Imperial College London

DrEnricoPetretto

Faculty of MedicineInstitute of Clinical Sciences

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3313 1468enrico.petretto Website

 
 
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Location

 

231ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

105 results found

Moreno-Moral A, Bagnati M, Koturan S, Ko J-H, Fonseca C, Harmston N, Game L, Martin J, Ong V, Abraham DJ, Denton CP, Behmoaras J, Petretto Eet al., 2018, Changes in macrophage transcriptome associate with systemic sclerosis and mediate GSDMA contribution to disease risk, ANNALS OF THE RHEUMATIC DISEASES, Vol: 77, Pages: 596-601, ISSN: 0003-4967

JOURNAL ARTICLE

Olona A, Terra X, Ko J-H, Grau-Bové C, Pinent M, Ardevol A, Diaz AG, Moreno-Moral A, Edin M, Bishop-Bailey D, Zeldin DC, Aitman TJ, Petretto E, Blay M, Behmoaras Jet al., 2018, Epoxygenase inactivation exacerbates diet and aging-associated metabolic dysfunction resulting from impaired adipogenesis., Mol Metab, Vol: 11, Pages: 18-32

OBJECTIVE: When molecular drivers of healthy adipogenesis are perturbed, this can cause hepatic steatosis. The role of arachidonic acid (AA) and its downstream enzymatic cascades, such as cyclooxygenase, in adipogenesis is well established. The exact contribution of the P450 epoxygenase pathway, however, remains to be established. Enzymes belonging to this pathway are mainly encoded by the CYP2J locus which shows extensive allelic expansion in mice. Here we aimed to establish the role of endogenous epoxygenase during adipogenesis under homeostatic and metabolic stress conditions. METHODS: We took advantage of the simpler genetic architecture of the Cyp2j locus in the rat and used a Cyp2j4 (orthologue of human CYP2J2) knockout rat in two models of metabolic dysfunction: physiological aging and cafeteria diet (CAF). The phenotyping of Cyp2j4-/- rats under CAF was integrated with proteomics (LC-MS/MS) and lipidomics (LC-MS) analyses in the liver and the adipose tissue. RESULTS: We report that Cyp2j4 deletion causes adipocyte dysfunction under metabolic challenges. This is characterized by (i) down-regulation of white adipose tissue (WAT) PPARγ and C/EBPα, (ii) adipocyte hypertrophy, (iii) extracellular matrix remodeling, and (iv) alternative usage of AA pathway. Specifically, in Cyp2j4-/- rats treated with a cafeteria diet, the dysfunctional adipogenesis is accompanied by exacerbated weight gain, hepatic lipid accumulation, and dysregulated gluconeogenesis. CONCLUSION: These results suggest that AA epoxygenases are essential regulators of healthy adipogenesis. Our results uncover their synergistic role in fine-tuning AA pathway in obesity-mediated hepatic steatosis.

JOURNAL ARTICLE

Pereira M, Petretto E, Gordon S, Bassett JHD, Williams GR, Behmoaras Jet al., 2018, Common signalling pathways in macrophage and osteoclast multinucleation., J Cell Sci, Vol: 131

Macrophage cell fusion and multinucleation are fundamental processes in the formation of multinucleated giant cells (MGCs) in chronic inflammatory disease and osteoclasts in the regulation of bone mass. However, this basic cell phenomenon is poorly understood despite its pathophysiological relevance. Granulomas containing multinucleated giant cells are seen in a wide variety of complex inflammatory disorders, as well as in infectious diseases. Dysregulation of osteoclastic bone resorption underlies the pathogenesis of osteoporosis and malignant osteolytic bone disease. Recent reports have shown that the formation of multinucleated giant cells and osteoclast fusion display a common molecular signature, suggesting shared genetic determinants. In this Review, we describe the background of cell-cell fusion and the similar origin of macrophages and osteoclasts. We specifically focus on the common pathways involved in osteoclast and MGC fusion. We also highlight potential approaches that could help to unravel the core mechanisms underlying bone and granulomatous disorders in humans.

