Dr Stephen Young BSc PhD FHEA

Image of Dr Stephen Young

Institute of Inflammation and Ageing
Reader in Experimental Rheumatology

Contact details

Address
Rheumatology Research Group
Institute of Inflammation and Ageing (IIA)
University of Birmingham
Queen Elizabeth Hospital
Birmingham
B15 2WB

Dr Young's research centers on the complex processes that give rise to chronic inflammatory diseases in humans. In particular, he takes a molecular and cellular approach to understanding the factors which give rise to aberrations in signalling pathways that underlie the immune pathology associated with diseases such as rheumatoid arthritis, lupus, vasculitis and uveitis.

Methodological approaches include analysis of signalling pathways at the level of the single cell, molecular interaction analysis using surface plasmon resonance and metabolite profiling using NMR-based metabolomics. Recently his focus has been on the role of PTPN22 variants in altering immune cell function and how this gene responds to hypoxia and cigarette smoke.

Dr Young has also developed and applied methods for NMR-based metabolomic analysis of inflammatory diseases to segregate patients groups, predict outcome and predict responses to therapy. Urine metabolite profiles have been used to predict whether RA patents will respond to anti-TNF therapy and this approach is being applied to other cohorts and other therapies. Dr Young has been able to use serum metabolic profile from very early arthritis (within 3 months of symptom onset) to discriminate between those who have a self-limiting disease and those who develop a chronic arthritis.

Qualifications

  • Fellowship of the Higher Education Academy, 2007
  • PhD Biochemistry/Haematology, University College London, 1978
  • BSc (Hons) Applied Chemistry, The Hatfield Polytechnic, 1973

Biography

Stephen Young qualified with a BSc (Hons) in Applied Chemistry from the Hatfield Polytechnic in 1973. A year out in Industry with Beecham’s Pharmaceuticals enthused him for laboratory science and its potential, and he went on to study for a PhD in Haematology/Biochemistry at University College London. He then moved to the Albert Einstein College of Medicine in New York for 3 years to work in the Department of Biophysics and the Liver Research Centre. He returned to the UK to the Liver Centre at King’s College Hospital in London before joining the Department of Rheumatology in Birmingham in 1985 as a Lecturer. Stephen has continued to work in Birmingham studying the cellular and molecular basis of rheumatoid arthritis.

He has built on his background and an interest in chemistry to bring innovative new technologies to the College, in particular high-field NMR spectroscopy and surface plasmon resonance which he makes use of in his translational research into inflammatory human diseases with a particular focus on rheumatoid arthritis. He is a keen promoter of the need to provide good quality information about their condition to patients with chronic diseases and established the first comprehensive WWW service about arthritis.

Stephen has taken an active lead role in teaching at a number of levels. He developed and was lead on the MSc in Rheumatology and coordinated the MSc in Immunology for a number of years. He is a member of the Curriculum Committee for the University of Birmingham's highly-rated BMedSc course.

Current research focuses on the interactions between genes, environment and metabolism to alter immune function and drive chronic inflammation. These studies have the potential to provide novel approaches to diagnosis and prognosis in important conditions such as rheumatoid arthritis, ageing and trauma.

Teaching

Postgraduate supervision

Stephen is an experienced supervisor with 20 students successfully complete PhDs under his supervision. He is interested in supervising doctoral research students in the following areas:

  • Gene/environment interactions promoting chronic autoimmune inflammatory diseases
  • Metabolomics of Inflammation
  • Immune dysregulation in chronic inflammation and ageing

 If you are interesting in studying any of these subject areas please contact Stephen on the contact details above, or for any general doctoral research enquiries, please email: dr@contacts.bham.ac.uk or call +44 (0)121 414 5005.

For a full list of available Doctoral Research opportunities, please visit our Doctoral Research programme listings.

Research

RESEARCH THEMES

Metabolomics of inflammation; immune cell signalling dysregulation in chronic disease.

RESEARCH ACTIVITY

Stephen’s research centres on the complex processes that give rise to chronic inflammatory diseases in humans. In particular, he takes a molecular and cellular approach to understanding the factors which give rise to aberrations in signalling pathways that underlie the immune pathology associated with diseases such as rheumatoid arthritis, vasculitis and uveitis. He has been innovative in implementing and developing a number of novel technologies. These include analysis of signalling pathways at the level of the single cell, molecular interaction analysis using surface plasmon resonance and metabolite profiling using NMR-based metabolomics.

