Researchers at UCD


Simone Marcone

Systems Biology Ireland

Tel: 00353 1 716 6318


My research career began in 2007 when I moved from Rome, where I completed my university study in pharmaceutical chemistry, to the laboratories of the Catholic University in Campobasso (Italy), a centre of excellence for research into cardiovascular diseases and cancer. Here I discovered a passion for science and began acquiring laboratory and research skills including mass spectrometry. My research work focused on the discovery of biomarkers of paclitaxel resistance in ovarian cancer by using proteomics, and mass spectrometry of small molecules such as polyphenols and their role in cardiovascular diseases. 
In 2009 I moved to the UCD Conway Institute to study for my PhD. The project was on exploring endogenous molecules involved in the resolution of inflammation. I developed a chemical proteomic approach that deepened my knowledge of mass spectrometry, as well as cell and molecular biology assays for the detection of antiinflammatory effects of prostaglandins and peptides. As part of the project, I worked on the ¿Food for Health Ireland¿ project on characterizing the anti-atherogenic properties of bioactive peptides. This provided me with experience in industry led projects and insight into project managing. 
In 2013 I started a postdoctoral fellowship with Prof Des Fitzgerald in UCD on human platelet pharmacoproteomics, focusing on novel approaches to study proteomic signatures in health and disease and the effects of drugs. 
In February 2017 I started working in Systems Biology Ireland where I joined the group of Prof Walter Kolch on the study of childhood cancer, deciphering the signalling and transcriptional networks that drive highly aggressive embryonal tumours by using -omics and systems biology approaches. 



Peer Reviewed Journals

Di Michele M, Marcone S, Cicchillitti L, Della Corte A, Ferlini C, Scambia G, Donati MB, Rotilio D. (2010) '11. Glycoproteomics of paclitaxel resistance in human epithelial ovarian cancer cell lines: towards the identification of putative biomarkers'. Journal of Proteomics, . [Details]
Rotilio D, Della Corte A, D'Imperio M, Coletta W, Marcone S, Silvestri C, Giordano L, Di Michele M, Donati MB. (2012) 'Proteomics: bases for protein complexity understanding'. Thrombosis Research, . [Details]
Marcone S, Belton O, Fitzgerald DJ. (2016) 'Milk-derived bioactive peptides and their health promoting effects: a potential role in atherosclerosis'. British Journal of Clinical Pharmacology, . [Details]
Marcone S, Evans P, Fitzgerald DJ. (2016) '15-Deoxy-Δ12,14-Prostaglandin J2 Modifies Components of the Proteasome and Inhibits Inflammatory Responses in Human Endothelial Cells'. Frontiers in Immunology, . [Details]
Marcone S, Dervin F;Fitzgerald DJ (2015) 'Proteomic signatures of antiplatelet drugs: new approaches to exploring drug effects'. Journal of Thrombosis and Haemostasis, 13 Suppl 1 :1-31. [DOI] [Details]
de Gaetano M, Alghamdi K, Marcone S, Belton O (2015) 'Conjugated linoleic acid induces an atheroprotective macrophage MΦ2 phenotype and limits foam cell formation'. Journal of Inflammation, 12 . [DOI] [Details]
Marcone S, Haughton K, Simpson PJ, Belton O, Fitzgerald DJ (2015) 'Milk-derived bioactive peptides inhibit human endothelial-monocyte interactions via PPAR-γ dependent regulation of NF-κB'. Journal of Inflammation, 12 (1). [DOI] [Details]
de Gaetano M, Dempsey E, Marcone S, James WG, Belton O (2013) 'Conjugated linoleic acid targets Beta2 integrin expression to suppress monocyte adhesion'. J IMMUNOL, 191 (8):4326-4336. [DOI] [Details]
Marcone S, Fitzgerald DJ (2013) 'Proteomic identification of the candidate target proteins of 15-deoxy-delta12,14-prostaglandin J2'. Proteomics, 13 (14):2135-2139. [DOI] [Details]
Hilliard M, Frohnert C;Spillner C;Marcone S;Nath A;Lampe T;Fitzgerald DJ;Kehlenbach RH (2010) 'The anti-inflammatory prostaglandin 15-deoxy-delta(12,14)-PGJ2 inhibits CRM1-dependent nuclear protein export'. Journal of Biological Chemistry, 285 (29):22202-22210. [DOI] [Details]


Research Interests


My current research project in Systems Biology Ireland (SBI) is on the study of the pathogenesis of childhood cancer, identifying prognostic markers and novel therapeutic targets in MYC/MYCN-driven neuroblastoma by using -omics and systems biology approaches. 

Neuroblastoma is the most common childhood cancer in infancy with a highly variable prognosis. Amplification of transcription factors, such as MYCN, or overexpression of receptors, like TrkB, confers a highly malignant phenotype.


