Gerry Melino

University of Rome Tor Vergata, Roma, Latium, Italy

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Publications (471)3047.97 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Metastasis is a multistep cell-biological process, which is orchestrated by many factors, including metastasis activators and suppressors. Metastasis Suppressor 1 (MTSS1) was originally identified as a metastasis suppressor protein whose expression is lost in metastatic bladder and prostate carcinomas. However, recent findings indicate that MTSS1 acts as oncogene and pro-migratory factor in melanoma tumors. Here, we identify and characterized a molecular mechanism controlling MTSS1 expression, which impinges on a pro-tumorigenic role of MTSS1 in breast tumors. We found that in normal and in cancer cell lines ΔNp63 is able to drive the expression of MTSS1 by binding to a p63-binding responsive element localized in the MTSS1 locus. We reported that ΔNp63 is able to drive the migration of breast tumor cells by inducing the expression of MTSS1. Notably, in three human breast tumors data sets the MTSS1/p63 co-expression is a negative prognostic factor on patient survival, suggesting that the MTSS1/p63 axis might be functionally important to regulate breast tumor progression.Oncogene advance online publication, 29 June 2015; doi:10.1038/onc.2015.230.
    Oncogene 06/2015; DOI:10.1038/onc.2015.230 · 8.56 Impact Factor
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    ABSTRACT: During physiological aerobic metabolism, the epidermis undergoes significant oxidative stress as a result of the production of reactive oxygen species (ROS). To maintain a balanced oxidative state, cells have developed protective antioxidant systems, and preliminary studies suggest that the transcriptional factor p63 is involved in cellular oxidative defence. Supporting this hypothesis, the ΔNp63α isoform of p63 is expressed at high levels in the proliferative basal layer of the epidermis. Here we identify the CYGB gene as a novel transcriptional target of ΔNp63 that is involved in maintaining epidermal oxidative defence. The CYGB gene encodes cytoglobin, a member of the globin protein family, which facilitates the diffusion of oxygen through tissues and acts as a scavenger for nitric oxide or other ROS. By performing promoter activity assays and chromatin immunoprecipitation, reverse transcriptase quantitative PCR and western blotting analyses, we confirm the direct regulation of CYGB by ΔNp63α. We also demonstrate that CYGB has a protective role in proliferating keratinocytes grown under normal conditions, as well as in cells treated with exogenous hydrogen peroxide. These results indicate that ΔNp63, through its target CYGB has an important role in the cellular antioxidant system and protects keratinocytes from oxidative stress-induced apoptosis. The ΔNp63-CYGB axis is also present in lung and breast cancer cell lines, indicating that CYGB-mediated ROS-scavenging activity may also have a role in epithelial tumours. In human lung cancer data sets, the p63-CYGB interaction significantly predicts reduction of patient survival.Oncogene advance online publication, 22 June 2015; doi:10.1038/onc.2015.222.
    Oncogene 06/2015; DOI:10.1038/onc.2015.222 · 8.56 Impact Factor
  • Ivano Amelio, Gerry Melino
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    ABSTRACT: HIFs have long been associated with resistance to therapy, metastasis, and poor survival rates in cancer patients. In parallel, although the tumor-suppressor p53 acts as the first barrier against tumor transformation, its inactivation also appears to be crucial for enabling cancer progression at advanced stages. p53 has been proposed to antagonize HIF, and emerging evidence suggests that the p53 siblings p63 and p73 also participate in this interplay. Crosstalk between HIFs and the p53 family acts as a determinant of cancer progression through regulating angiogenesis, the tumor microenvironment, dormancy, metastasis, and recurrence. We discuss the possible mechanisms underlying this regulation and the controversies in this field in an attempt to provide a unified view of current knowledge. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Trends in Biochemical Sciences 05/2015; DOI:10.1016/j.tibs.2015.04.007 · 13.52 Impact Factor
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    ABSTRACT: TAp73 is a tumour suppressor transcriptional factor, belonging to p53 family. Alteration of TAp73 in tumours might lead to reduced DNA damage response, cell cycle arrest and apoptosis. Carcinogen-induced TAp73−/− tumours display also increased angiogenesis, associated to hyperactivition of hypoxia inducible factor signaling. Here, we show that TAp73 suppresses BNIP3 expression, directly binding its gene promoter. BNIP3 is a hypoxia responsive protein, involved in a variety of cellular processes, such as autophagy, mitophagy, apoptosis and necrotic-like cell death. Therefore, through different cellular process altered expression of BNIP3 may differently contribute to cancer development and progression. We found a significant upregulation of BNIP3 in human lung cancer datasets, and we identified a direct association between BNIP3 expression and survival rate of lung cancer patients. Our data therefore provide a novel transcriptional target of TAp73, associated to its antagonistic role on HIF signaling in cancer, which might play a role in tumour suppression.