JOURNAL ARTICLE

Rodriguez-Martinez A, Posma JM, Ayala R, Neves AL, Anwar M, Petretto E, Emanueli C, Gauguier D, Nicholson JK, Dumas M-Eet al., 2018, MWASTools: an R/bioconductor package for metabolome-wide association studies, BIOINFORMATICS, Vol: 34, Pages: 890-892, ISSN: 1367-4803

JOURNAL ARTICLE

Sigmundsson K, Ojala JRM, Öhman MK, Österholm A-M, Moreno-Moral A, Domogatskaya A, Chong LY, Sun Y, Chai X, Steele JAM, George B, Patarroyo M, Nilsson A-S, Rodin S, Ghosh S, Stevens MM, Petretto E, Tryggvason Ket al., 2018, Culturing functional pancreatic islets on α5-laminins and curative transplantation to diabetic mice., Matrix Biol

The efficacy of islet transplantation for diabetes treatment suffers from lack of cadaver-derived islets, islet necrosis and long transfer times prior to transplantation. Here, we developed a method for culturing mouse and human islets in vitro on α5-laminins, which are natural components of islet basement membranes. Adhering islets spread to form layers of 1-3 cells in thickness and remained normoxic and functional for at least 7 days in culture. In contrast, spherical islets kept in suspension developed hypoxia and central necrosis within 16 h. Transplantation of 110-150 mouse islets cultured on α5-laminin-coated polydimethylsiloxane membranes for 3-7 days normalized blood glucose already within 3 days in mice with streptozotocin-induced diabetes. RNA-sequencing of isolated and cultured mouse islets provided further evidence for the adhesion and spreading achieved with α5-laminin. Our results suggest that use of such in vitro expanded islets may significantly enhance the efficacy of islet transplantation treatment for diabetes.

JOURNAL ARTICLE

Solimena M, Schulte AM, Marselli L, Ehehalt F, Richter D, Kleeberg M, Mziaut H, Knoch K-P, Parnis J, Bugliani M, Siddiq A, Joerns A, Burdet F, Liechti R, Suleiman M, Margerie D, Syed F, Distler M, Gruetzmann R, Petretto E, Moreno-Moral A, Wegbrod C, Soenmez A, Pfriem K, Friedrich A, Meinel J, Wollheim CB, Baretton GB, Scharfmann R, Nogoceke E, Bonifacio E, Sturm D, Meyer-Puttlitz B, Boggi U, Saeger H-D, Filipponi F, Lesche M, Meda P, Dahl A, Wigger L, Xenarios I, Falchi M, Thorens B, Weitz J, Bokvist K, Lenzen S, Rutter GA, Froguel P, von Buelow M, Ibberson M, Marchetti Pet al., 2018, Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes, DIABETOLOGIA, Vol: 61, Pages: 641-657, ISSN: 0012-186X

JOURNAL ARTICLE

Baliga NS, Bjoerkegren JLM, Boeke JD, Boutros M, Crawford NPS, Dudley AM, Farber CR, Jones A, Levey AI, Lusis AJ, Mak HC, Nadeau JH, Noyes MB, Petretto E, Seyfried NT, Steinmetz LM, Vonesch SCet al., 2017, The State of Systems Genetics in 2017 commentary, CELL SYSTEMS, Vol: 4, Pages: 7-15, ISSN: 2405-4712

JOURNAL ARTICLE

Beltrami C, Besnier M, Shantikumar S, Shearn AIU, Rajakaruna C, Laftah A, Sessa F, Spinetti G, Petretto E, Angelini GD, Emanueli Cet al., 2017, Human Pericardial Fluid Contains Exosomes Enriched with Cardiovascular-Expressed MicroRNAs and Promotes Therapeutic Angiogenesis, MOLECULAR THERAPY, Vol: 25, Pages: 679-693, ISSN: 1525-0016

