using biochemical assays in skin fibroblasts from a broad spectrum of PD patients and discover that more than 94% of the patients' fibroblast cell lines fail to remove Miro1 following depolarization. We identify a small molecule that can repair this defect of Miro1 in PD fibroblasts. Treating patient-derived neurons and fly models with this compound rescues the locomotor deficits and dopaminergic neurodegeneration. Our results indicate that tracking this Miro1 marker and engaging in Miro1-based therapies could open new avenues to personalized medicine.

    View details for DOI 10.1016/j.cmet.2019.08.023

    View details for PubMedID 31564441

  • A Drosophila Model of Neuronopathic Gaucher Disease Demonstrates Lysosomal-Autophagic Defects and Altered mTOR Signalling and Is Functionally Rescued by Rapamycin JOURNAL OF NEUROSCIENCE Kinghorn, K. J., Groenke, S., Castillo-Quan, J. I., Woodling, N. S., Li, L., Sirka, E., Gegg, M., Mills, K., Hardy, J., Bjedov, I., Partridge, L. 2016; 36 (46): 11654-11670
  • Increased Glucose Transport into Neurons Rescues Aß Toxicity in Drosophila. Current biology Niccoli, T., Cabecinha, M., Tillmann, A., Kerr, F., Wong, C. T., Cardenes, D., Vincent, A. J., Bettedi, L., Li, L., Grönke, S., Dols, J., Partridge, L. 2016; 26 (17): 2291-2300


    Glucose hypometabolism is a prominent feature of the brains of patients with Alzheimer's disease (AD). Disease progression is associated with a reduction in glucose transporters in both neurons and endothelial cells of the blood-brain barrier. However, whether increasing glucose transport into either of these cell types offers therapeutic potential remains unknown. Using an adult-onset Drosophila model of Aβ (amyloid beta) toxicity, we show that genetic overexpression of a glucose transporter, specifically in neurons, rescues lifespan, behavioral phenotypes, and neuronal morphology. This amelioration of Aβ toxicity is associated with a reduction in the protein levels of the unfolded protein response (UPR) negative master regulator Grp78 and an increase in the UPR. We further demonstrate that genetic downregulation of Grp78 activity also protects against Aβ toxicity, confirming a causal effect of its alteration on AD-related pathology. Metformin, a drug that stimulates glucose uptake in cells, mimicked these effects, with a concomitant reduction in Grp78 levels and rescue of the shortened lifespan and climbing defects of Aβ-expressing flies. Our findings demonstrate a protective effect of increased neuronal uptake of glucose against Aβ toxicity and highlight Grp78 as a novel therapeutic target for the treatment of AD.

    View details for DOI 10.1016/j.cub.2016.07.017

    View details for PubMedID 27524482

    View details for PubMedCentralID PMC5026704

  • Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis CELL REPORTS Castillo-Quan, J. I., Li, L., Kinghorn, K. J., Ivanov, D. K., Tain, L. S., Slack, C., Kerr, F., Nespital, T., Thornton, J., Hardy, J., Bjedov, I., Partridge, L. 2016; 15 (3): 638-650


    The quest to extend healthspan via pharmacological means is becoming increasingly urgent, both from a health and economic perspective. Here we show that lithium, a drug approved for human use, promotes longevity and healthspan. We demonstrate that lithium extends lifespan in female and male Drosophila, when administered throughout adulthood or only later in life. The life-extending mechanism involves the inhibition of glycogen synthase kinase-3 (GSK-3) and activation of the transcription factor nuclear factor erythroid 2-related factor (NRF-2). Combining genetic loss of the NRF-2 repressor Kelch-like ECH-associated protein 1 (Keap1) with lithium treatment revealed that high levels of NRF-2 activation conferred stress resistance, while low levels additionally promoted longevity. The discovery of GSK-3 as a therapeutic target for aging will likely lead to more effective treatments that can modulate mammalian aging and further improve health in later life.

    View details for DOI 10.1016/j.celrep.2016.03.041

    View details for Web of Science ID 000374498900018

    View details for PubMedID 27068460

    View details for PubMedCentralID PMC4850359

  • Loss of PLA2G6 leads to elevated mitochondrial lipid peroxidation and mitochondrial dysfunction BRAIN Kinghorn, K. J., Castillo-Quan, J. I., Bartolome, F., Angelova, P. R., Li, L., Pope, S., Cocheme, H. M., Khan, S., Asghari, S., Bhatia, K. P., Hardy, J., Abramov, A. Y., Partridge, L. 2015; 138: 1801-1816


    The PLA2G6 gene encodes a group VIA calcium-independent phospholipase A2 beta enzyme that selectively hydrolyses glycerophospholipids to release free fatty acids. Mutations in PLA2G6 have been associated with disorders such as infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation type II and Karak syndrome. More recently, PLA2G6 was identified as the causative gene in a subgroup of patients with autosomal recessive early-onset dystonia-parkinsonism. Neuropathological examination revealed widespread Lewy body pathology and the accumulation of hyperphosphorylated tau, supporting a link between PLA2G6 mutations and parkinsonian disorders. Here we show that knockout of the Drosophila homologue of the PLA2G6 gene, iPLA2-VIA, results in reduced survival, locomotor deficits and organismal hypersensitivity to oxidative stress. Furthermore, we demonstrate that loss of iPLA2-VIA function leads to a number of mitochondrial abnormalities, including mitochondrial respiratory chain dysfunction, reduced ATP synthesis and abnormal mitochondrial morphology. Moreover, we show that loss of iPLA2-VIA is strongly associated with increased lipid peroxidation levels. We confirmed our findings using cultured fibroblasts taken from two patients with mutations in the PLA2G6 gene. Similar abnormalities were seen including elevated mitochondrial lipid peroxidation and mitochondrial membrane defects, as well as raised levels of cytoplasmic and mitochondrial reactive oxygen species. Finally, we demonstrated that deuterated polyunsaturated fatty acids, which inhibit lipid peroxidation, were able to partially rescue the locomotor abnormalities seen in aged flies lacking iPLA2-VIA gene function, and restore mitochondrial membrane potential in fibroblasts from patients with PLA2G6 mutations. Taken together, our findings demonstrate that loss of normal PLA2G6 gene activity leads to lipid peroxidation, mitochondrial dysfunction and subsequent mitochondrial membrane abnormalities. Furthermore we show that the iPLA2-VIA knockout fly model provides a useful platform for the further study of PLA2G6-associated neurodegeneration.

    View details for DOI 10.1093/brain/awv132

    View details for Web of Science ID 000358536600015

    View details for PubMedID 26001724

    View details for PubMedCentralID PMC4559908