    Cell cycle (Georgetown, Tex.) 05/2015; DOI:10.1080/15384101.2015.1044178 · 5.01 Impact Factor
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    ABSTRACT: Targeting the ubiquitin-proteasome system (UPS) and ubiquitin-like signalling systems (UBL) has been considered a promising therapeutic strategy to treat cancer, neurodegenerative and immunological disorders. There have been multiple efforts recently to identify novel compounds that efficiently modulate the activities of different disease-specific components of the UPS-UBL. However, it is evident that polypharmacology (the ability to affect multiple independent protein targets) is a basic property of small molecules and even highly potent molecules would have a number of "off target" effects. Here we have explored publicly available high-throughput screening data covering a wide spectrum of currently accepted drug targets in order to understand polypharmacology of small molecules targeting different components of the UPS-UBL. We have demonstrated that molecules targeting a given UPS-UBL protein also have high odds to target a given off target spectrum. Moreover, the off target spectrum differs significantly between different components of UPS-UBL. This information can be utilized further in drug discovery efforts, to improve drug efficiency and to reduce the risk of potential side effects of the prospective drugs designed to target specific UPS-UBL components
    Oncotarget 04/2015; 6(12). · 6.63 Impact Factor
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    ABSTRACT: Platelets play an important role in cardiovascular thrombosis as well as in many other pathological conditions such as inflammation, atherosclerosis and cancer. While multi-target strategies to treat complex diseases are gaining considerable attention, current development of antiplatelet therapies is mostly oriented towards several single targets, arising from our present understanding of the regulation of platelet activation. Limited efforts to develop multi-target agents or multidrug therapies are mostly due to a lack of a systematic basis to define target combinations with synergistic effects. Here we discuss the perspective to use high content phenotypic screening of in vitro models as a potential source for inference of synergetic multi-target strategies to control platelet activation.
    Mini Reviews in Medicinal Chemistry 04/2015; 15(8):622-9. DOI:10.2174/1389557515666150219124018 · 3.19 Impact Factor
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    ABSTRACT: Epidermolytic ichthyosis (BCIE, OMIM 113800), is an autosomal dominant disorder of the skin caused by mutations in keratin genes KRT1 and KRT10. We present two sporadic patients showing a mild diffuse ichthyosis with palmoplantar keratoderma. Interestingly, one of them shows a significant hyperkeratosis of palms and soles similar to those present in the Meleda disease (OMIM 248300). In this paper we would clarify the genetic difference between the two patients, giving rise to the different phenotype. Clinical evaluation, followed by histological and molecular analysis has been established for these patients. We demonstrated the presence of a genetic cutaneous mosaicism. Both patients carry the KRT1 pI479T substitution, but in the palmoplantar areas of one of them, only the mutated allele is expressed (hemizygous). This leads to highlight a new type of cutaneous mosaic, the palmoplantar mosaicism. © 2015 European Academy of Dermatology and Venereology.
    Journal of the European Academy of Dermatology and Venereology 04/2015; DOI:10.1111/jdv.13153 · 3.11 Impact Factor
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    ABSTRACT: p53 family members, p63 and p73, play a role in controlling early stage of myogenic differentiation. We demonstrated that TAp63gamma, unlike the other p53 family members, is markedly up-regulated during myogenic differentiation in murine C2C7 cell line. We also found that myotubes formation was inhibited upon TAp63gamma knock-down, as also indicated by atrophyic myotubes and reduction of myoblasts fusion index. Analysis of TAp63gamma-dependend transcripts identified several target genes involved in skeletal muscle contractility energy metabolism, myogenesis and skeletal muscle autocrine signaling. These results indicate that TAp63gamma is a late marker of myogenic differentiation and, by controlling different sub-sets of target genes, it possibly contributes to muscle growth, remodeling, functional differentiation and tissue homeostasis.