JOURNAL ARTICLE

Chen T-D, Rotival M, Chiu L-Y, Bagnati M, Ko J-H, Srivastava PK, Petretto E, Pusey CD, Lai P-C, Aitman TJ, Cook HT, Behmoaras Jet al., 2017, Identification of Ceruloplasmin as a Gene that Affects Susceptibility to Glomerulonephritis Through Macrophage Function, GENETICS, Vol: 206, Pages: 1139-1151, ISSN: 0016-6731

JOURNAL ARTICLE

Coan PM, Hummel O, Diaz AG, Barrier M, Alfazema N, Norsworthy PJ, Pravenec M, Petretto E, Huebner N, Aitman TJet al., 2017, Genetic, physiological and comparative genomic studies of hypertension and insulin resistance in the spontaneously hypertensive rat, DISEASE MODELS & MECHANISMS, Vol: 10, Pages: 297-306, ISSN: 1754-8403

JOURNAL ARTICLE

Heinig M, Adriaens ME, Schafer S, van Deutekom HWM, Lodder EM, Ware JS, Schneider V, Felkin LE, Creemers EE, Meder B, Katus HA, Ruehle F, Stoll M, Cambien F, Villard E, Charron P, Varro A, Bishopric NH, George AL, dos Remedios C, Moreno-Moral A, Pesce F, Bauerfeind A, Rueschendorf F, Rintisch C, Petretto E, Barton PJ, Cook SA, Pinto YM, Bezzina CR, Hubner Net al., 2017, Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy, GENOME BIOLOGY, Vol: 18, ISSN: 1474-760X

JOURNAL ARTICLE

Imprialou M, Petretto E, Bottolo L, 2017, Expression QTLs Mapping and Analysis: A Bayesian Perspective., Pages: 189-215

The aim of expression Quantitative Trait Locus (eQTL) mapping is the identification of DNA sequence variants that explain variation in gene expression. Given the recent yield of trait-associated genetic variants identified by large-scale genome-wide association analyses (GWAS), eQTL mapping has become a useful tool to understand the functional context where these variants operate and eventually narrow down functional gene targets for disease. Despite its extensive application to complex (polygenic) traits and disease, the majority of eQTL studies still rely on univariate data modeling strategies, i.e., testing for association of all transcript-marker pairs. However these "one at-a-time" strategies are (1) unable to control the number of false-positives when an intricate Linkage Disequilibrium structure is present and (2) are often underpowered to detect the full spectrum of trans-acting regulatory effects. Here we present our viewpoint on the most recent advances on eQTL mapping approaches, with a focus on Bayesian methodology. We review the advantages of the Bayesian approach over frequentist methods and provide an empirical example of polygenic eQTL mapping to illustrate the different properties of frequentist and Bayesian methods. Finally, we discuss how multivariate eQTL mapping approaches have distinctive features with respect to detection of polygenic effects, accuracy, and interpretability of the results.

BOOK CHAPTER

Krishnan ML, Van Steenwinckel J, Schang A-L, Yan J, Arnadottir J, Le Charpentier T, Csaba Z, Dournaud P, Cipriani S, Auvynet C, Titomanlio L, Pansiot J, Ball G, Boardman JP, Walley AJ, Saxena A, Mirza G, Fleiss B, Edwards AD, Petretto E, Gressens Pet al., 2017, Integrative genomics of microglia implicates DLG4 (PSD95) in the white matter development of preterm infants, NATURE COMMUNICATIONS, Vol: 8, ISSN: 2041-1723

JOURNAL ARTICLE

McDermott-Roe C, Leleu M, Rowe GC, Palygin O, Bukowy JD, Kuo J, Rech M, Hermans-Beijnsberger S, Schaefer S, Adami E, Creemers EE, Heinig M, Schroen B, Arany Z, Petretto E, Geurts AMet al., 2017, Transcriptome-wide co-expression analysis identifies LRRC2 as a novel mediator of mitochondrial and cardiac function, PLOS ONE, Vol: 12, ISSN: 1932-6203

