Dr Tom Piers
Lecturer in Neuroscience, NIHR Exeter BRC Translational Fellow
T.Piers@exeter.ac.uk
RILD Building Room L3.21/ RILD Level 3
University of Exeter Medical School, RILD Building, RD&E Hospital Wonford, Barrack Road, Exeter, EX2 5DW, UK
Overview
Tom is a Lecturer in Neuroscience (E&R) and NIHR Exeter Biomedical Research Centre Translational Fellow within the Department of Clinical and Biomedical Sciences. He graduated with a degree in Pharmacology from Leeds University that encompassed a year in Industry with GlaxoSmithKline in Harlow. He then worked for GSK at the newly established Neurology Discovery Performance Unit in Singapore before undertaking a PhD in microglial signalling at UCL Institute of Neurology, London. After post-doctoral studies at the MRC Centre for Synaptic Plasticity at Bristol University and Chonnam National University Hospital in Republic of Korea, Tom returned to UCL Institute of Neurology to develop human models of microglia using induced pluripotent stem cell (iPSC) technology to study the functional consequences of genetic variants associated with Alzheimer’s disease risk. Tom then moved to The Living Systems Institute at Exeter University as a Research Fellow to establish iPSC models of cortical neurons for the study of early changes in synaptogenesis that occur in AD. Tom then joined the Department of Clinical and Biomedical Sciences as a Lecturer in Neuroscience and Translational Fellow in the newly established Exeter Biomedical Research Centre. His lab focusses on understanding and modelling microglial cell state transitions using complex culture models and on the development of novel therapeutics that target microglia for the treatment of Alzheimer’s disease.
Qualifications
- PhD Microglial signalling (UCL Institute of Neurology)
- BSc (Hons) Pharmacology (Indus) (University of Leeds)
Career
Senior Research Associate, Queen Square Institute of Neurology, UCL
iPSC models of myeloid cells to investigate the role of AD-associated risk variants – focus on mitochondrial dysfunction and senescence (2020-2021)
Research Associate, Queen Square Institute of Neurology, UCL (2017-2020)
Research Associate, Therapeutic Innovation Group, UCL
Developed iPSC models to investigate the newly identified risk variants expressed in myeloid cells – in partnership with pharma (2014-2017)
Research Associate, Translational Neuroscience Research Group, School of Clinical Sciences, University of Bristol (2011-2014)
Research Assistant, GlaxoSmithKline Neurology Centre of Excellence for Drug Discovery, Singapore (2007-2008)
Research group links
Research
Research interests
It is now apparent that cellular responses to the pathology of neurological disorders rely on complex interplay between brain region vulnerability, temporal dynamics of pathogenesis, and the regulation of cell states. Pioneering single cell analyses in complex systems has identified vast transcriptional heterogeneity within classically defined cell types and over the last decade human genetic studies have shed light on variation associated with risk in diseases such as late onset Alzheimer’s disease (LOAD). Identified LOAD-associated risk variants likely act preferentially or exclusively on microglia, the immune cells of the brain, and a highly responsive and plastic cell type, placing them front and centre in the pathogenesis of this disease.
Our research harnesses the power of human induced pluripotent stem cells (iPSCs) coupled with genetic risk to provide complex in vitro models of microglia and organoids that enable us to study the phenotypic consequences of defined risk. We use a multidisciplinary approach to identify novel targets and pathways that can be therapeutically targeted using strategies including drug repurposing that have the potential to provide rapid translation of findings to the clinic.
Research projects
- Effect of disease-associated risk variants on epigenetic regulation of microglial cell states
- Synaptogenesis in cerebral organoids
- Subcellular characterisation of isoform profiles in the local translatome
- Tool generation for synapse quantitation in neuronal cell models
- Wnt signalling in synaptogenesis
Publications
Journal articles
. Recently, we reported oligoadenylate synthetase 1 (OAS1) contributed to the risk of Alzheimer’s disease, by its enrichment in transcriptional networks expressed by microglia. However, the function of OAS1 within microglia was not known.
. Using genotyping from 1313 individuals with sporadic Alzheimer’s disease and 1234 control individuals, we confirm the OAS1 variant, rs1131454, is associated with increased risk for Alzheimer’s disease. The same OAS1 locus has been recently associated with severe coronavirus disease 2019 (COVID-19) outcomes, linking risk for both diseases. The single nucleotide polymorphisms rs1131454(A) and rs4766676(T) are associated with Alzheimer’s disease, and rs10735079(A) and rs6489867(T) are associated with severe COVID-19, where the risk alleles are linked with decreased OAS1 expression. Analysing single-cell RNA-sequencing data of myeloid cells from Alzheimer’s disease and COVID-19 patients, we identify co-expression networks containing interferon (IFN)-responsive genes, including OAS1, which are significantly upregulated with age and both diseases. In human induced pluripotent stem cell-derived microglia with lowered OAS1 expression, we show exaggerated production of TNF-α with IFN-γ stimulation, indicating OAS1 is required to limit the pro-inflammatory response of myeloid cells.
. Collectively, our data support a link between genetic risk for Alzheimer’s disease and susceptibility to critical illness with COVID-19 centred on OAS1, a finding with potential implications for future treatments of Alzheimer’s disease and COVID-19, and development of biomarkers to track disease progression.' onclick='modalCall(this);return false;'>Abstract.
