Maria Monti

Professor of Biochemistry

Name Maria
Surname Monti
Institution University of Naples – Federico II
E-Mail montimar@unina.it
Address UniNa: Department of Chemical Sciences, Via Cinthia, Complesso Monte Sant’Angelo 21, 80126 Naples, Italy. Ceinge: CEINGE Biotecnologie Avanzate, Via G. Salvatore 486, 80126 Naples, Italy
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Maria Monti

Member PUBLICATIONS

  • Neutrophil Extracellular Traps as an Adhesion Substrate for Different Tumor Cells Expressing RGD-Binding Integrins.

    Publication Date: 09/08/2018 on International journal of molecular sciences
    by Monti M, De Rosa V, Iommelli F, Carriero MV, Terlizzi C, Camerlingo R, Belli S, Fonti R, Di Minno G, Del Vecchio S
    DOI: 10.3390/ijms19082350

    Neutrophil extracellular traps (NETs), in addition to their function as a host defense mechanism, play a relevant role in thrombus formation and metastatic dissemination of cancer cells. Here we screened different cancer cell lines endogenously expressing a variety of integrins for their ability to bind to NETs. To this end, we used NETs isolated from neutrophil-like cells as a substrate for adhesion assays of HT1080, U-87 MG, H1975, DU 145, PC-3 and A-431 cells. Levels of α5, αIIb, αv, β1, β3 and β5 chains were determined by western blot analysis in all cell lines and levels of whole integrins on the plasma membrane were assessed by fluorescence-activated cell sorting (FACS) analysis. We found that high levels of α5β1, αvβ3 and αvβ5 enhance cell adhesion to NETs, whereas low expression of α5β1 prevents cell attachment to NETs. Excess of cyclic RGD peptide inhibited cell adhesion to NETs by competing with fibronectin within NETs. The maximal reduction of such adhesion was similar to that obtained by DNase 1 treatment causing DNA degradation. Our findings indicate that NETs from neutrophil-like cells may be used as a substrate for large screening of the adhesion properties of cancer cells expressing a variety of RGD-binding integrins.

  • New insights on the functional role of URG7 in the cellular response to ER stress.

    Publication Date: 28/04/2018 on Biology of the cell
    by Armentano MF, Caterino M, Miglionico R, Ostuni A, Pace MC, Cozzolino F, Monti M, Milella L, Carmosino M, Pucci P, Bisaccia F
    DOI: 10.1111/boc.201800004

    Up-regulated Gene clone 7 (URG7) is an ER resident protein, whose expression is upregulated in the presence of hepatitis B virus X antigen (HBxAg) during HBV infection. In virus-infected hepatocytes, URG7 shows an anti-apoptotic activity due to the PI3K/AKT signaling activation, does not seem to have tumorigenic properties, but it appears to promote the development and progression of fibrosis. However, the molecular mechanisms underlying URG7 activity remain largely unknown.

  • Effects of iron on the aggregation propensity of the N-terminal fibrillogenic polypeptide of human apolipoprotein A-I.

    Publication Date: 05/04/2018 on Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine
    by Del Giudice R, Pesce A, Cozzolino F, Monti M, Relini A, Piccoli R, Arciello A, Monti DM
    DOI: 10.1007/s10534-018-0101-y

    Specific mutations in APOA1 gene lead to systemic, hereditary amyloidoses. In ApoA-I related amyloidosis involving the heart, amyloid deposits are mainly constituted by the 93-residue N-terminal region of the protein, here indicated as [1-93]ApoA-I. Oxidative stress is known to be an enhancing factor for protein aggregation. In healthy conditions, humans are able to counteract the formation and the effects of oxidative molecules. However, aging and atmospheric pollution increase the concentration of oxidative agents, such as metal ions. As the main effect of iron deregulation is proposed to be an increase in oxidative stress, we analysed the effects of iron on [1-93]ApoA-I aggregation. By using different biochemical approaches, we demonstrated that Fe(II) is able to reduce the formation of [1-93]ApoA-I fibrillar species, probably by stabilizing its monomeric form, whereas Fe(III) shows a positive effect on polypeptide fibrillogenesis. We hypothesize that, in healthy conditions, Fe(III) is reduced by the organism to Fe(II), thus inhibiting amyloid formation, whereas during ageing such protective mechanisms decline, thus exposing the organism to higher oxidative stress levels, which are also related to an increase in Fe(III). This alteration could contribute to the pathogenesis of amyloidosis.

  • Inositol trisphosphate receptor type 3-mediated enhancement of EGFR and MET co-targeting efficacy in non-small cell lung cancer detected by 18F-fluorothymidine.

    Publication Date: 04/04/2018 on Clinical cancer research : an official journal of the American Association for Cancer Research
    by Iommelli F, De Rosa V, Terlizzi C, Monti M, Panico M, Fonti R, Del Vecchio S
    DOI: 10.1158/1078-0432.CCR-17-3657

    Our aim was to test whether imaging with F-fluorothymidine (F-FLT) PET/CT was able to detect the combined effects of EGFR and MET inhibitors in oncogene-driven non-small lung cancer (NSCLC) and to elucidate the mechanisms underlying the enhanced efficacy of drug combination.

