Summary
I am currently a British Heart Foundation Intermediate Basic Science Fellow and Lecturer in Pulmonary Vascular Diseases in the Centre for Pharmacology and Therapeutics.
Our research involves integrated studies of -omics profiles in patients with pulmonary hypertension (PH). This includes working on whole genome sequencing data as part of the NIHR BioResource project, with pulmonary arterial hypertension (PAH) being one of the key rare diseases studied.
My work as a Junior Research Fellow at Imperial College focussed on the proteomic and metabolomic analysis of biofluids from patients with PH. Proteomic analyses have identified a multitude of proteins robustly associated with idiopathic pulmonary arterial hypertension (IPAH) in independent cohorts from 3 international expert PAH centres (Hammersmith, Sheffield and Paris). I have identified and validated a panel of 9 proteins that outperform established prognostic measures and have been awarded an Imperial Confidence in Concept grant to further study this panel, with a view to taking it to patent and pre-clinical development. The metabolomic analysis in collaboration with the Clinical Phenome Centre run by Prof. Jeremy Nicholson and external analyses by Metabolon Inc. have identified peaks and metabolites which can diagnose and prognosticate PH.
Previously, I worked as a Postdoctoral Research Fellow in the Rabinovitch Lab at Stanford University, California, USA. I worked on an NIH-funded U01 project which is investigating the utility of induced pluripotent stem cell (iPS)-derived endothelial cells (ECs) and genomic technologies in investigating the pathology of PAH. The genomic technologies being used include whole genome-, DNA methylation- and RNA-sequencing (RNAseq). I worked directly with the genetics laboratory of Prof. Michael Snyder in the analysis of RNAseq of control and patient ECs and the stem cell lab of Prof. Joseph Wu in the differentiation of endothelial cells from iPSCs. I took candidate genes and demonstrated their importance in PAH in terms of endothelial biology and effects in vivo in models of PAH.
I am a basic scientist by training (Natural Sciences: Pharmacology, First Class, Cambridge University) and started my studies into PH during my MRC PhD Studentship at Imperial College London, under the guidance of Prof. Martin Wilkins and Dr. John Wharton. During this time I studied iron homeostasis and biomarkers in pulmonary arterial hypertension (PAH). I found red cell distribution width (RDW), a measure of the variability in red blood cell size related to iron deficiency, outperformed other biomarkers in predicting survival in PAH patients. I also found elevated hepcidin levels in patients with PAH, which could be associated with the BMPR2 dysfunction typical in this disease, was related to iron deficiency. Iron deficiency in these patients was related to poorer survival. Following these findings the Wilkins Lab, in collaboration with the PH clinical services at Hammersmith Hospital, London, Papworth Hospital, Cambridge and The Royal Hallamshire Hospital, Sheffield, was awarded a 5-year BHF Programme Grant to study the importance of iron deficiency in PAH, including the performance of a placebo-controlled clinical trial investigating the utility of intravenous iron therapy in addition to standard therapies in 60 PAH patients.
Selected Publications
Journal Articles
Ulrich A, Wharton J, Thayer T, et al., 2020, Mendelian randomization analysis of red cell distribution width in pulmonary arterial hypertension, European Respiratory Journal, Vol:55, ISSN:0903-1936, Pages:1-9
Harbaum L, Ghataorhe P, Wharton J, et al., 2019, Reduced plasma levels of small HDL particles transporting fibrinolytic proteins in pulmonary arterial hypertension, Thorax, Vol:74, ISSN:1468-3296, Pages:380-389
Rhodes CJ, Batai K, Bleda M, et al., 2019, Genetic determinants of risk in pulmonary arterial hypertension: international case-control studies and meta-analysis, Lancet Respiratory Medicine, Vol:7, ISSN:2213-2600, Pages:227-238
Gräf S, Haimel M, Bleda M, et al., 2018, Identification of rare sequence variation underlying heritable pulmonary arterial hypertension, Nature Communications, Vol:9, ISSN:2041-1723, Pages:1-16
Rhodes CJ, Wharton J, Ghataorhe P, et al., 2017, Plasma proteome analysis in patients with pulmonary arterial hypertension: an observational cohort study, Lancet Respiratory Medicine, Vol:5, ISSN:2213-2600, Pages:717-726
Rhodes CJ, Ghataorhe P, Wharton J, et al., 2017, Plasma metabolomics implicate modified transfer RNAs and altered bioenergetics in the outcome of pulmonary arterial hypertension, Circulation, Vol:135, ISSN:0009-7322, Pages:460-475
Rhodes CJ, Im H, Cao A, et al., 2015, RNA Sequencing Analysis Detection of a Novel Pathway of Endothelial Dysfunction in Pulmonary Arterial Hypertension., American Journal of Respiratory and Critical Care Medicine, Vol:192, ISSN:1535-4970, Pages:356-366
Rhodes CJ, Wharton J, Boon RA, et al., 2013, Reduced microRNA-150 is associated with poor survival in pulmonary arterial hypertension., American Journal of Respiratory and Critical Care Medicine, Vol:187, Pages:294-302
Rhodes CJ, Howard LS, Busbridge M, et al., 2011, Iron Deficiency and Raised Hepcidin in Idiopathic Pulmonary Arterial Hypertension Clinical Prevalence, Outcomes, and Mechanistic Insights, Journal of the American College of Cardiology, Vol:58, ISSN:0735-1097, Pages:300-309
Rhodes CJ, Wharton J, Howard LS, et al., 2011, Red cell distribution width outperforms other potential circulating biomarkers in predicting survival in idiopathic pulmonary arterial hypertension, Heart, Vol:97, ISSN:1355-6037, Pages:1054-1060