    Cell cycle (Georgetown, Tex.) 03/2015; 14(6):894-901. DOI:10.4161/15384101.2014.988021 · 5.01 Impact Factor
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    ABSTRACT: Atherosclerosis is a chronic inflammatory disease characterized by the infiltration of pro-inflammatory macrophages into a lipid-laden plaque. ITCH is an E3 ubiquitin ligase that has been shown to polarize macrophages to an anti-inflammatory phenotype. We therefore investigated the effect of ITCH deficiency on the development of atherosclerosis. ApoE-/-ITCH-/- mice fed a western diet for 12 weeks showed increased circulating M2 macrophages together with a reduction in plaque formation. Bone marrow transplantation recreated the haemopoietic phenotype of increased circulating M2 macrophages but failed to affect plaque development. Intriguingly, the loss of ITCH lead to a reduction in circulating cholesterol levels through interference with nuclear SREBP2 clearance. This resulted in increased LDL reuptake through upregulation of LDL receptor expression. Furthermore, ApoE-/-ITCH-/- mice exhibit reduced hepatic steatosis, increased mitochondrial oxidative capacity and an increased reliance on fatty acids as energy source. We found that ITCH ubiquitinates SIRT6, leading to its breakdown, and thus promoting hepatic lipid infiltration through reduced fatty acid oxidation. The E3 Ubiquitin Ligase ITCH modulates lipid metabolism impacting on atherosclerosis progression independently from effects on myeloid cells polarization through control of SIRT6 and SREBP2 ubiquitination. Thus, modulation of ITCH may provide a target for the treatment of hypercholesterolemia and hyperlipidemia.
    Scientific Reports 03/2015; 5:9023. DOI:10.1038/srep09023 · 5.58 Impact Factor
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    ABSTRACT: The predominant p63 isoform, ΔNp63, is a master regulator of normal epithelial stem cell (SC) maintenance. However, in vivo evidence of the regulation of cancer stem cell (CSC) properties by p63 is still limited. Here, we exploit the transgenic MMTV-ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2) mouse model of carcinogenesis to dissect the role of p63 in the regulation of mammary CSC self-renewal and breast tumorigenesis. ErbB2 tumor cells enriched for SC-like properties display increased levels of ΔNp63 expression compared with normal mammary progenitors. Down-regulation of p63 in ErbB2 mammospheres markedly restricts self-renewal and expansion of CSCs, and this action is fully independent of p53. Furthermore, transplantation of ErbB2 progenitors expressing shRNAs against p63 into the mammary fat pads of syngeneic mice delays tumor growth in vivo. p63 knockdown in ErbB2 progenitors diminishes the expression of genes encoding components of the Sonic Hedgehog (Hh) signaling pathway, a driver of mammary SC self-renewal. Remarkably, p63 regulates the expression of Sonic Hedgehog (Shh), GLI family zinc finger 2 (Gli2), and Patched1 (Ptch1) genes by directly binding to their gene regulatory regions, and eventually contributes to pathway activation. Collectively, these studies highlight the importance of p63 in maintaining the self-renewal potential of mammary CSCs via a positive modulation of the Hh signaling pathway.
    Proceedings of the National Academy of Sciences 03/2015; 112(11). DOI:10.1073/pnas.1500762112 · 9.81 Impact Factor
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    ABSTRACT: Recently, AMP-activated protein kinase (AMPK) has emerged as a key regulator of energy balance at cellular and whole-body levels. Due to the involvement in multiple signaling pathways, AMPK efficiently controls ATP-consuming/ATP-generating processes to maintain energy homeostasis under stress conditions. Loss of the kinase activity or attenuation of its expression leads to a variety of metabolic disorders and increases cancer risk. In this review, we discuss recent findings on the structure of AMPK, its activation mechanisms, as well as the consequences of its targets in regulation of metabolism. Particular attention is given to low-molecular-weight compounds that activate or inhibit AMPK; the perspective of therapeutic use of such modulators in treatment of several common diseases is discussed.