JOURNAL ARTICLE

Moreno-Moral A, Pesce F, Behmoaras J, Petretto Eet al., 2017, Systems Genetics as a Tool to Identify Master Genetic Regulators in Complex Disease., Pages: 337-362

Systems genetics stems from systems biology and similarly employs integrative modeling approaches to describe the perturbations and phenotypic effects observed in a complex system. However, in the case of systems genetics the main source of perturbation is naturally occurring genetic variation, which can be analyzed at the systems-level to explain the observed variation in phenotypic traits. In contrast with conventional single-variant association approaches, the success of systems genetics has been in the identification of gene networks and molecular pathways that underlie complex disease. In addition, systems genetics has proven useful in the discovery of master trans-acting genetic regulators of functional networks and pathways, which in many cases revealed unexpected gene targets for disease. Here we detail the central components of a fully integrated systems genetics approach to complex disease, starting from assessment of genetic and gene expression variation, linking DNA sequence variation to mRNA (expression QTL mapping), gene regulatory network analysis and mapping the genetic control of regulatory networks. By summarizing a few illustrative (and successful) examples, we highlight how different data-modeling strategies can be effectively integrated in a systems genetics study.

BOOK CHAPTER

Nefzger CM, Rossello FJ, Chen J, Liu X, Knaupp AS, Firas J, Paynter JM, Pflueger J, Buckberry S, Lim SM, Williams B, Alaei S, Faye-Chauhan K, Petretto E, Nilsson SK, Lister R, Ramialison M, Powell DR, Rackham OJL, Polo JMet al., 2017, Cell Type of Origin Dictates the Route to Pluripotency, CELL REPORTS, Vol: 21, Pages: 2649-2660, ISSN: 2211-1247

JOURNAL ARTICLE

Petretto E, 2017, Genetics of Neurodevelopmental Disorders: Connecting The Dots in The Brain, 18th International Congress of Developmental Biology, Publisher: ELSEVIER SCIENCE BV, Pages: S4-S4, ISSN: 0925-4773

CONFERENCE PAPER

Rackham OJL, Langley SR, Oates T, Vradi E, Harmston N, Srivastava PK, Behmoaras J, Dellaportas P, Bottolo L, Petretto Eet al., 2017, A Bayesian Approach for Analysis of Whole-Genome Bisulfite Sequencing Data Identifies Disease-Associated Changes in DNA Methylation, GENETICS, Vol: 205, Pages: 1443-1458, ISSN: 0016-6731

JOURNAL ARTICLE

Schafer S, Viswanathan S, Widjaja AA, Lim W-W, Moreno-Moral A, DeLaughter DM, Ng B, Patone G, Chow K, Khin E, Tan J, Chothani SP, Ye L, Rackham OJL, Ko NSJ, Sahib NE, Pua CJ, Zhen NTG, Xie C, Wang M, Maatz H, Lim S, Saar K, Blachut S, Petretto E, Schmidt S, Putoczki T, Guimaraes-Camboa N, Wakimoto H, van Heesch S, Sigmundsson K, Lim SL, Soon JL, Chao VTT, Chua YL, Tan TE, Evans SM, Loh YJ, Jamal MH, Ong KK, Chua KC, Ong B-H, Chakaramakkil MJ, Seidman JG, Seidman CE, Hubner N, Sin KYK, Cook SAet al., 2017, IL-11 is a crucial determinant of cardiovascular fibrosis, NATURE, Vol: 552, Pages: 110-+, ISSN: 0028-0836

JOURNAL ARTICLE

Srivastava PK, Bagnati M, Delahaye-Duriez A, Ko J-H, Rotival M, Langley SR, Shkura K, Mazzuferi M, Danis B, van Eyll J, Foerch P, Behmoaras J, Kaminski RM, Petretto E, Johnson MRet al., 2017, Genome-wide analysis of differential RNA editing in epilepsy, GENOME RESEARCH, Vol: 27, Pages: 440-450, ISSN: 1088-9051

