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Dr Claire Thornton

Lecturer in Cell & Molecular Biology

Start date at Kings: 1/09/2012

Contact details:

Postal address:
Room 14
1st Floor
South Wing St Thomas'
St Thomas'
United Kingdom

Department

Clinical Academic Group

Research interests

Hypoxic ischaemic (HI) encephalopathy during birth results in neural cell death and the development of long term disabilities (motor/cognitive impairment etc). Although there is some immediate acute brain damage, the majority of cell death occurs with a delay post-HI. In infants and animal models of HI there is an initial depletion of ATP, phosphocreatine and glucose within the brain followed by a transient recovery (the “latent” phase). Subsequently, there is a secondary energy failure during which cell death is maximal. We and others have shown that HI triggers events such as NMDA/AMPA receptor activation, production of reactive oxygen species and increases in intracellular calcium.  Data from our lab and others strongly suggest that in response to these stimuli, the "tipping point" in commiting the cell to death is the degree of mitochondrial dysfunction they cause. As there is currently only one clinical intervention available to treat infants with term HI injury (therapeutic hypothermia, successful in 1 in every 7 babies), restoring mitochondrial health may provide a new avenue to address this urgent unmet need.

My research is focussed on the underlying mechanisms of cell death which result from hypoxic-ischaemic insult (HI) in the neonatal brain. Key molecules involved in apoptotic, necroptotic and mitophagic pathways are upregulated in response to HI. We are currently using in vitro and in vivo models of HI to investigate whether any of these targets offer "mitotherapeutic" potential to act as an adjunct to therapeutic hypothermia. 

 

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