Department: Comparative Biomedical Sciences

Campus: Camden

Research Groups: Brain Health and Behaviour, CPCS (Research Programme)

Claire Thornton leads the Neurocellular Stress group, focused on deciphering the molecular mechanisms underlying brain injury after metabolic and other stresses. Her research centres on understanding the consequences of pathological alterations in neuronal energy metabolism and mitochondrial function, with the ultimate aim of identifying novel targets for neurotherapeutic intervention. 

Following undergraduate Biological Sciences and postgraduate Human Molecular Genetics degrees, Claire Thornton completed her PhD at Imperial College with Prof David Carling (Imperial) and Dr Mike Snowden (GSK) in 1999 on the regulation of the mammalian cellular "fuel  gauge", AMPK. Claire then carried out postdoctoral research at University of California, San Francisco, working on neuronal signalling perturbed by drugs of addiction, with Prof Dorit Ron. She returned to the UK, continuing in the field of neuronal cell stress as an Investigator Scientist at the MRC Clinical Sciences Centre and, in 2007, was awarded a Research Into Ageing Fellowship to investigate the role of AMPK-mediated tau phosphorylation as an early event in Alzheimer’s disease. Claire subsequently took up a lectureship at King’s College London where she investigated the molecular basis of Perinatal Brain Injury in response to birth asphyxia, before being appointed as Senior Lecturer in Cell and Molecular Biology at the RVC in October 2018 focussing on neurocellular stress. Claire continues to work on cell death mechanisms in neonatal brain injury in response to a variety of stresses such as hypoxia-ischaemia, toxicant and pollution exposure.

Claire is a Fellow of the Higher Education Academy, and a member of the Biochemical Society, the British Neurosicence Association, the British Cell Biology Association and the Society for Neuroscience.

Claire's research interests centre on the molecular basis of neurocellular stress, and the impact of pathologies resulting in neural energy depletion. In particular, her research targets perturbations in mitochondrial dynamics affecting their fission, fusion and mitophagy with the ultimate aim of generating new targets for neuroprotective intervention. Currently, Claire's lab is focussed on understanding cellular energy impairment underlying the development of brain injury in babies following i) asphyxia during birth, ii) exposure to air pollution and iii) exposure to drugs of abuse.

Research in the Neurocellular Stress Group is supported by grants from the Medical Research Council, Action Medical Research and the Royal Society.

Morris RH, Counsell SJ, McGonnell IM and Thornton C. (2021) Early life exposure to air pollution impacts neuronal and glial cell function leading to impaired neurodevelopment Bioessays e2000288. doi: 10.1002/bies.202000288. Online ahead of print.

Thornton C, Grad E and Yaka R. The role of mitochondria in cocaine addiction (2021) Biochem J. 478(4):749-764. doi: 10.1042/BCJ20200615

Faccenda D, Gorini G, Jones A, Thornton C, Baracca A, Solaini G, Campanella M. (2021) The ATPase Inhibitory Factor 1 (IF 1) regulates the expression of the mitochondrial Ca2+ uniporter (MCU) via the AMPK/CREB pathway Biochim Biophys Acta Mol Cell Res. 1868(1):118860. doi: 10.1016/j.bbamcr.2020.118860.

Bingor A, Haham T, Thornton C, Stern-Bach Y and Yaka R (2020) Zeta Inhibitory Peptide (ZIP) attenuates learning and memory independent of PKMζ 1 by inducing NO-mediated downregulation of AMPA receptors Nat Commun 11, 3688 . 

Stolp HB, Fleiss B, Arai Y, Supramaniam V, Vontell R, Birtles S, Yates AG, Baburamani AA, Thornton C, Rutherford M, Edwards AD, Gressens P. (2019) Interneuron Development Is Disrupted in Preterm Brains With Diffuse White Matter Injury: Observations in Mouse and Human. Front Physiol. 10 955. doi: 10.3389

Vontell R, Supramaniam V, Davidson A, Thornton C, Marnerides A, Holder-Espinasse M, Lillis S, Yau M, Jansson M, Hagberg H and Rutherford M. (2019) Post-mortem Characterisation of a Case with an ACTG1 Variant, Agenesis of the Corpus Callosum and Neuronal Heterotopia. Front. Physiol.10:623

Nair S, Sobotka KS, Joshi P, Gressens P, Fleiss B, Thornton C, Mallard C and Hagberg H. (2019) Lipopolysaccharide-induced alteration of mitochondrial morphology induces a metabolic shift in microglia modulating the inflammatory response in vitro and in vivo Glia. 67(6):1047-1061 doi: 10.1002/glia.23587

Rocha-Ferreira E, Poupon L, Zelco A, Leverin A-L, Nair S, Jonsdottir A, Carlsson Y, Thornton C, Hagberg H and Rahim A. (2018) Neuroprotective exendin-4 enhances hypothermia therapy in a model of hypoxic-ischemic encephalopathy Brain 141 2925-2942