Other projects:

Platelet Pharmacoproteomics:

Platelets are cellular fragments that circulate in blood and play a critical role in preventing bleeding and in disease, specifically stroke and heart attacks. Drugs that inhibit the function of platelets have become a mainstay in the treatment of arterial disease, specifically in preventing vascular thrombosis. Given the complexity of the biology involved in platelet activation, antiplatelet agents are frequently combined to maximize platelet inhibition. These include aspirin, which blocks thromboxane and P2Y12 receptor antagonists that block ADP, two potent platelet activators. More recently, a new class of drug targets the PAR-1 receptor for platelet activation by thrombin. Two issues make it difficult to use antiplatelet drugs. First, the pharmacological response is highly variable between individuals with many patients continuing to experience recurrent thrombotic events and/or bleeding. Secondly, current platelet assays poorly predict clinical response, and fail to discriminate between drugs or to detect the impact of combining drugs. Indeed, rational approaches to combining drugs are nonexistent. Therefore, I used a proteomics to explore individual variability in the response to drugs and the impact of combination therapy. Proteomic profiling (large-scale study of proteins) provides an integrated and unbiased read-out of factors that regulate responses to antiplatelet drugs (genetic, environment). Sensitive label free quantitative mass spectrometry will provide platelet pharmacoproteomic profiles of individuals and drug effects. My preliminary work on platelet releasate shows distinct individual signatures as well as signatures of drugs alone and in combinations. This proof of concept provided limited information on the pathways involved, a limitation that will be overcome by phosphoprotein analysis. The approach may help industry in designing new therapeutic approaches and in monitoring drug combinations in vivo, which is impossible at present. Moreover, this study may help better understand individual differences in drug response and lead to rational approaches of tailoring therapy to individual patients.


Inflammation and atherosclerosis:

Prostaglandins are generated by the cyclooxigenases and exert a broad range of physiological and pathophysiological effects. They include 15-deoxy-delta12,14-PGJ2 (15d-PGJ2), that is derived from PGD2. 15d-PGJ2 is known to play a role in the resolution of inflammation, however the mechanism is unclear. 15d-PGJ2 covalently modifies cellular proteins, via a reactive α,β-unsaturated carbonyl group in its cyclopentenone ring, which, in turn, alters protein function. A chemical-proteomics-approach was used to identify the proteins modified by 15d-PGJ2. Human endothelial cells (EC) were treated with biotinylated-15d-PGJ2, the modified proteins extracted by affinity-purification and analysed by nanoLC-mass spectrometry. The assay identified 358 modified proteins and bioinformatics pathway analysis showed the ubiquitin-proteasome-system to be disproportionally enriched with 13 proteins found in the 19S-regulatory particle of the proteasome, a protein complex involved in the degradation of cellular proteins and processing of inflammatory proteins. Furthermore, 15d-PGJ2 reduced proteasome catalytic activity in EC. As a consequence of the reduction in proteasome activity, the activation of the transcription factor NF-kB was suppressed. Furthermore, 15d-PGJ2 decreased mRNA expression and protein levels of NF-kB target genes such as adhesion molecules and chemokines. This reduction was accompanied by inhibition of monocyte adhesion to EC and by decreased monocyte migration. The findings supported the hypothesis that 15d-PGJ2 suppresses inflammation through covalent modification of the proteasome pathway, acting as a proteasome inhibitor and consequently suppressing NF-kB transcriptional activity. To address whether 15d-PGJ2 was generated in vivo, immunohistochemistry of human atherosclerotic plaques obtained during carotid endarterectomy was performed. 15d-PGJ2 was detected in human plaques and was higher in plaques obtained from symptomatic patients (presenting with recent transient ischaemic attack) compared with asymptomatic patients. I also showed that proteasome proteins extracted from these tissue samples were modified by 15d-PGJ2. Together, these findings showed that 15d-PGJ2 is formed in vivo, covalently modifies proteins and is biologically active.




Developing as a Teacher

Teaching experience: I supervised several undergrad students for their thesis preparation, and two PhD students. I am currently developing and delivering tutorials for the "Cardiovascular and Renal Disease" module in Pharmacology


Internal Collaborators

Dr Paul Evans, UCD Chemistry department 
Dr Orina Belton, UCD Conway Institute  

External Collaborators

Prof Maria Benedetta Donati. Head, Laboratory of Translational Medicine. IRCCS Istituto Neurologico Mediterraneo Neuromed. Pozzilli, Italy

Dr Martin Quinn. Cardiology Department, St Vincent's University Hospital, Dublin

Dr James McRedmond, Java Clinical Trial, Dublin, Ireland