    Biochemistry (Moscow) 02/2015; 80(2):127-144. DOI:10.1134/S0006297915020017 · 1.35 Impact Factor
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    ABSTRACT: Tumor hypoxia and hypoxia-inducible factor 1 (HIF-1) activation are associated with cancer progression. Here, we demonstrate that the transcription factor TAp73 opposes HIF-1 activity through a nontranscriptional mechanism, thus affecting tumor angiogenesis. TAp73-deficient mice have an increased incidence of spontaneous and chemically induced tumors that also display enhanced vascu- larization. Mechanistically, TAp73 interacts with the regulatory sub- unit (α) of HIF-1 and recruits mouse double minute 2 homolog into the protein complex, thus promoting HIF-1α polyubiquitination and consequent proteasomal degradation in an oxygen-independent manner. In human lung cancer datasets, TAp73 strongly predicts good patient prognosis, and its expression is associated with low HIF-1 activation and angiogenesis. Our findings, supported by in vivo and clinical evidence, demonstrate a mechanism for oxygen- independent HIF-1 regulation, which has important implications for individualizing therapies in patients with cancer.
    Proceedings of the National Academy of Sciences 12/2014; DOI:10.1073/pnas.1410609111 · 9.81 Impact Factor
  • European journal of dermatology: EJD 12/2014; DOI:10.1684/ejd.2014.2446 · 1.95 Impact Factor
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    ABSTRACT: Serine and glycine are amino acids that provide the essential precursors for the synthesis of proteins, nucleic acids and lipids. Employing 3 subsequent enzymes, phosphoglycerate dehydrogenase (PHGDH), phosphoserine phosphatase (PSPH), phosphoserine aminotransferase 1 (PSAT1), 3-phosphoglycerate from glycolysis can be converted in serine, which in turn can by converted in glycine by serine methyl transferase (SHMT). Besides proving precursors for macromolecules, serine/glycine biosynthesis is also required for the maintenance of cellular redox state. Therefore, this metabolic pathway has a pivotal role in proliferating cells, including cancer cells. In the last few years an emerging literature provides genetic and functional evidences that hyperactivation of serine/glycine biosynthetic pathway drives tumorigenesis. Here, we extend these observations performing a bioinformatics analysis using public cancer datasets. Our analysis highlighted the relevance of PHGDH and SHMT2 expression as prognostic factor for breast cancer, revealing a substantial ability of these enzymes to predict patient survival outcome. However analyzing patient datasets of lung cancer our analysis reveled that some other enzymes of the pathways, rather than PHGDH, might be associated to prognosis. Although these observations require further investigations they might suggest a selective requirement of some enzymes in specific cancer types, recommending more cautions in the development of novel translational opportunities and biomarker identification of human cancers.
    Oncotarget 11/2014; 5(22). · 6.63 Impact Factor
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    ABSTRACT: Metabolic adaptation has emerged as a hallmark of cancer and a promising therapeutic target, as rapidly proliferating cancer cells adapt their metabolism increasing nutrient uptake and reorganizing metabolic fluxes to support biosynthesis. The transcription factor p73 belongs to the p53-family and regulates tumorigenesis via its two N-terminal isoforms, with (TAp73) or without (ΔNp73) a transactivation domain. TAp73 acts as tumor suppressor, at least partially through induction of cell cycle arrest and apoptosis and through regulation of genomic stability. Here, we sought to investigate whether TAp73 also affects metabolic profiling of cancer cells. Using high throughput metabolomics, we unveil a thorough and unexpected role for TAp73 in promoting Warburg effect and cellular metabolism. TAp73-expressing cells show increased rate of glycolysis, higher amino acid uptake and increased levels and biosynthesis of acetyl-CoA. Moreover, we report an extensive TAp73-mediated upregulation of several anabolic pathways including polyamine and synthesis of membrane phospholipids. TAp73 expression also increases cellular methyl-donor S-adenosylmethionine (SAM), possibly influencing methylation and epigenetics, and promotes arginine metabolism, suggestive of a role in extracellular matrix (ECM) modeling. In summary, our data indicate that TAp73 regulates multiple metabolic pathways that impinge on numerous cellular functions, but that, overall, converge to sustain cell growth and proliferation.
