Photo of Professor Pat Eyers

Professor Pat Eyers BSc/PhD

Johnston Chair of Biochemistry and Head of Department Biochemistry, Cell and Systems Biology

Research

Research Overview

I am the recipient of >£4 million in personal and >£12 million in collaborative funding at the University of Liverpool in the last decade. I have trained 12 PDRAs (2 currently active) and 15 PhD students (3 currently active) and with our international collaborators, we are developing new methods for quantitative analysis of cell signaling, notably the enzymes that control covalent modifications of proteins. My work spans co-discovery of the protein kinase gatekeeper residue (a major determinant of drug-resistance) and the first use of drug-resistant kinase alleles for inhibitor target validation, through to our recent analysis of redox phosphoproteomes in model systems. In 2018, we began a programme of work to analyse the redox biology of cell signalling , and recently disclosed conserved mechanisms of Ser/Thr protein kinase regulation that are likely to be relevant to multiple antioxidant stress responses in eukaryotic cells.

Cell Signalling, Protein phosphorylation, sulfation and chemical biology

Tribbles pseudokinases come of age
Tribbles pseudokinases come of age

• Chemical Biology, protein kinase regulation, kinase and sulfotransferase inhibitors: resistance and escape mechanisms in human cancer cells and identification of new and ‘re-purpoused’ small molecule inhibitors to target unstudied and ‘drug-resistant' kinases
• Liverpool Enzyme Screening and Assay Facility; Academic Lead and Director: screening of protein kinases and small molecule modulators using microfluidic-based technology. In collaboration with academia and pharmaceutical companies
• Molecular analysis of human protein pseudokinases and members of the 'dark' kinome, which contains many new drug targets. Employing chemical genetics to uncover the effects of small molecules on (pseudo)kinase function in vitro and in vivo
• Protein Kinase Biophysics: NMR, Ion Mobility and cryo-EM analysis of differentially activated and drug-resistant Mps1, Aurora A and pseudokinase proteins in complex with regulators and ligands. Design of new reporter assays to measure ligand occupancy
• Transcriptional Kinome-wide analysis of cellular signalling networks in human cancer cells. In particular, kinome 'rewiring' in response to clinical compounds

Protein and glycan sulfation

Back-to-back papers analysing sulfation mechanisms
Back-to-back papers analysing sulfation mechanisms

We are investigating how sulfation-dependent signalling occurs in vertebrate cells, and how this controls a number of key intracellular and extracellular signalling events.

Research Grants

Bench Fees for Halah Shabeeb H Almutairi (201703482)

KING SAUD UNIVERSITY (SAUDI ARABIA)

September 2023 - August 2027

Understanding NETosis – from triggers of chronic inflammation to inhibitors

ROYAL SOCIETY

February 2024 - January 2029

Bench Fees for Jamilah Mohammed D Alshehri (201534553)

KING SAUD UNIVERSITY (SAUDI ARABIA)

May 2022 - April 2026

A new mechanism of redox regulation in Ser/Thr protein kinases

BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL

March 2023 - February 2026

Neutrophil extracellular traps (NETs) as a therapeutic target for the treatment of auto-immune inflammatory disease

VERSUS ARTHRITIS (UK)

September 2022 - November 2023

A data analytics framework for mining the dark kinome

NATIONAL INSTITUTES OF HEALTH (USA)

May 2019 - April 2022

Non-canonical protein phosphorylation in human cancer cells

NORTH WEST CANCER RESEARCH INCORPORATING CLATTERBRIDGE CANCER RESEARCH (UK)

June 2018 - January 2022

Studentship for Emma Fairweather

ASTRAZENECA LIMITED (UK)

October 2017 - September 2021

Understanding the complexity of post-translation modifications by enhancing UK capability for top-down proteomics

BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL, KEELE UNIVERSITY (UK), UNIVERSITY OF LEEDS (UK)

June 2017 - June 2018

3-O-sulfated heparan sulfate translocation in altered membrane biology: A new strategy for early population screening and halting Alzheimer’s neurodegeneration (ArrestAD)

EUROPEAN COMMISSION

January 2017 - May 2022

Therapeutic relevance of crosstalk in the Aurora A and PLK4 signalling modules

NORTH WEST CANCER RESEARCH INCORPORATING CLATTERBRIDGE CANCER RESEARCH (UK)

October 2017 - September 2020

Increasing Industry Engagement and Open Innovation in Health and Life Sciences - Proximity to Discovery Award

MEDICAL RESEARCH COUNCIL

March 2016 - August 2017

New tools and resources to evaluate biological sulphation

BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL

October 2016 - March 2018

A streamlined approach for the analysis of drug-resistant protein kinase alleles

NORTH WEST CANCER RESEARCH INCORPORATING CLATTERBRIDGE CANCER RESEARCH (UK)

January 2016 - December 2017

Investigating in vivo resistance mechanisms to MEK inhibitors in uveal melanoma to enable novel combinatorial therapies.

NORTH WEST CANCER RESEARCH INCORPORATING CLATTERBRIDGE CANCER RESEARCH (UK)

March 2016 - May 2019

Role of serine protease activity in the pathogenesis of muscular dystrophy

MUSCULAR DYSTROPHY ASSOCIATION USA)

September 2015 - January 2019

Application of advanced MS instrumentation to protein ligand binding and PTM characterisation

BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL

January 2015 - January 2016

Kinome-wide analysis of KRASand MYC driven cancer cell models exposed to clinical kinase and bromodomain inhibitors

NORTH WEST CANCER RESEARCH INCORPORATING CLATTERBRIDGE CANCER RESEARCH (UK)

September 2014 - August 2017