  • S-glutathionylation exerts opposing roles in the regulation of STAT1 and STAT3 signaling in reactive microglia.

    Publication Date: 01/03/2018 on Free radical biology & medicine
    by Butturini E, Cozzolino F, Boriero D, Carcereri de Prati A, Monti M, Rossin M, Canetti D, Cellini B, Pucci P, Mariotto S
    DOI: 10.1016/j.freeradbiomed.2018.02.005

    STAT1 and STAT3 are two transcription factors involved in a lot of cellular functions such as immune response, proliferation, apoptosis, and cell survival. A number of literature evidences described a yin-yang relationship between activation of STAT1 and STAT3 in neurodegenerative disorders where STAT1 exerts a pro-apoptotic effect whereas STAT3 shows neuroprotective properties through the inhibition of apoptosis. Although the role of oxidative-stress in the pathogenesis of neurodegeneration is clearly described, its influence in the regulation of these pathways is poorly understood. Herein, we demonstrate that HO rapidly induces phosphorylation of STAT1 whereas it is not able to influence phosphorylation of STAT3 in mouse microglia BV2 cells. The analysis of the molecular mechanism of STATs signaling reveals that HO induces S-glutathionylation of both STAT1 and STAT3. The same post-translational event exerts an opposing role in the regulation of STAT1 and STAT3 signaling. These data not only confirm redox sensibility of STAT3 signaling but also reveal for the first time that STAT1 is susceptible to redox regulation. A deep study of the molecular mechanism of STAT1 redox regulation, identifies Cys324 and Cys492 as the main targets of S-glutathionylation and confirms that S-glutathionylation does not impair JAK2 mediated STAT1 tyrosine phosphorylation. These results demonstrate that both phosphorylation and glutathionylation contribute to activation of STAT1 during oxidative stress and underline that the same post-translation event exerts an opposing role in the regulation of STAT1 and STAT3 signaling in microglia cells.

  • Incidence of DAA failure and the clinical impact of retreatment in real-life patients treated in the advanced stage of liver disease: Interim evaluations from the PITER network.

    Publication Date: 04/10/2017 on PloS one
    by Kondili LA, Gaeta GB, Brunetto MR, Di Leo A, Iannone A, Santantonio TA, Giammario A, Raimondo G, Filomia R, Coppola C, Amoruso DC, Blanc P, Del Pin B, Chemello L, Cavalletto L, Morisco F, Donnarumma L, Rumi MG, Gasbarrini A, Siciliano M, Massari M, Corsini R, Coco B, Madonia S, Cannizzaro M, Zignego AL, Monti M, Russo FP, Zanetto A, Persico M, Masarone M, Villa E, Bernabucci V, Taliani G, Biliotti E, Chessa L, Pasetto MC, Andreone P, Margotti M, Brancaccio G, Ieluzzi D, Borgia G, Zappulo E, Calvaruso V, Petta S, Falzano L, Quaranta MG, Weimer LE, Rosato S, Vella S, Giannini EG
    DOI: 10.1371/journal.pone.0185728

    Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure.

  • Inhibition of p110δ PI3K prevents inflammatory response and restenosis after artery injury.

    Publication Date: 27/09/2017 on Bioscience reports
    by Bilancio A, Rinaldi B, Oliviero MA, Donniacuo M, Monti MG, Boscaino A, Marino I, Friedman L, Rossi F, Vanhaesebroeck B, Migliaccio A
    DOI: 10.1042/BSR20171112

    Inflammatory cells play key roles in restenosis upon vascular surgical procedures such as bypass grafts, angioplasty and stent deployment but the molecular mechanisms by which these cells affect restenosis remain unclear. The p110δ isoform of phosphoinositide 3-kinase (PI3K) is mainly expressed in white blood cells. Here, we have investigated whether p110δ PI3K is involved in the pathogenesis of restenosis in a mouse model of carotid injury, which mimics the damage following arterial grafts. We used mice in which p110δ kinase activity has been disabled by a knockin (KI) point mutation in its ATP-binding site (p110δ(D910A/D910A) PI3K mice). Wild-type (WT) and p110δ(D910A/D910A) mice were subjected to longitudinal carotid injury. At 14 and 30 days after carotid injury, mice with inactive p110δ showed strongly decreased infiltration of inflammatory cells (including T lymphocytes and macrophages) and vascular smooth muscle cells (VSMCs), compared with WT mice. Likewise, PI-3065, a p110δ-selective PI3K inhibitor, almost completely prevented restenosis after artery injury. Our data showed that p110δ PI3K plays a main role in promoting neointimal thickening and inflammatory processes during vascular stenosis, with its inhibition providing significant reduction in restenosis following carotid injury. p110δ-selective inhibitors, recently approved for the treatment of human B-cell malignancies, therefore, present a new therapeutic opportunity to prevent the restenosis upon artery injury.

