University of Liverpool (Institute of Translational Medicine)
Short Name: UoL
The University of Liverpool (UoL) was founded in 1881, is a member of the Russell Group of 24 leading research-led Universities in the UK and currently has ~30,000 enrolled students and 4,700 staff. The work for this project will primarily take place in the Wolfson Centre for Personalised Medicine and the cross-cutting MRC Centre for Drug Safety Science, both within the Department of Molecular and Clinical Pharmacology. The Department of Molecular and Clinical Pharmacology consists of 34 academics (including 12 full professors), and about 170 total staff. It is one of the largest Departments of Pharmacology in the UK. The multidisciplinary research teams of the department cover 5 key research areas: personalised medicine, drug safety science, infection pharmacology, neuropharmacology, and antimicrobial pharmacodynamics and therapeutics.
The University of Liverpool partners in this project have extensive experience in pharmacogenomics, adverse drug reactions, bioinformatics, personalised medicine, and the spectrum of genetic technologies from candidate gene approaches through genome-wide association and exome- sequencing studies to whole genome sequencing. They are currently involved in pre-emptive pharmacogenomic genotyping of both primary and secondary care patients in Liverpool, and Prof Sir Pirmohamed is involved at a national level in the selection and prioritisation of pharmacogenomic variants as a prerequisite to a national pharmacogenomics service.
The Wolfson Centre for Personalised Medicine (WCPM) houses a multidisciplinary team of personalized medicine researchers engaged in collaborative research with partners across the globe. The primary focus of the WCPM is the identification of predictive biomarkers of drug safety and efficacy with the aim of translation from ‘bench-to-bedside’. The WCPM itself comprises a 1000 square metres of space containing state-of- the- art equipment for the purposes of nucleic acid extraction, storage, governance and analysis. This includes an automated robotic archive (SmaRTStore) integrated with a laboratory information system (StarLIMS) with a capacity and ability to retrieve on demand, up to 250,000 DNA samples. The WCPM also houses a Sequenom MALDI- TOF and TaqMan 7900HT Real Time PCR systems for genetic analysis. Sited within the WCPM is also bioinformatics clusters that will be necessary for storage of any genetic data accumulated. The bioinf1 cluster comprises eight identical compute nodes and an additional large memory compute node geared towards fragment assembly problems. A number of bioinformatics programs have been installed and are accessible across all nodes. The eight compute nodes each comprise two Intel Xeon(R) quad-core CPUs with 36GB memory, whilst the large memory node is an HP Proliant DL 380 G6 server with 128GB memory. Studies utilizing these technologies are undertaken with the ultimate aim of developing easy access for patients to truly personalized medicine. In addition to translation into clinical practice, the WCPM puts significant emphasis into education of clinicians and scientists alike, as well as public engagement activities to promote personalized medicine (Pharmacogenomics 2013;14:861-7).
The MRC Centre for Drug Safety Science is the only Centre of its kind in the UK which evaluates the mechanisms of adverse drug reactions. It contains a suite of mass spectrometers which are used for bioanalysis of drugs and metabolites, and proteomics. The Centre focuses on drug safety issues with a view to understanding mechanisms, which then allow for prevention through prediction and safe drug design. The Centre has also recently been awarded £5million for state-of-the-art equipment including single cell genomics, 700MHz NMR platform, mass cytometer, and high-end mass spectrometers for bioanalysis, proteomics and lipidomics.
The Centre for Genomic Research (UoL-CGR) at the University of Liverpool is a facility that has well-established processes to provide users access to genomic technology and expertise. It has been functioning productively and sustainably for more than 10 years. Each year we support around 150 users and 350 projects. The laboratory currently runs multiple next generation sequencing machines (Illumina NovaSeq, HiSeq and MiSeq platforms as well as Pacific Biosciences RS II and Sequel platforms), supported by automated laboratory workflows and investment in high performance computing (HPC) capability. The CGR is involved in diverse projects that encompass de novo genome and re-sequencing projects as well as expression profiling of pathogens, mammalian systems and plants. In most cases, the CGR is involved in all stages of experimental design, sample processing and analyses. Data quality is assessed using automated pipelines and bioinformatic analysis, if required, can be provided by our informatics team, based on a series of pipelines for RNAseq, variant calling, phylogeny construction, microbiome analysis, genome assembly and others.
Other European projects:
- The Ubiquitous Pharmacogenomics (U-PGx, ) consortium is a pan-European EU Horizon 2020-funded initiative, which is undertaking a large prospective international multicenter study to implement pre-emptive pharmacogenetic testing to determine its impact on clinical outcomes and cost-effectiveness compared to standard of
- EU Pharmacogenetics of Anticoagulant Therapy (EU-PACT) which was designed to test the role of pharmacogenetics in determining the effectiveness of vitamin K antagonists and showed the utility of genotype guided dosing of warfarin over standard care (see reference 3 above)
- Prediction-ADR is an EU-FP7 programme evaluating the genetic factors responsible for predisposing to statin myopathy and ACE inhibitor induced
- WEB-RADR – an IMI consortium evaluating the role of electronic media in identifying signals of adverse drug reactions
Role in the project:
Given our extensive expertise in pharmacogenomics and personalised medicine, we will be able to contribute widely to the programme. Specifically, we will be the leading team for the evaluation committee regarding technical activities on “sequencing” that will follow all phases of the PCP project. In addition, we will contribute to e-medication aspects of the project where we have extensive expertise in the reporting formats, the evidence needed for implementation of testing, and interpretation and prescribing advice to clinicians
Prof Sir Munir Pirmohamed
Prof Sir Munir Pirmohamed (male) is Director of the MRC Centre for Drug Safety Sciences and the Wolfson Centre for Personalised Medicine in Liverpool. He holds the David Weatherall Chair of Medicine and is the only NHS Chair of Pharmacogenetics in the UK. Professor Pirmohamed is a Fellow of the UK Academy of Medical Sciences, and an inaugural NIHR Senior Investigator. He has published over 500 articles, and has an H-index of 97 (Google Scholar). He is a Member of the Commission on Human Medicines and Chair of its Pharmacovigilance Expert Advisory Group, and is a Non-Executive Director for NHS England. His group’s work encompasses research within the wider field of personalised medicine and pharmacogenomics, with a particular interest in adverse drug reactions.