    Oncotarget 11/2014; 5(24). · 6.63 Impact Factor
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    ABSTRACT: Both in epithelial development as well as in epithelial cancers, the p53 family member p63 plays a crucial role acting as a master transcriptional regulator. P63 steady state protein levels are regulated by the E3 ubiquitin ligase Itch, via a physical interaction between the PPxY consensus sequence (PY motif) of p63 and one of the 4 WW domains of Itch; this substrate recognition process leads to protein-ubiquitylation and p63 proteasomal degradation. The interaction of the WW domains, a highly compact protein-protein binding module, with the short proline-rich sequences is therefore a crucial regulatory event that may offer innovative potential therapeutic opportunity. Previous molecular studies on the Itch-p63 recognition have been performed in vitro using the Itch-WW2 domain and the peptide interacting fragment of p63 (pep63), which includes the PY motif. Itch-WW2-pep63 interaction is also stabilized in vitro by the conformational constriction of the S-S cyclization in the p63 peptide. The PY motif of p63, as also for other proteins, is characterized by the nearby presence of a (T/S)P motif, which is a potential recognition site of the WW domain of the IV group present in the prolyl-isomerase Pin1. In this study, we demonstrate, by in silico and spectroscopical studies using both the linear pep63 and its cyclic form, that the threonine phosphorylation of the (T/S)PPPxY motif may represent a crucial regulatory event of the Itch-mediated p63 ubiquitylation, increasing the Itch-WW domains-p63 recognition event and stabilizing in vivo the Itch-WW-p63 complex. Moreover, our studies confirm that the subsequently trans/cis proline isomerization of (T/S)P motif by the Pin1 prolyl-isomerase, could modulate the E3-ligase interaction, and that the (T/S)pPtransPPxY motif represent the best conformer for the ItchWW-(T/S)PPPxY motif recognition.
    Cell cycle (Georgetown, Tex.) 11/2014; 13(20):3207-3217. DOI:10.4161/15384101.2014.951285 · 5.01 Impact Factor
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    ABSTRACT: TAp73, a member of the p53 family, has been traditionally considered a tumor suppressor gene, but a recent report has claimed that it can promote cellular proliferation. This assumption is based on biochemical evidence of activation of anabolic metabolism, with enhanced pentose phosphate shunt (PPP) and nucleotide biosynthesis. Here, while we confirm that TAp73 expression enhances anabolism, we also substantiate its role in inhibiting proliferation and promoting cell death. Hence, we would like to propose an alternative interpretation of the accumulating data linking p73 to cellular metabolism: we suggest that TAp73 promotes anabolism to counteract cellular senescence rather than to support proliferation.
    Aging 11/2014; 6(11):921-30. · 4.89 Impact Factor
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    ABSTRACT: The epidermis is a multilayered stratified epithelium, continuously regenerated by differentiating keratinocytes, that requires the transcription factor p63 for its development and maintenance. The TP63 gene encodes two major protein isoforms, TAp63 and ΔNp63, which have both transactivating and transcriptional repressing activities and regulate a wide range of target genes. TAp63 shows clear pro-apoptotic activity, mediated both by death receptors (CD95, TNF, TRAIL) and mitochondrial (bax, puma) pathways. Conversely, ΔNp63 protects from apoptosis by directly competing for TAp63 target promoters or sequestering it, forming inactive tetramers. Accordingly, p63 is expressed in epithelial tumours, contributing to both tumorigenesis and chemoresistance. However, the predominant physiological role of p63 is in epithelial development, as demonstrated by the lack of epidermis and other epithelia in p63-deficient mice. The specific role of TAp63 and ΔNp63 isoforms in epithelial development remains mostly unclear. Nevertheless, recent work utilizing in vivo genetic complementation of TAp63 and/or ΔNp63 into a p63 null background has shed new light into the specific functions of the two isoforms and allowed the in vivo validation of several p63 transcriptional targets, originally identified by microarray analysis in in vitro systems. However, despite concerted efforts to address the role of p63 isoforms, several questions remain unanswered. The main aim of this review is to critically discuss the data available in the literature and thoroughly analyze the models proposed.