JOURNAL ARTICLE

Srivastava PK, Roncon P, Lukasiuk K, Gorter JA, Aronica E, Pitkanen A, Petretto E, Johnson MR, Simonato Met al., 2017, Meta-Analysis of MicroRNAs Dysregulated in the Hippocampal Dentate Gyrus of Animal Models of Epilepsy, ENEURO, Vol: 4, ISSN: 2373-2822

JOURNAL ARTICLE

Suresh J, Harmston N, Lim KK, Kaur P, Jin HJ, Lusk JB, Petretto E, Tolwinski NSet al., 2017, An embryonic system to assess direct and indirect Wnt transcriptional targets, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322

JOURNAL ARTICLE

Delahaye-Duriez A, Srivastava P, Shkura K, Langley SR, Laaniste L, Moreno-Moral A, Danis B, Mazzuferi M, Foerch P, Gazina EV, Richards K, Petrou S, Kaminski RM, Petretto E, Johnson MRet al., 2016, Rare and common epilepsies converge on a shared gene regulatory network providing opportunities for novel antiepileptic drug discovery, GENOME BIOLOGY, Vol: 17, ISSN: 1474-760X

JOURNAL ARTICLE

Diaz-Montana JJ, Rackham OJL, Diaz-Diaz N, Petretto Eet al., 2016, Web-based Gene Pathogenicity Analysis (WGPA): a web platform to interpret gene pathogenicity from personal genome data, BIOINFORMATICS, Vol: 32, Pages: 635-637, ISSN: 1367-4803

JOURNAL ARTICLE

Johnson MR, Shkura K, Langley SR, Delahaye-Duriez A, Srivastava P, Hill WD, Rackham OJL, Davies G, Harris SE, Moreno-Moral A, Rotival M, Speed D, Petrovski S, Katz A, Hayward C, Porteous DJ, Smith BH, Padmanabhan S, Hocking LJ, Starr JM, Liewald DC, Visconti A, Falchi M, Bottolo L, Rossetti T, Danis B, Mazzuferi M, Foerch P, Grote A, Helmstaedter C, Becker AJ, Kaminski RM, Deary IJ, Petretto Eet al., 2016, Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease, NATURE NEUROSCIENCE, Vol: 19, Pages: 223-+, ISSN: 1097-6256

JOURNAL ARTICLE

Kamaraj US, Gough J, Polo JM, Petretto E, Rackham OJLet al., 2016, Computational methods for direct cell conversion, CELL CYCLE, Vol: 15, Pages: 3343-3354, ISSN: 1538-4101

JOURNAL ARTICLE

Lewin A, Saadi H, Peters JE, Moreno-Moral A, Lee JC, Smith KGC, Petretto E, Bottolo L, Richardson Set al., 2016, MT-HESS: an efficient Bayesian approach for simultaneous association detection in OMICS datasets, with application to eQTL mapping in multiple tissues, BIOINFORMATICS, Vol: 32, Pages: 523-532, ISSN: 1367-4803

JOURNAL ARTICLE

Madan B, Ke Z, Harmston N, Ho SY, Frois AO, Alam J, Jeyaraj DA, Pendharkar V, Ghosh K, Virshup IH, Manoharan V, Ong EHQ, Sangthongpitag K, Hill J, Petretto E, Keller TH, Lee MA, Matter A, Virshup DMet al., 2016, Wnt addiction of genetically defined cancers reversed by PORCN inhibition, ONCOGENE, Vol: 35, Pages: 2197-2207, ISSN: 0950-9232

JOURNAL ARTICLE

Martinez-Micaelo N, Gonzalez-Abuin N, Ardevol A, Pinent M, Petretto E, Behmoaras J, Blay Met al., 2016, Leptin signal transduction underlies the differential metabolic response of LEW and WKY rats to cafeteria diet, JOURNAL OF MOLECULAR ENDOCRINOLOGY, Vol: 56, Pages: 1-10, ISSN: 0952-5041

JOURNAL ARTICLE

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