Research
Development and application of mass spectrometry-based strategies to understand protein modification in health and disease
The major theme of my research career has been the development and application of biochemical and biophysical (mass spectrometry, ion mobility) techniques to study cellular signal transduction and post-translational modifications (PTMs), particularly protein phosphorylation, on a global level. Identification of PTMs ultimately leads to better understanding, and thus the ability to model, cell signalling systems. This is particularly pertinent as we try to define how changes in protein modification and cell signalling drives cellular ageing and the onset/progression of diseases. My research interests include the application of MS-based techniques to understand proteins and their modifications in a quantitative manner, both at the peptide and protein level, particularly to better understand the roles of combinatorial protein modifications. We also apply structural mass spectrometry (native IM-MS) to correlate changes in site-specific protein modification with protein conformational dynamics, complex formation and ligand (small molecule, DNA) binding.
I am currently funded by CRUK, NWCR, BBSRC and Unilever, and have been involved in a number of large-scale cross-disciplinary BBSRC (LOLA, SABR) and EU-funded projects, including:
i) absolute quantification of the complete proteome of S. cerevisiae (i.e. defining protein copy number per cell), and assessment of changes in protein cohorts under conditions of stress;
ii) in-depth characterisation of stimulation-dependent changes in the modification status of the NFκB transcription factor p65 in a temporal manner. By applying standard peptide-based quantitative phopshoproteomics, native structural mass spectrometry and novel strategies for intact protein (top down) proteomics that are currently being developed in my group, we are investigate the combinatorial roles of multiple modifications on individual NF-kB proteins as a function of disease (cancer) status and in response to stress stimuli;
iii) screening for cancer-associated changes in the serum glycome by developing novel MS-based methodology for capture and analysis of glycans, glycosylated proteins and glycan binding proteins using self-assembled monolayers;
iv) expanding the landscape of protein phosphorylation in human cells, having developed analytical strategies that allow sites of phosphorylation on non typical amino acids residues (e.g. His, Asp, Glu, Lys, Arg) to be defined.
Research grants
An Integrated, Physiologically Based, Multiscale Platform to Humanise Preclinical Assessment of Fetal Drug Exposure and Toxicity During Pregnancy
WELLCOME TRUST (UK)
January 2024 - December 2031
Glycan profiling of immunoglobulin-complement immune complexes in IgA mediated glomerulonephritis: The GlyCAN study
KIDNEY RESEARCH UK (UK)
July 2023 - June 2028
Analysis of biomarkers to complement wearable technology
DEFENCE SCIENCE & TECHNOLOGY LABORATORY (UK)
February 2023 - September 2025
Increasing capabilities for robust high-throughput clinical proteomics within the Centre for Proteome Research at the University of Liverpool
MEDICAL RESEARCH COUNCIL
November 2022 - March 2023
Structure and signalling in ALK fusion protein compartments
MEDICAL RESEARCH COUNCIL
March 2023 - February 2026
A new mechanism of redox regulation in Ser/Thr protein kinases
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
March 2023 - February 2026
IgA Vasculitis: Do N-glycans play a role in pathogenesis
THE UK VASCULITIS TRUST (UK)
April 2022 - March 2023
Enhancing research culture funding from Research England
RESEARCH ENGLAND (UK)
December 2021 - March 2022
A cellenONE BSC to enhance UK capability for single-cell proteomics
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
July 2022 - July 2023
University of Liverpool Translational Institutional Partnership (TRAP)
WELLCOME TRUST (UK)
February 2021 - February 2024
Dietary Optimisation for Male Fertilisation Success and Healthy Reproductive Ageing
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
January 2022 - January 2026
COVID-19: Molecular mapping of SARS-Cov2 and the host response with multiomics mass spectrometry to stratify disease outcomes for therapeutic and diagnostic interventions.
UK RESEARCH AND INNOVATION
October 2020 - April 2022
PhosphoX-db: A web-based bioinformatics platform for studying non-canonical phosphorylation
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
September 2018 - June 2020
Non-canonical protein phosphorylation in human cancer cells
NORTH WEST CANCER RESEARCH INCORPORATING CLATTERBRIDGE CANCER RESEARCH (UK)
June 2018 - January 2022
Unilever Case Award for Maximilian Harris
UNILEVER PLC (UK)
October 2017 - January 2022
Analysis of Mucin Interactions
UNILEVER PLC (UK)
October 2017 - December 2017
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
NF-κB regulated signalling pathways that control tumourigenesis and the response to cancer therapy
CANCER RESEARCH UK (UK)
July 2016 - June 2021
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
Assay Development Platforms
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
February 2015 - November 2016
The PPP-labels software for quantitative proteomics
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
September 2014 - September 2015
Dynamics and function of the NF-kappaB signalling system
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
May 2013 - April 2014
Systems biology analysis of biological timers and inflammation
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
May 2013 - April 2018
A critical evaluation of the top 3 method for proteome-wide label-free quantification
BRITISH MASS SPECTROMETRY SOCIETY (UK)
December 2013 - May 2014
Global quantification of the yeast proteome
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
May 2013 - December 2014
Application of advanced MS instrumentation to protein ligand binding and PTM characterisation
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
January 2015 - January 2016
Mass spectrometry imaging for biology and biotechnology
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
January 2014 - December 2014
GlycoBioM
UNIVERSITY OF MANCHESTER (UK)
August 2014 - February 2015
DNA damage induced phosphorylation and regulation of NF-kappaB
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
April 2014 - September 2017
ProteoFormer – a software toolkit for top-down proteomics
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
July 2014 - November 2015