Signalling aberrations in inflammatory disease

Abnormal function of peripheral blood T lymphocytes is characteristic of rheumatoid arthritis (RA); diminished proliferation and secretion of cytokines following in vitro mitogen stimulation are observed.  Stephen was the first to demonstrate that a TCR-linked signalling abnormality underlies this and since then he has further characterised these pathways and shown that extrinsic factors can lead to signalling dysregulation. In particular TNF, acting through acid sphingomyelinase, suppresses plasma membrane calcium signals and oxidation leads to inactivation of protein tyrosine phosphatases (PTP). He has also found that this occurs in the healthy elderly, partially explaining the depressed signalling and function of lymphocytes in ageing.  This has led to investigations of the interactions between a variant PTP N22 gene known to associated with arrange of autoimmune disease and the extrinsic factors such as hypoxia, inflammatory mediators and cigarette smoking, as an exemplar for environmental/genetic interactions in driving autoimmune arthritis. We have also shown that neutrophils expressing the variant of the PTPN22 gene are hyperactive which may explain their important role in rheumatoid arthritis.

He has extended this work to studies on endothelial cells in an attempt to explain the increase in cardiovascular disease associated with rheumatoid arthritis. He has shown that the earliest stages of the atherosclerotic process, the induction of endothelial cell dysfunction, can be mediated by TNF-induced sphingomyelinase, which in turn can be regulated by oxidative stress.

Metabolomics

This dysfunction in lymphocyte and endothelial function may result from a complex interaction between factors including genes, lifestyle, nutrition and infection. Metabolomics is a powerful new approach to the analysis of the overall metabolic activity of an organism, which may allow generation of a composite picture resulting from these many factors. Stephen has established NMR-based Metabolomics to study human inflammatory disease and this has proven to be a powerful tool for stratifying patients with complex diseases such as Uveitis and Rheumatoid Arthritis, and neurological diseases. He is applying these methods to analysis of rheumatoid arthritis, Lupus and Behcet’s Disease in close collaboration with the RA-MAP, RACE, ARUK Microbiome and MASTERPLANS consortia.

Click on the link below to listen to a Rheumatology Podcast where Stephen Young discusses with Prof Rob Moots, Editor of Rheumatology, a paper on antibodies formed in patients against an import therapeutic drug infliximab.

Other activities

  • Associate Editor of the Rheumatology journal, official journal of the British Society for Rheumatology
  • External Examiner MSc Immunology King’s College London (2012-)
  • External Examiner BSc Medical Sciences University of Exeter (2012-)

Publications

Goh YS, Necchi F, O'Shaughnessy C, Miocoli F, Gavini M, Young SP, Msefula C, Gondwe E, Mandala W, Gordon M, Saul A and MacLennan CA (2016) Bactericidal Immunity to Salmonella in Africans and Mechanisms Causing its Failure in HIV Infection. PLOS Negl Trop Dis 10(4):e0004604

Jutley GS and Young SP (2015) Metabolomics to identify biomarkers and as a predictive tool in inflammatory diseases. Best Pract Res Clin Rheumatol 29(6):770-82

McGrath CM and Young SP (2015) Lipid and Metabolic Changes in Rheumatoid Arthritis. Curr Rheumatol Rep 17(9):57

Kapoor SR, McGrath CM, Fitzpatrick MA and Young SP (2015) Metabolomics in rheumatology. Rheumatology (Oxford) 54(12):2124-5

Hou TZ, Qureshi OS, Wang CJ, Baker J, Young SP, Walker LS and Sansom DM (2015) A transendocytosis model of CTLA-4 function predicts its suppressive behavior on regulatory T cells. J Immunol 194(5):2148-59

Bayley R, Kite KA, McGettrick HM, Smith JP, Kitas GD, Buckley CD and Young SP (2015) The autoimmune-associated genetic variant PTPN22 R620W enhances neutrophil activation and function in patients with rheumatoid arthritis and healthy individuals. Ann Rheum Dis 74(8):1588-95

Fitzpatrick MA, McGrath CM and Young SP (2014) Pathomx: An interactive workflow-based tool for the analysis of metabolomic data. BMC Bioinformatics 15:396

Young SP, Kapoor SR, Viant MR, Byrne JJ, Filer A, Buckley CD, Kitas GD and Raza K (2013) The impact of inflammation on metabolomic profiles in patients with arthritis. Arthritis & Rheumatism 65(8):2015-23

Rider DA, Bayley R, Clay E and Young SP (2013) Does oxidative inactivation of CD45 phosphatase in rheumatoid arthritis underlie immune hyporesponsiveness? Antioxidants & Redox Signaling 19(18):2280-5

Kapoor SR, Filer A, Fitzpatrick M, Fisher BA, Taylor PC, Buckley CD, McInnes IB, Raza K and Young SP (2013) Metabolic profiling predicts response to anti-tumor necrosis factor α therapy in patients with rheumatoid arthritis. Arthritis Rheum 65(6):1448-56