Kichev A, Baburamani AA, Vontell R, Gressens P, Burkly L, Thornton C and Hagberg H. (2018) TWEAK receptor deficiency has opposite effects on female and male mice subjected to neonatal hypoxia-ischemia. Front Neurol 9 230 doi: 10.3389/fneur.2018.00230

Stolp HB, Ball G, So P-W, Tournier J-D, Jones M, Thornton C and Edwards AD (2018) Voxel-wise comparisons of cellular microstructure and diffusion-MRI in mouse hippocampus using 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND) Sci Rep 8 4011-23 (corresponding author)

Koning G, Lyngfelt E, Svedin P, Leverin A-L, Jinnai M, Gressens P, Thornton C, Wang X, Mallard C and Hagberg H (2018) Magnesium sulphate induces preconditioning in preterm rodent models of cerebral hypoxia-ischemia. Int J Dev Neurosci 70 56-66 doi: 10.1016/j.ijdevneu.2018.01.002

Zhang X, Rocha-Ferreira E, Li T, Vontell R, Jabin D, Hua S, Zhou K, Nazmi A, Albertsson AM, Sobotka K, Ek J, Thornton C, Hagberg H, Mallard C, Leavenworth JW, Zhu C and Wang X (2017) γδT cells but not αβT cells contribute to sepsis-induced white matter injury and motor abnormalities in mice. J Neuroinflamm 14 255

Koning G, Leverin A-L, Nair S, Schwendimann L, Ek J, Carlsson Y, Gressens P, Thornton C, Wang X, Mallard C and Hagberg H (2017) Magnesium induces preconditioning of the neonatal brain via profound mitochondrial protection. J Cereb Blood Flow Metab doi: 10.1177/0271678X17746132

Kichev A, Eede P, Gressens P, Thornton C*, Hagberg H.* (2017) Implicating Receptor Activator of Nuclear Factor-κB (RANK)/RANK ligand (RANKL) signalling in microglial activation. Dev Neurosci  39 192-206

Baburamani AA, Sobotka KS, Vontell R, Mallard C, Supramaniam V, Gressens P, Thornton C, Hagberg H (2017) Effect of trp53 gene deficiency on brain injury after neonatal hypoxia-ischemia Oncotarget 8 12081-92

Baburamani AA, Hurling C, Stolp H, Sobotka K, Gressens P, Hagberg H and Thornton C (2015) Mitochondrial Optic Atrophy (OPA)1 processing is altered in response to neonatal hypoxic-ischaemic brain injury. Intl J Mol Sci 16, 22509-22526

Baburamani AA, Mayakuni Y, Vontell R, Supramaniam VG, Svedin P, Rutherford M, Gressens P, Mallard C, Takeda S, Thornton C* and Hagberg  H* (2015) Does caspase-6 have a role in perinatal brain injury? Dev Neurosci 37(4-5):321-37

Fleiss B, Chhor V, Rajudin N, Lebon S, Hagberg H, Gressens P* and Thornton C* (2015) The anti-inflammatory effects of the small molecule pifithrin-µ in BV2 microglia. Dev Neurosci 37(4-5):363-75

Rousset CI, Leiper FC, Kichev A, Gressens P, Carling D, Hagberg H and Thornton C. (2015) A dual role for AMP-activated protein kinase (AMPK) during neonatal hypoxic-ischemic injury in mice. J. Neurochem 133(2):242-52

Vontell R, Supramaniam VG, Wyatt-Ashmead J, Gressens P, Rutherford M, Hagberg H* and Thornton C* (2015) Cellular Mechanisms of Toll-Like Receptor-3 activation in Thalamus in Response to White Matter Injury in the Developing Brain. J Neuropathol Exp Neurol 74(3) 273-85

Kichev A, Rousset CI, Baburamani AA, Reynolds R, Levison S, Wood T, Gressens P,  Thornton C and Hagberg H. (2014) Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling and cell death in the immature central nervous system after hypoxia-ischemia and inflammation. J Biol Chem 289 9430-9

Nair S, Hagberg H, Krishnamurthy R, Thornton C and Mallard C. (2013) Death Associated Protein Kinases: molecular structure and brain injury. Intl J Mol Sci 14 13858-72

Järlestedt K, Rousset CI, Ståhlberg A, Sourkova H, Atkins AL, Thornton C, Barnum SR, Wetsel RA, Dragunow M, Pekny M, Mallard C, Hagberg H and Pekna M. (2013) Receptor for complement peptide C3a: a therapeutic target for neonatal hypoxic-ischemic brain injury. FASEB J 27 3797-804

Vontell R, Supramaniam V, Thornton C, Ashmead-Wyatt J, Rutherford M and Hagberg H. (2013) Toll-like Receptor 3 expression identified in glia and neurons in the developing brain alters in response to insult. Dev Neurosci 35 130-9

Thornton C, Bright NJ, Sastre M, Muckett, P and Carling D. (2011) AMPK is a tau kinase, activated in response to β-amyloid exposure. Biochem J. 434 503-12 

Thornton C, Sardini A and Carling D. (2008) Muscarinic receptor activation of AMP-activated Protein Kinase inhibits orexigenic neuropeptide expression. J. Biol. Chem. 283(25):17116-22

