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Full NameProfessor Stephen Pennington
Department:School of Medicine
Organisation:University College Dublin
- genetics, genomics and molecular biology
- cell and developmental biology/regenerative medicine
- physiology and non-communicable disease
Postgrad Medical Specialties
- General Practice
- Public Health
- Clinical Trials
- Community Medicine
- Geriatric Medicine
- Health Informatics
We are engaged in the application of the latest developments in proteomics strategies to the elucidation of disease mechanisms and identification of disease markers to make significant advances in personalised medicine by identifying and developing protein biomarkers to support patient stratification.
We are currently active in two major disease areas:
i) prostate cancer (see: Tonry C et al. The Role of Proteomics in Biomarker Development for Improved Patient Diagnosis and Clinical Decision Making in Prostate Cancer. Diagnostics. 2016, 6: 27; Staunton L et al, Profiling the tumor microenvironment proteome in prostate cancer using laser capture microdissection coupled to LC-MS EuPA Open Proteomics. 2016, 10:19-23.; Tonry CL, et al. Discovery and Longitudinal Evaluation of Candidate Protein Biomarkers for Disease Recurrence in Prostate Cancer. J Proteome Res. 2015, 14:2769-83)
ii) inflammatory arthritis (see: McArdle et al. Developing Clinically Relevant Biomarkers in Inflammatory Arthritis: A Multi-Platform Approach for Serum Candidate Protein Discovery. Proteomics Clin Appl. 2015 doi: 10.1002/prca.201500046; Mc Ardle A et al.. Early biomarkers of joint damage in rheumatoid and psoriatic arthritis. Arthritis Res Ther. 2015, 17:141. Ademowo OS, et al. Discovery and confirmation of a protein biomarker panel with potential to predict response to biological therapy in psoriatic arthritis. Ann Rheum Dis. 2014 doi: 10.1136/annrheumdis-2014-205417.)
We are particularly interested in translating our lab-based research findings to clinical utility (see: Hernandez B, Pennington SR, Parnell AC. Bayesian methods for proteomic biomarker development. EuPA Open Proteomics. 2015, 9:54-64; Percy et al.. Clinical Translation of MS-based Quantitative Plasma Proteomics: Status, Challenges, Requirements, and Potential. Expert Rev Proteomics. doi: 10.1080/14789450.2016.1205950) and have recently founded a small company - Atturos - to support this endeavour (www.atturos.com).
1. In recent studies undertaken in collaboration with colleagues in the Dana Farber Cancer Centre, USA, we have used a combined proteomic and transcriptomics (RNAseq) strategy to identify changes in the tumour microenvironment in prostate cancer. This has involved sophisticated laser capture micro dissection or epithelial and stromal regions of tissue with distinct pathologies (Gleason grade 3 vs. 4). In this way we have identified proteins and pathways that may contribute to pathogenesis of early stage prostate cancer that may serve as targets for therapeutic intervention or markers to better support the prognostically significant difference between tumours of Gleason grade 3+4 (Group II) and 4+3 (Group III) (Manuscript submitted: Mol Cancer Research). In the proposed project we will use the information gathered so far to investigate the role of individual proteins and pathways in the functional attributes of prostate cancer cells (proliferation, migration and other 'metastatic' properties).
2. We (FitzGerald) have proposed that psoriatic arthritis patients clinical phenotype is dictated by one of several known genotypes and in this project we will seek to identify the potential molecular mechanisms of this linkage. In particular, we will investigate the role played by the Act1 adaptor protein and protein ubiquitinylation in IL17 mediated signalling. GWAS studies have shown that SNP variants in the Act1 gene contribute to psoriatic arthritis and the proposed studies will support the elucidation of the molecular mechanism(s) by which this adaptor protein for the IL17 receptor may contribute to the pathogenesis of psoriatic arthritis.