References of "Mazzucchelli, Gabriel"
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See detailPotential Proteomic Biomarkers Associated To Mucosal Healing In Crohn’s Disease
MEUWIS, Marie-Alice ULg; Baiwir, Dominique ULg; Mazzucchelli, Gabriel ULg et al

Poster (2014, October 06)

Introduction and objectives: In Crohn's disease (CD), there is a discrepancy between clinical activity of the disease (symptoms) and intestinal healing. However absence of tissue healing is associated ... [more ▼]

Introduction and objectives: In Crohn's disease (CD), there is a discrepancy between clinical activity of the disease (symptoms) and intestinal healing. However absence of tissue healing is associated with the risk of relapse and tissue damage progression. Endoscopy is costly and invasive. Hence biomarkers correlating with intestinal healing could improve disease management. We aimed to identify potential biomarkers associated to CD mucosal healing by a shotgun proteomics label free study. Methods: We used the STORI clinical trial cohort (n=103) aiming at identifying markers associated to relapse prediction after Infliximab treatment withdrawals. We used serum samples of patients in clinical remission, grouped according to the degree of intestinal healing seen at endoscopy. We performed depletion of the 20 most abundant plasma proteins on each serum pools and ran a proteomics label free differential analysis using 2D-nanoUPLC-MSE HDMS Synapt G1 for data acquisition and Protein Lynks Global Server vs 2.4 for data analysis (Waters, Corp., Milford, USA). Results and Discussion: We obtained potential biomarkers and designed a multiplexed -selected reaction monitoring (SRM) method for validation of these candidates in each individual patient. The method may also be tested in an independent set of IBD patients with and without mucosal healing. Conclusions: This research strategy and results of SRM validation of potential biomarkers associated to mucosal healing in this cohort of CD patients as well as the tests done on other CD patients, may provide new opportunities for CD follow-up tests development. [less ▲]

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See detailAphid - symbiont interactions : multitrophic "omic" approaches to investigate multitrophic interactions
Bosquée, Emilie ULg; Bauwens, Julien ULg; Mazzucchelli, Gabriel ULg et al

Poster (2014, August)

« Omics » found recent developments due to significant improvement and availability of both separation and identification methods. For proteomics, functional information’s linked to the studied proteins ... [more ▼]

« Omics » found recent developments due to significant improvement and availability of both separation and identification methods. For proteomics, functional information’s linked to the studied proteins was brought when compared to genomic approach. For these reasons, a panel of tools is available to determine the proteome patterns related to differential adaptation of insects to cope with plant defence mechanisms or to transmit virus. The adaptation and metabolic changes of aphids in relation to host plants focusing on the role of the bacterial endosymbionts was investigated. Use of artificial diet including diverse antibiotics but also the comparison of proteomes related to whole aphid and respective purified bacterial symbionts were studied to identify the respective origin and function of proteins constituting the studied proteomes. Diverse methods including 2D-DIGE, liquid chromatography coupled with mass spectrometry and data bank investigations were developed. From the proteome investigation, characterisation of good and bad virus vectors was also performed in different aphid - plant - virus models. Particular proteins of interest were selected. This broad proteomic approach will be discussed as an interesting and reliable tool to study the biologically involved proteins from aphids in response to several environmental changes [less ▲]

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See detailBlocking lipid synthesis overcomes tumor re-growth and metastasis after anti-angiogenic therapy withdrawal.
Sounni, Nor Eddine ULg; Cimino, Jonathan ULg; BLACHER, Silvia ULg et al

in Cell Metabolism (2014), 20(2), 280-94

The molecular mechanisms responsible for the failure of antiangiogenic therapies and how tumors adapt to these therapies are unclear. Here, we applied transcriptomic, proteomic, and metabolomic approaches ... [more ▼]

The molecular mechanisms responsible for the failure of antiangiogenic therapies and how tumors adapt to these therapies are unclear. Here, we applied transcriptomic, proteomic, and metabolomic approaches to preclinical models and provide evidence for tumor adaptation to vascular endothelial growth factor blockade through a metabolic shift toward carbohydrate and lipid metabolism in tumors. During sunitinib or sorafenib treatment, tumor growth was inhibited and tumors were hypoxic and glycolytic. In sharp contrast, treatment withdrawal led to tumor regrowth, angiogenesis restoration, moderate lactate production, and enhanced lipid synthesis. This metabolic shift was associated with a drastic increase in metastatic dissemination. Interestingly, pharmacological lipogenesis inhibition with orlistat or fatty acid synthase downregulation with shRNA inhibited tumor regrowth and metastases after sunitinib treatment withdrawal. Our data shed light on metabolic alterations that result in cancer adaptation to antiangiogenic treatments and identify key molecules involved in lipid metabolism as putative therapeutic targets. [less ▲]

