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Project Title:
The role of Signal Transducer and Activator of Transcription 3 (STAT3) in neuronal pathways of Neonatal Hypoxic Ischaemic Encephalopathy
Project description:
STAT3 plays a central role in the molecular cascade triggered by neonatal HI, leading to neural cell death. Deletion of STAT3 reduces the severity of HI-induced neonatal brain injury and STAT3 activation can be modulated via pharmacological inhibition of its phosphorylation via the Jak2 pathway. Pharmacological inhibition of STAT3 activation by preventing Tyr705 phosphorylation, using the Jak2/STAT3 inhibitor WP1066, selectively affects the transcription properties of pSTAT3, without an effect on the Ser727 phosphorylation site, thus avoiding inhibition of mito-STAT3. This prevents the detrimental effects of STAT3 activation while simultaneously preserving mitochondrial function. Combined treatment of mild TH and inhibition of STAT3 phosphorylation at Tyr705 will have additive protective effects in neonatal HI compared to TH alone.
Start Date
09/2019
Primary supervisor
Dr Mariya Hristova
Based at
86 - 96 Chenies Mews