Dr Richard Turner
Dr Richard Turner (male) is a Clinical Lecturer in Clinical Pharmacology & Therapeutics, and holds an inaugural Health Education England Genomics Research and Innovation Fellowship. His research interests focus on the pharmacogenomics of cardiovascular disease, and the impact of rare variation on drug response using the UK 100,000 Genomes Project.
Professor Christiane Hertz-Fowler
Professor Christiane Hertz-Fowler (female) holds a Personal Chair in Pathogen Genomics and has research interests in understanding the genomic signatures that underlie human host susceptibility and disease progressions. Having helped set up and develop the Centre for Genomic Research, she currently focuses on developing and maintaining database/data-mining infrastructure, combined with expertise in curation and annotation. She is currently Head and Dean of the Institute of Integrated Biology at the University of Liverpool.
In addition to this, a team of 70 people who work in the Wolfson Centre for Personalised Medicine will be able to provide day-to-day support for the project.
Main publications and awards:
Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, Farrar K, Park BK, Breckenridge AM. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18,820 patients. BMJ. 2004; 329:15-9.
McCormack M, Alfirevic A, Bourgeois S, Farrell JJ, Kasperaviciute D, Carrington M, Sills GJ, Marson T, Jia X, De Bakker PI, Chinthapalli K, Molokhia M, Johnson MR, O’Connor GD, Chaila E, Alhusaini S, Shianna KV, Radtke RA, Heinzen EL, Walley N, Pandolfo M, Pichler W, Park BK, Depondt C, Sisodiya SM, Goldstein DB, Deloukas P, Delanty N, Cavalleri GL, Pirmohamed M. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med. 2011; 364:1134-43.
Pirmohamed M, Burnside G, Eriksson N, Jorgensen AL, Toh CH, Nicholson T, Kesteven P, Christersson C, Whalstrom B, Stafberg C, Zhang JE, Leathart JB, Kohnke H, Maitland-Van Der Zee AH, Williamson PR, Daly AK, Avery P, Kamali F, Wadelius M. A Randomized Trial of Genotype-Guided Dosing of Warfarin. New England Journal of Medicine. 2013; 369:2294- 303.
Carr DF, Chaponda M, Jorgensen AL, Castro EC, Van Oosterhout JJ, Khoo SH, Lalloo DG, Heyderman RS, Alfirevic A, Pirmohamed M. Association of Human Leukocyte Antigen Alleles and Nevirapine Hypersensitivity in a Malawian HIV-Infected Population. Clin Infect Dis. 2013; 56:1330-1339.
Turner R M, & Pirmohamed M. Cardiovascular pharmacogenomics: expectations and practical benefits. Clin Pharmacol Ther. 2014; 95:281-293.
Turner R M, Park B K, Pirmohamed M. Parsing interindividual drug variability: an emerging role for systems pharmacology. Wiley Interdiscip Rev Syst Biol Med. 2015; 7: 221- 41.
Van Der Wouden C H, Cambon-Thomsen A, Cecchin E, Cheung K C, Davila-Fajardo C L, Deneer V H, Dolzan V, Ingelman-Sundberg M, Jonsson S, Karlsson M O, Kriek M, Mitropoulou C, Patrinos G P, Pirmohamed M, Samwald M, Schaeffeler E, Schwab M, Steinberger D, Stingl J, Sunder-Plassmann G, Toffoli G, Turner R M, Van Rhenen M H, Swen J J & Guchelaar H J 2017. Implementing Pharmacogenomics in Europe: Design and Implementation Strategy of the Ubiquitous Pharmacogenomics Consortium. Clin Pharmacol Ther. 2017; 101:341-358.
Hawcutt D B, Francis B, Carr D F, Jorgensen A L, Yin P, Wallin N, O’hara N, Zhang E J, Bloch K M, Ganguli A, Thompson B, Mcevoy L, Peak M, Crawford A A, Walker B R, Blair J C, Couriel J, Smyth R L & Pirmohamed M. Susceptibility to corticosteroid-induced adrenal suppression: a genome-wide association study. Lancet Respir Med, 2018; 6:442-450.
- The Department of Molecular and Clinical Pharmacology (University of Liverpool) was awarded The Queen’s Anniversary Award for Higher and Further Education (2018)
- Turner R M. GlaxoSmithKline Clinical Oral Communication Prize for oral research communications at the British Pharmacological Society Annual International Meeting (2015)