Impact

Our research impacts on society by:

  • Identifying novel (protein) targets against which therapeutics can be developed.
  • Improving patient diagnosis and disease classification through the identification of molecules that are changed during disease.
  • Improving understanding of the mechanisms of therapeutic side-effects and drug-resistance.
  • Developing biomaterials to aid in cell-to-cell communication or tissue regeneration following injury.

Case studies

Developing ‘magic bullets’ for studying kinases and human diseases

(BBSRC, MRC and North West Cancer Research)

The regulation of protein function by ‘post-translational’ modifications, particularly an enzyme process called phosphorylation, lies at the heart of cellular signalling, but goes wrong in many human diseases.  The protein kinase superfamily is the 3rd largest human gene family, containing over 500 separate kinase proteins whose job is to control whether, and how, cells live and die. Unfortunately, only a small proportion of protein kinases have been studied in any biochemical detail, despite evidence that the majority of kinases can cause, or go on to support, key human diseases such as infection, inflammation and cancer.  The good news is that because of their specific 3D structure, protein kinases are highly attractive for drug discovery. Excitingly, around 30 ‘kinase inhibitors’ have been approved for clinical use, where their impact is enormous, ranging from hard-to-treat lung and skin cancer therapy through to life-changing effects in many leukaemia patients.

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At the University of Liverpool, we are working with collaborators worldwide to study a group of human kinases that have, until now, received relatively little attention as drug targets. This is because we don’t yet understand what they do in the body or how they cause diseases when they go wrong. Our work involves some rather special kinases, called ‘pseudokinases’, to reflect the fact that they were originally thought to be ‘zombie-like’ dead proteins. However, the research groups of Patrick Eyers and Claire Eyers are working out new ways to interrogate the function of conventional protein kinases and their unusual pseudokinases cousins, many of which have now been shown to have very important biological functions. Our ultimate goal is to develop new techniques to study all kinases, and to discover, or repurpose, drugs that can prevent kinases and pseudokinases from causing disease. This work will be important to help improve ‘personalised medicine’, by cataloguing how protein pseudokinases really work, and to ensure that the human patients receive the most appropriate targeted ‘kinase inhibitor’ therapies.


Biomarkers for the targeting of therapy in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, inflammatory arthritis that affects more than 0.5 million people in the UK, causing not only disability, but also premature death. The aim of management is to supress underlying inflammation, initially with inexpensive Disease Modifying anti-Rheumatic Drugs (DMARDs), escalating to expensive biologic agents, typified by Tumour Necrosis Factor inhibitors (TNFis), when disease suppression is not achieved. Whilst biologics are generally efficacious, each is unpredictably ineffective in up to 40% of patients – wasting NHS resources and potentially harming patients. Identification of biomarkers to predict response to a biologic is urgently needed for effective targeting of therapy, efficient utilisation of resource and maximal benefit for patients.

Rheumatoid arthritis (RA) is a chronic, inflammatory arthritis that affects more than 0.5 million people in the UK, causing not only disability, but also premature death. The aim of management is to supress underlying inflammation, initially with inexpensive Disease Modifying anti-Rheumatic Drugs (DMARDs), escalating to expensive biologic agents, typified by Tumour Necrosis Factor inhibitors (TNFis), when disease suppression is not achieved. Whilst biologics are generally efficacious, each is unpredictably ineffective in up to 40% of patients – wasting NHS resources and potentially harming patients. Identification of biomarkers to predict response to a biologic is urgently needed for effective targeting of therapy, efficient utilisation of resource and maximal benefit for patients.