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See detailComparison of two FFPE preparation methods using label-free shotgun proteomics: Application to tissues of diverticulitis patients.
Quesada-Calvo, Florence; Bertrand, Virginie ULg; Longuespée, Rémi ULg et al

in Journal of proteomics (2014), 112C

Formalin-fixed paraffin-embedded (FFPE) specimens of patients are useful sources of materials for clinical research and have recently gained interest for use in the discovery of clinical proteomic ... [more ▼]

Formalin-fixed paraffin-embedded (FFPE) specimens of patients are useful sources of materials for clinical research and have recently gained interest for use in the discovery of clinical proteomic biomarkers. However, the critical step in this field is the ability to obtain an efficient and repeatable extraction using the limited quantities of material available for research in hospital biobanks. This work describes the evaluation of the peptide/protein extraction using FFPE sections treated by the following two methods before shotgun proteomic analysis: a commercial solution (FFPE-FASP) (filter aided sample preparation) and an antigen retrieval-derived protocol (On Slice AR). Their efficiencies and repeatabilities are compared using data-independent differential quantitative label-free analysis. FFPE-FASP was shown to be globally better both qualitatively and quantitatively than On Slice AR. FFPE-FASP was tested on several samples, and differential analysis was used to compare the tissues of diverticulitis patients (healthy and inflammatory tissues). In this differential proteomic analysis using retrospective clinical FFPE material, FFPE-FASP was reproducible and provided a high number of confident protein identifications, highlighting potential protein biomarkers. BIOLOGICAL SIGNIFICANCE: In clinical proteomics, FFPE is an important resource for retrospective analysis and for the discovery of biomarkers. The challenge for FFPE shotgun proteomic analysis is preparation by an efficient and reproducible protocol, which includes protein extraction and digestion. In this study, we analyzed two different methods and evaluated their repeatabilities and efficiencies. We illustrated the reproducibility of the most efficient method, FFPE-FASP, by a pilot study on diverticulitis tissue and on FFPE samples amount accessible in hospital biobanks. These data showed that FFPE is suitable for use in clinical proteomics, especially when the FFPE-FASP method is combined with label-free shotgun proteomics as described in the workflow presented in this work. [less ▲]

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See detailTissue Proteomics for the Next Decade? Towards a Molecular Dimension in Histology
Longuespée, Rémi ULg; Fléron, Maximilien; Pottier, Charles et al

in OMICS : A Journal of Integrative Biology (2014)

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See detailProteomic Analysis of the Reproductive Organs of the Hermaphroditic Gastropod Lymnea stagnalis Exposed to Different Endocrine Disrupting Chemicals
Giusti, Arnaud ULg; Leprince, Pierre ULg; Mazzucchelli, Gabriel ULg et al

in PLoS ONE (2013), 8(11), 81086

Many studies have reported perturbations of mollusc reproduction following exposure to low concentrations (ng/L range) of endocrine disrupting chemicals (EDCs). However, the mechanisms of action of these ... [more ▼]

Many studies have reported perturbations of mollusc reproduction following exposure to low concentrations (ng/L range) of endocrine disrupting chemicals (EDCs). However, the mechanisms of action of these molecules on molluscs are still poorly understood. Investigation of the modifications of protein expression in organisms exposed to chemicals using proteomic methods can provide a broader and more comprehensive understanding of adverse impacts of pollution on organisms than conventional biochemical biomarkers (e.g., heat-shock proteins, metallothioneins, GST, EROD). In this study we have investigated the impacts of four chemicals, which exhibit different endocrine disrupting properties in vertebrates, on the proteome of the hermaphroditic freshwater pulmonate gastropod Lymnaea stagnalis after 21 days of exposure. Testosterone, tributyltin, chlordecone and cyproterone acetate were chosen as tested compounds as they can induce adverse effects on the reproduction of this snail. The 2D-DIGE method was used to identify proteins whose expression was affected by these compounds. In addition to modifying the expression of proteins involved in the structure and function of the cytoskeleton, chemicals had impacts on the expression of proteins involved in the reproduction of L. stagnalis. Exposure to 19.2 μg/L of chlordecone increased the abundance of ovipostatin, a peptide transmitted during mating through seminal fluid, which reduces oviposition in this species. The expression of yolk ferritin, the vitellogenin equivalent in L. stagnalis, was reduced after exposure to 94.2 ng Sn/L of tributyltin. The identification of yolk ferritin and the modification of its expression in snails exposed to chemicals were refined using western blot analysis. Our results showed that the tested compounds influenced the abundance of yolk ferritin in the reproductive organs. Alteration in proteins involved in reproductive pathways (e.g., ovipostatin and yolk ferritin) could constitute relevant evidence of interaction of EDCs with reproductive pathways that are under the control of the endocrine system of L. stagnalis. [less ▲]