Bright, NJ, Carling D* and Thornton C.* (2008) Investigating the regulation of Brain Specific Kinases 1 and 2 by phosphorylation. J. Biol. Chem. 283(22):14946-54

Jurd R, Thornton C, Wang J, Luong K, Phamluong K, Kharazia V, Gibb SL and Ron D. (2008) Mind bomb-2 is an E3 ligase that ubiquitinates the NMDA receptor NR2B subunit in a phosphorylation-dependent manner. J. Biol. Chem. 283(1):301-10

Thornton C, Tang K-C, Phamluong K, Luong K, Vagts A, Nikanjam D, Yaka R, and Ron D. (2004) Spatial and temporal regulation of RACK1 function and NMDA receptor activity through WD40 motif-mediated dimerization. J. Biol. Chem. 279(30):31357-64

Thornton C, Yaka R, Dinh S, Ron D. (2003) H-Ras modulates N-methyl-D-aspartate receptor function via inhibition of Src tyrosine kinase activity. J. Biol. Chem. 278(26):23823-9

Yaka R, Thornton C, Vagts AJ, Phamluong K, Bonci A, Ron D. (2002) NMDA receptor function is regulated by the inhibitory scaffolding protein, RACK1. Proc. Natl. Acad. Sci. U S A. 99:5710-5.

Thornton C, Snowden MA, Carling D. (1998) Identification of a novel AMP-activated protein kinase beta subunit isoform that is highly expressed in skeletal muscle. J. Biol. Chem. 273(20):12443-50

 

Reviews

Poupon-Bejuit L, Rocha-Ferreira E, Thornton C, Hagberg H and Rahim AA. (2020) Neuroprotective effects of diabetes drugs for the treatment of neonatal hypoxia-ischemia encephalopathy. Front Cell Neurosci 14:112

Thornton C, Jones A, Nair S, Aabdien A, Mallard C and Hagberg H. (2018) Mitochondrial dynamics, mitophagy and biogenesis in neonatal hypoxic ischaemic brain injury FEBS Letters doi: 10.1002/1873-3468.12943

Thornton C, Baburamani AA, Kichev A and Hagberg H (2017) Oxidative stress and endoplasmic reticulum (ER) stress in the development of neonatal hypoxic-ischemic brain injury Biochem Soc Transactions 45(5) 1067-76

Leaw B, Nair S, Lim R, Thornton C, Mallard C and Hagberg H. (2017) Mitochondria, bioenergetics, and excitotoxicity: new therapeutic targets in perinatal brain injury Front Cell Neurosci doi: 10.3389/fncel.2017.00199.

Thornton C, Leaw B, Nair S, Mallard C, Jinnai M and Hagberg H. (2017) Cell Death in the Developing Brain after Hypoxia-Ischemia Front Cell Neurosci doi: 10.3389/fncel.2017.00248

Thornton C (2017) AMPK – keeping the (power)house in order Neuronal Signaling 1(2) NS20160020 Invited commentary

Thornton C and Hagberg H (2015) Role of mitochondria in apoptotic and necroptotic cell death in the developing brain Clin Chim Acta 451 (Part A) 35-38

Hagberg H, Mallard C, Rousset CI and Thornton C. (2014) Mitochondria: hub of injury responses in the developing brain. Lancet Neurology, 13(2) 217-32

Carling D, Thornton C, Woods A and Sanders M. (2012) AMP-activated protein kinase: new regulation, new roles? Biochem J 445 11-27

Rousset CI, Baburamani AA, Thornton C and Hagberg H. (2012) Mitochondria and Perinatal Brain Injury J. Matern-Fetal Neonatal Med 25 35-28

Thornton C, Rousset CI, Kichev A, Mayakuni Y, Vontell R, Baburamani AA, Fleiss B, Gressens P and Hagberg H. (2012) Molecular mechanisms of neonatal brain injury. Neurol Res Int 2012:506320

Bright NJ, Thornton C and Carling D. (2009) The regulation and function of mammalian AMPK-related kinases. Acta. Physiol. 196(1):15-26

Carling D, Woods A, Thornton C, Cheung PC, Smith FC, Ponticos M, Stein SC (1997) Molecular characterization of the AMP-activated protein kinase and its role in cellular metabolism. Biochem. Soc. Trans. 25(4):1224-8.

 

Book Chapters

Fleiss B, Thornton C and Gressens P (2017) Neurology: Neuroprotective Strategies in Neonatology (2nd Ed) in press

Thornton C and Hagberg H. Mechanisms of cell death in the developing brain in: Fetal and Neonatal Physiology, 5th Edition. Polin et al. (eds.). ISBN 9780323352147. Publ  Elsevier Publishing Company, New York 2016.

Claire is Year/Pathway lead for the MSci Biological Science / Bioveterinary Science course, running the MSci4 Research Skills module and overseeing the Extended Research Projects. Claire is also Deputy lead for the MRes programme and runs the BSc2 Brain Injury Group Project theme. Claire also regularly hosts undergraduate and postgraduate student research projects in her lab.

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