  • Toward the Standardization of Mitochondrial Proteomics: The Italian Mitochondrial Human Proteome Project Initiative.

    Publication Date: 13/09/2017 on Journal of proteome research
    by Alberio T, Pieroni L, Ronci M, Banfi C, Bongarzone I, Bottoni P, Brioschi M, Caterino M, Chinello C, Cormio A, Cozzolino F, Cunsolo V, Fontana S, Garavaglia B, Giusti L, Greco V, Lucacchini A, Maffioli E, Magni F, Monteleone F, Monti M, Monti V, Musicco C, Petrosillo G, Porcelli V, Saletti R, Scatena R, Soggiu A, Tedeschi G, Zilocchi M, Roncada P, Urbani A, Fasano M
    DOI: 10.1021/acs.jproteome.7b00350

    The Mitochondrial Human Proteome Project aims at understanding the function of the mitochondrial proteome and its crosstalk with the proteome of other organelles. Being able to choose a suitable and validated enrichment protocol of functional mitochondria, based on the specific needs of the downstream proteomics analysis, would greatly help the researchers in the field. Mitochondrial fractions from ten model cell lines were prepared using three enrichment protocols and analyzed on seven different LC-MS/MS platforms. All data were processed using neXtProt as reference database. The data are available for the Human Proteome Project purposes through the ProteomeXchange Consortium with the identifier PXD007053. The processed data sets were analyzed using a suite of R routines to perform a statistical analysis and to retrieve subcellular and submitochondrial localizations. Although the overall number of identified total and mitochondrial proteins was not significantly dependent on the enrichment protocol, specific line to line differences were observed. Moreover, the protein lists were mapped to a network representing the functional mitochondrial proteome, encompassing mitochondrial proteins and their first interactors. More than 80% of the identified proteins resulted in nodes of this network but with a different ability in coisolating mitochondria-associated structures for each enrichment protocol/cell line pair.

  • Structural determinants in ApoA-I amyloidogenic variants explain improved cholesterol metabolism despite low HDL levels.

    Publication Date: 05/09/2017 on Biochimica et biophysica acta
    by Del Giudice R, Domingo-Espín J, Iacobucci I, Nilsson O, Monti M, Monti DM, Lagerstedt JO
    DOI: 10.1016/j.bbadis.2017.09.001

    Twenty Apolipoprotein A-I (ApoA-I) variants are responsible for a systemic hereditary amyloidosis in which protein fibrils can accumulate in different organs, leading to their failure. Several ApoA-I amyloidogenic mutations are also associated with hypoalphalipoproteinemia, low ApoA-I and high-density lipoprotein (HDL)-cholesterol plasma levels; however, subjects affected by ApoA-I-related amyloidosis do not show a higher risk of cardiovascular diseases (CVD). The structural features, the lipid binding properties and the functionality of four ApoA-I amyloidogenic variants were therefore inspected in order to clarify the paradox observed in the clinical phenotype of the affected subjects. Our results show that ApoA-I amyloidogenic variants are characterized by a different oligomerization pattern and that the position of the mutation in the ApoA-I sequence affects the molecular structure of the formed HDL particles. Although lipidation increases ApoA-I proteins stability, all the amyloidogenic variants analyzed show a lower affinity for lipids, both in vitro and in ex vivo mouse serum. Interestingly, the lower efficiency at forming HDL particles is compensated by a higher efficiency at catalysing cholesterol efflux from macrophages. The decreased affinity of ApoA-I amyloidogenic variants for lipids, together with the increased efficiency in the cholesterol efflux process, could explain why, despite the unfavourable lipid profile, patients affected by ApoA-I related amyloidosis do not show a higher CVD risk.

  • The centrosomal OFD1 protein interacts with the translation machinery and regulates the synthesis of specific targets.

    Publication Date: 27/04/2017 on Scientific reports
    by Iaconis D, Monti M, Renda M, van Koppen A, Tammaro R, Chiaravalli M, Cozzolino F, Pignata P, Crina C, Pucci P, Boletta A, Belcastro V, Giles RH, Maria Surace E, Gallo S, Pende M, Franco B
    DOI: 10.1038/s41598-017-01156-x

    Protein synthesis is traditionally associated with specific cytoplasmic compartments. We now show that OFD1, a centrosomal/basal body protein, interacts with components of the Preinitiation complex of translation (PIC) and of the eukaryotic Initiation Factor (eIF)4F complex and modulates the translation of specific mRNA targets in the kidney. We demonstrate that OFD1 cooperates with the mRNA binding protein Bicc1 to functionally control the protein synthesis machinery at the centrosome where also the PIC and eIF4F components were shown to localize in mammalian cells. Interestingly, Ofd1 and Bicc1 are both involved in renal cystogenesis and selected targets were shown to accumulate in two models of inherited renal cystic disease. Our results suggest a possible role for the centrosome as a specialized station to modulate translation for specific functions of the nearby ciliary structures and may provide functional clues for the understanding of renal cystic disease.