Research
Cell Signaling and proteostasis
* Our interests cover aspects of membrane trafficking (endocytosis, autophagy, mitochondrial dynamics) and cell signaling with a view to understanding mechanisms that lead to pathologies such as cancer and neurodegeneration (Parkinsons Disease). We use a broad array of traditional molecular cell biology approaches, but also "big data" approaches such as proteomics and next generation sequencing. One particular focus is on the ESCRT-0 complex which is critical for lysosomal sorting of receptors but also co-ordinates a number of signalling events.
* We are interested in ubiquitin biology with a specific focus on deubiquitylating enzymes (DUBs). Our laboratory provided the first example of specificity to a particular type of ubiquitin chain linkage (Lys63, AMSH) and has provided detailed characterisation of two endosomal DUBs, which control down-regulation of receptor tyrosine kinases (RTKs). Currently we have projects to identify other DUBs germane to cancer and neurodegeneration, which may represent attractive drug targets. We contribute to a drug discovery programme in this area together with other academic centres and industry partners.
* We have a particular interest in the RTK, Met, which is the receptor for hepatocyte growth/scatter factor. This receptor plays a key role in normal development but disregulation can lead to cancer and metastasis. Our main contribution in this area has been to define the Met degradation pathway and characterise the dependence upon proteasome activity.
* Our proteomics efforts are being applied to understand acquired drug resistance in cancer and the contingencies associated with specific mutations of oncogenes such as KRAS as a component of an EU FP7 network COLTHERES.
Research grants
Exosome biogenesis: the role of sortilin in cancer development and progression
NORTH WEST CANCER RESEARCH INCORPORATING CLATTERBRIDGE CANCER RESEARCH (UK)
January 2016 - April 2019
The flipside to Parkin- regulation of mitochondrial deubiquitylase activity
PARKINSONS DISEASE SOCIETY OF THE UK (UK)
September 2016 - August 2019
Mitochondrial ubiquitin dynamics and apoptotic cell death
MEDICAL RESEARCH COUNCIL
May 2016 - May 2019
Towards the clinical positioning of a first selective DUB inhibitor
NORTH WEST CANCER RESEARCH INCORPORATING CLATTERBRIDGE CANCER RESEARCH (UK)
October 2018 - December 2021
European Research Training to Decipher The Ub Code : identification of potential biomarkers and drug targets (Ubicode)
EUROPEAN COMMISSION
January 2018 - December 2022
Fly models for Mitophagy
FORMA THERAPEUTICS (USA)
September 2016 - February 2017
Wellcome Trust Four-year PhD Studentship 2016
WELLCOME TRUST (UK)
October 2016 - April 2021
Protein Homeostasis and the Ubiquitination pathway in Parkinson's disease
CELGENE LTD (USA), FORMA THERAPEUTICS (USA)
March 2017 - June 2023
Beyond Parkin: An investigation into alternative modulators of Mitophagy in Parkinson’s disease.
PARKINSONS DISEASE SOCIETY OF THE UK (UK)
January 2020 - May 2023
Wellcome Trust Four Year Cellular and Molecular Physiology PhD Programme 2018
WELLCOME TRUST (UK)
October 2018 - March 2023
Wellcome Trust Four-Year PhD Studentship with the Cellular and Molecular Physiology PhD Programme
WELLCOME TRUST (UK)
October 2014 - September 2018
MELANOPARK
EUROPEAN COMMISSION
July 2015 - June 2017
Wellcome Trust Four Year PhD Studentship with the PhD Programme in Cellular and Molecular Physiology - 2010
WELLCOME TRUST (UK)
October 2010 - March 2015
The KRAS regulated kinase DCLK1: downstream elements and their roles in cancer
NORTH WEST CANCER RESEARCH INCORPORATING CLATTERBRIDGE CANCER RESEARCH (UK)
October 2014 - September 2017
Isogenic cell lines for targeted therapy discovery and development in BAP1-deficient mesothelioma
BRITISH LUNG FOUNDATION (UK)
October 2012 - January 2016
Characterisation of the dynamic ESCRT-0 interactome
NORTH WEST CANCER RESEARCH FUND
April 2012 - December 2014
CIC bioGUNE / University of Liverpool PhD programme for 2012/13
CIC BIOGUNE (SPAIN)
October 2012 - December 2016
Plasticity of epithelial cell boundaries governed by EGF and actin remodelling.
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
November 2014 - October 2017
Modelling and predicting resistance to molecular therapies in colorectal cancers
EUROPEAN COMMISSION
January 2011 - December 2014