Personal Statement
Pat is the Johnston Chair of Biochemistry, Professor of Cell Signalling and Head of the Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology. He obtained an undergraduate degree in Biochemistry at the University of Bristol, and completed his PhD with Sir Philip Cohen at the University of Dundee in 2000. After 4 years of postdoctoral research in the USA with the late Jim Maller, he set up his laboratory in the UK with an MRC Career Development Fellowship in 2005. His interests include all aspects of protein phosphorylation and sulfation, redox-based analysis of protein kinase and sulfotransferase regulation, pseudokinases and pseudoenzymes and kinome-wide mechanisms of acquired drug resistance in cells. He also teaches cell signalling, running modules explaining the biochemical mechanisms underpinning cell communication. In 2022, he spun-out the biotech company Sulantrix (www.sulantrix.com) from the University of Liverpool, with a goal of developing a new generation of anti-cancer agents targeting pseudoenzymes such as pseudokinases.

A 25 year timeline of research highlights:

1) Examining the temporal redox regulation of protein kinases and pseudokinases (2018-2024)
2) Evaluating regulatory mechanisms of the PKA signaling pathway (2016-2024)
3) Analysis of sulfotransferases: sulfoproteomics and regulation of protein and glycan sulfation (2017-2024)
4) Kinome-wide responses to clinical drugs in human breast, lung and uveal cancer models (2017-2024)
5) Drug-resistant Aurora, Polo-like and Mps1 kinases for inhibitor and PROTAC target-validation (2010-2015)
6) Conserved rate-limiting roles for protein kinases in the human cell cycle (2005/2008/2017/2018)
7) Purification and characterisation of TPX2, a physiological activator of Aurora A (2003)
8) Cellular ‘target-validation’ of p38 MAPK inhibitors using chemical genetics (2000)
9) Initial description of paradoxical activation of RAF kinases by chemical RAF inhibitors (1999)
10) Co-discovery of the 'gatekeeper' residue in p38 MAPKs and RAF (1998)

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 and 15 PhD students and with our international collaborators, we are developing new methods for quantitative analysis of cell signaling, notably the proteins that control covalent modifications of proteins. My work spans co-discovery of the protein kinase gatekeeper residue (a major determinant of drug sensitivity and resistance) and the first use of drug-resistant kinase alleles for inhibitor target validation, through to our recent analysis of pseudokinases, redox phosphoproteomes and combinatorial Tyr-based signaling in model systems. In 2018, we began a programme of work to analyse how redox biology interfaces with cell signalling, and disclosed conserved mechanisms of Ser/Thr protein kinase regulation that are likely to be relevant to multiple antioxidant stress responses in eukaryotic cells. Happily, many Cys residues in proteins also provide unique handles for the design of next-generation covalent drugs.