Valerie is an Honorary Group Leader, currently based at the the University of Cardiff. She is working with Group Leaders in the Signalling Programme. Valerie’s research is focused on the study of bioactive lipids in circulating blood cells, particularly platelets. She uses mass spectrometry to identify and characterise new signalling mediators. Since 2007, her group identified large families of lipids made by platelets, neutrophils and monocytes, and demonstrated that these are involved in innate immunity, blood clotting, cardiovascular disease and infection. Translational studies have established a role for these lipids in human thrombotic disease.
She has developed new methods to quantify aminophospholipids at the platelet surface, for example molecular species of amino-phospholipids and oxidized phospholipids that comprise the pro-coagulant surface, which is essential for blot formation. She leads/led a programme grant from British Heart Foundation (renewed 2020), and was an ERC Advanced Grant holder (2014-2019). Since 2017, she has been co-lead of LIPID MAPS, a multi-site Biomedical Resource supporting databases, tools, nomenclature and curation of lipids, funded by Wellcome Trust (>66K users, with Edward Dennis and Shankar Subramaniam (UCSD), Simon Andrews and Andrea Lopez, Babraham, and Bill Griffiths, Swansea).
She was Co-Director of the Systems Immunity Research Institute, Cardiff University from 2016-2020. She is co-investigator on an EU Marie Curie ITN (ArthritisHeal, Leiden), an EU Cost Network (EpiLipidNET) and an MRC Partnership Grant (MAP/UK, Imperial), and an Associate Group Lead at UK Dementia Research Institute (UKDRI) at Cardiff University.
Targeted metabolite assays that measure tens or hundreds of pre-selected metabolites, typically using liquid chromatography-mass spectrometry, are increasingly being developed and applied to metabolic phenotyping studies. These are used both as standalone phenotyping methods and for the validation of putative metabolic biomarkers obtained from untargeted metabolomics studies. However, there are no widely accepted standards in the scientific community for ensuring reliability of the development and validation of targeted metabolite assays (referred to here as 'targeted metabolomics'). Most current practices attempt to adopt, with modifications, the strict guidance provided by drug regulatory authorities for analytical methods designed largely for measuring drugs and other xenobiotic analytes. Here, the regulatory guidance provided by the European Medicines Agency, US Food and Drug Administration and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use are summarized. In this Perspective, we have adapted these guidelines and propose a less onerous 'tiered' approach to evaluate the reliability of a wide range of metabolomics analyses, addressing the need for community-accepted, harmonized guidelines for tiers other than full validation. This 'fit-for-purpose' tiered approach comprises four levels-discovery, screening, qualification and validation-and is discussed in the context of a range of targeted and untargeted metabolomics assays. Issues arising with targeted multiplexed metabolomics assays, and how these might be addressed, are considered. Furthermore, guidance is provided to assist the community with selecting the appropriate degree of reliability for a series of well-defined applications of metabolomics.
Progress in mass spectrometry lipidomics has led to a rapid proliferation of studies across biology and biomedicine. These generate extremely large raw datasets requiring sophisticated solutions to support automated data processing. To address this, numerous software tools have been developed and tailored for specific tasks. However, for researchers, deciding which approach best suits their application relies on ad hoc testing, which is inefficient and time consuming. Here we first review the data processing pipeline, summarizing the scope of available tools. Next, to support researchers, LIPID MAPS provides an interactive online portal listing open-access tools with a graphical user interface. This guides users towards appropriate solutions within major areas in data processing, including (1) lipid-oriented databases, (2) mass spectrometry data repositories, (3) analysis of targeted lipidomics datasets, (4) lipid identification and (5) quantification from untargeted lipidomics datasets, (6) statistical analysis and visualization, and (7) data integration solutions. Detailed descriptions of functions and requirements are provided to guide customized data analysis workflows.
Alterations in cellular metabolism underpin macrophage activation, yet little is known regarding how key immunological molecules regulate metabolic programs in macrophages. Here we uncover a function for the antigen presenting molecule CD1d in the control of lipid metabolism. We show that CD1d-deficient macrophages exhibit a metabolic reprogramming, with a downregulation of lipid metabolic pathways and an increase in exogenous lipid import. This metabolic rewiring primes macrophages for enhanced responses to innate signals, as CD1d-KO cells show higher signalling and cytokine secretion upon Toll-like receptor stimulation. Mechanistically, CD1d modulates lipid import by controlling the internalization of the lipid transporter CD36, while blocking lipid uptake through CD36 restores metabolic and immune responses in macrophages. Thus, our data reveal CD1d as a key regulator of an inflammatory-metabolic circuit in macrophages, independent of its function in the control of T cell responses.