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Identification of cisplatin-induced pro-inflammatory pathways in children that cause the development of pain in adults S&T17

  • School: School of Science and Technology
  • Study mode(s): Full-time / Part-time
  • Starting: 2022
  • Funding: UK student / EU student (non-UK) / International student (non-EU) / Fully-funded

Overview

NTU's Fully-funded PhD Studentship Scheme 2022

Project ID: S&T17

Advancement in medical research has led to an increased understanding and early diagnosis of childhood cancer, which has led to greater numbers of children now reaching adulthood (84%  5yr survivorship). However, clinically there are a number of side-effects due to their platinum-based cancer treatment that hinders a patients quality of life. Platinum-based chemotherapy induces vascular toxicity and tissue inflammation leading to pathological events that are implicated in major comorbidities including chronic pain and kidney disease. This effects a  significant proportions of adult survivors, with ~50% highlighting pain as a side-effect of their treatment. The symptom is progressive in nature and gets increasingly prominent years 10-plus years post-treatment. Although clinically well defined, the mechanisms that underpin vascular disease and peripheral painful neuropathies are poorly outlined and understood.

Cisplatin clearly causes profound adaption in the sensory neural network signalling in infants post-treatment, that effects sensory development into adulthood. Our studies have shown that tropomyosin receptor kinase A (TrkA) is activated in adults post early life exposure to cisplatin, a platinum-based chemotherapeutic agent. TrkA is a neuroinflammatory signalling protein that we believe is the axis of chronic pain manifestation in childhood cancer survivors. We have shown that cisplatin induced peripheral vascular inflammation through endothelial cell damage, causes the microvascular network around neurons to become more permeable facilitating inflammatory cell influx to the affected area, thereby sensitising the neuronal tissue through inflammatory mediator production.

We know that sensory neural tissues are shaped by intrinsic and extrinsic childhood experiences to form our unique individualised pain perception. It is therefore, the focus of this PhD will be to identify the cisplatin-induced changes in developmental trajectory of the sensory neural circuitry of pain perception in adulthood. Experimental design will incorporate an integrative approach to the problem using in vivo, in vitro and bioinformatics methodologies to identify key pathways that facilitate cross-talk between monocytes, endothelial cells and neurons. Methodologies will include rodent models, primary cell culture, nociceptive behavioural assays, confocal imaging, FACS analysis, biochemical assays, ELISA,  genomic and transcriptome bioinformatics and proteomics approaches to elucidate the impact of cisplatin upon neural developmental pathways. The ultimate aim is to inform therapeutic intervention strategies and identify novel therapeutic markers and targets for future treatment of peripheral neuropathies.

School strategic research priority

The theme aligns with the Centre for Health, Ageing and Understanding Disease.

Entry qualifications

For the eligibility criteria, visit our studentship application page.

How to apply

For guidance and to make an application, please visit our studentship application page. The application deadline is Friday 7 January 2022.

Fees and funding

This is part of NTU's 2022 fully-funded PhD Studentship Scheme.

Guidance and support

Download our full applicant guidance notes for more information.

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