    Cell cycle (Georgetown, Tex.) 10/2014; 6(3):274-284. DOI:10.4161/cc.6.3.3797 · 5.01 Impact Factor
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    ABSTRACT: Isatin (1H-indole-2,3-dione) is an endogenous natural compound under intense development in medicinal chemistry. Here, we characterize isatin Schiff base derivative by X-ray crystallography. We describe a derivative that crystallizes E-isomer form in the triclinic space group P (1) over bar; a = 5.9580 (4) angstrom, b = 8.4184 (7) angstrom, c = 14.1801 (14) angstrom, alpha = 73.962 (8 degrees), beta = 83.184 (7)degrees, gamma = 81.143 (6)degrees. NMR data show that E-conformer interconverts to the Z-conformer when dissolved, this equilibrium weakly depends on the solvent type. The Z-isomer geometry and the energetics of Delta EE-Z interconversion barriers were determined by quantum chemical calculations. The isomers are further characterized by means of FT-IR and UV Vis spectroscopy.
    Journal of Molecular Structure 10/2014; 1075:450-455. DOI:10.1016/j.molstruc.2014.07.008 · 1.60 Impact Factor
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    ABSTRACT: Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as /`accidental cell death/' (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. /`Regulated cell death/' (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects i
    Cell death and differentiation 09/2014; DOI:10.1038/cdd.2014.137 · 8.39 Impact Factor

Publication Stats

20k Citations
3,047.97 Total Impact Points

Institutions

  • 1988–2015
    • University of Rome Tor Vergata
      • • Dipartimento di Medicina dei Sistemi
      • • Dipartimento di Scinze e Tecnologie Chimiche
      • • Dipartimento di Biologia
      Roma, Latium, Italy
  • 2013–2014
    • Saint-Petersburg State Institute of Technology
      Sankt-Peterburg, St.-Petersburg, Russia
    • Cineca
      Casalecchio di Reno, Emilia-Romagna, Italy
    • University Health Network
      • Campbell Family Institute for Breast Cancer Research
      Toronto, Ontario, Canada
  • 2006–2013
    • Istituto Dermopatico dell'Immacolata
      Roma, Latium, Italy
  • 2003–2013
    • University of Leicester
      • Medical Research Council Toxicology Unit
      Leiscester, England, United Kingdom
    • Imperial College London
      Londinium, England, United Kingdom
  • 2012
    • University of Michigan
      • Life Sciences Institute
      Ann Arbor, MI, United States
    • Vlaams Instituut voor Biotechnologie
      • Inflammation Research Center (IRC)
      Gand, Flemish, Belgium
  • 2011
    • European Brain Research Institute
      Roma, Latium, Italy
  • 2009–2011
    • Foundation Santa Lucia
      Roma, Latium, Italy
    • Hungarian Academy of Sciences
      Budapeŝto, Budapest, Hungary
  • 1997–2010
    • The American University of Rome
      Roma, Latium, Italy
  • 2008
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 2007
    • Harvard Medical School
      • Department of Cell Biology
      Boston, MA, United States
  • 2004
    • Medical Research Council (UK)
      Londinium, England, United Kingdom
  • 2002
    • Ospedale Pediatrico Bambino Gesù
      Roma, Latium, Italy
  • 1997–2002
    • Newcastle University
      • Northern Institute for Cancer Research
      Newcastle upon Tyne, ENG, United Kingdom
  • 2001
    • Sungkyunkwan University
      • Department of Dermatology
      Sŏul, Seoul, South Korea
    • Institut de Cancérologie Gustave Roussy
      Île-de-France, France
  • 1998–2001
    • Sapienza University of Rome
      Roma, Latium, Italy
  • 1999
    • Universität Konstanz
      • Molecular Toxicology
      Constance, Baden-Württemberg, Germany
  • 1996–1997
    • Università degli Studi dell'Aquila
      • Department of Biology
      Aquila, Abruzzo, Italy
  • 1995
    • Mediterranean University of Reggio Calabria
      Reggio di Calabria, Calabria, Italy
  • 1993
    • Universidade Federal do Ceará
      • Departamento de Fisiologia e Farmacologia
      Fortaleza, Estado do Ceara, Brazil