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See detailPolymer based intraocular lens adsorbome: a bottom up proteomics study
Bertrand, Virginie ULg; Huang, Yi-Shiang ULg; Mazzucchelli, Gabriel ULg et al

Conference (2013, September 08)

In the present work an optimized sample preparation protocol to identify and quantify the “adsorbomes” of hydrophilic and hydrophobic materials for IOLs known to have a higher or a lower incidence of PCO ... [more ▼]

In the present work an optimized sample preparation protocol to identify and quantify the “adsorbomes” of hydrophilic and hydrophobic materials for IOLs known to have a higher or a lower incidence of PCO, respectively was obtained. [less ▲]

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See detailIdentification of differential pattern of protein expression in canine osteoarthritis serum after anterior cruciate ligament transection: a proteomic analysis.
Gharbi, Myriam; Sanchez, Christelle ULg; Mazzucchelli, Gabriel ULg et al

in Veterinary journal (London, England : 1997) (2013), 197(3), 848-53

Osteoarthritis (OA) management remains a great challenge and there is considerable effort to understand its pathophysiology and to identify new therapeutic targets and biomarkers. Canine OA surgically ... [more ▼]

Osteoarthritis (OA) management remains a great challenge and there is considerable effort to understand its pathophysiology and to identify new therapeutic targets and biomarkers. Canine OA surgically induced by the transection of the anterior cruciate ligament (ACLT) is a widely used and relevant model. This study reports a proteome mapping of dog serum and an analysis of the differentially expressed proteins between before and after ACLT. In the first part of the study, 261 picked protein spots were identified from preparative 2D gels and 71 different proteins were identified among the 261 spots present on the reference map. Canine serum proteome mapping reveals the presence of proteins of interest, such as fetuin B, complement C3 and C1s and pregnancy zone protein. The comparison between serum from dogs before and after ACLT reveals the differential expression of several proteins that could play a key role in the pathogenesis of OA. A number of proteins, such as fetuin B and complement C3, were increased in dog OA serum whereas others, such as hyaluronan binding protein 2, inter-alpha-trypsin inhibitor H4 (ITIH4), complement C1s and C4 and haptoglobin were decreased. Some of these proteins could be candidate biomarkers for diagnosis, prognosis and treatment evaluation. The results of the study also reinforced the similarities between dog experimental OA and human cases of OA. [less ▲]

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See detailComparative analyses of salivary proteins from three aphid species
Vandermoten, Sophie ULg; Harmel, Nicolas; Mazzucchelli, Gabriel ULg et al

in Insect Molecular Biology (2013), under publication

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See detailIntraocular Lens Adsorbome: a Proteomic Study of Adsorbed Proteins onto Acrylic Materials and Its Implication in Secondary Cataract
Huang, Yi-Shiang ULg; Bertrand, Virginie ULg; Mazzucchelli, Gabriel ULg et al

Poster (2012, September 17)

The intraocular lens (IOL) is a polymer implant designed to replace the natural lens after cataract surgery. When the implant is introduced into the lens capsule, the polymer starts to interact with the ... [more ▼]

The intraocular lens (IOL) is a polymer implant designed to replace the natural lens after cataract surgery. When the implant is introduced into the lens capsule, the polymer starts to interact with the aqueous humour and the exchange of molecules between the solid and the liquid begins. The nature of exchange in water, ions, and biomolecules may result in several postoperative complications including glistening, calcification, and posterior capsular opacification. The posterior capsular opacification (PCO, also called “Secondary Cataract”) is raised from the over-growth of residual lens epithelial cells. The first step of the over-growth process of the cells is their adhesion to the deposited biomolecules, such as proteins involved in extra-cellular matrices. The purpose of this study is to identify the principal proteins adsorbed onto the acrylic polymers by mass spectrometry. The concept of adsorbome is to generate a list of adsorbed proteins to the hydrophilic and hydrophobic polymers, and then compare the difference to the original component of aqueous humour in order to see the affinity of individual protein to each material. Two kinds of hydrophilic and two kinds of hydrophobic acrylic polymers were tested for their adsorbomes by treating them with an aqueous humour analogue and the major adsorbed proteins were identified by mass spectrometry. Interestingly, the hydrophilic acrylic polymer shows a relative lower protein adsorption rate but shows a higher incidence of secondary cataract. This phenomenon implies the adsorbed proteins play a crucial role in progress of secondary cataract. [less ▲]

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See detailNanobodies as structural probes to investigate the mechanism of fibril formation by the amyloidogenic variants of human lysozyme
Dumont, Janice ULg; pardon, Els; Aumont-Nicaise, Magali et al

Poster (2012, June)

Six variants of human lysozyme (single-point mutatants I56T, F57I, W64R, D67H and double mutants F57I/T70N, W112R/T70N) are associated with a hereditary non-neuropathic systemic amyloidosis. These ... [more ▼]

Six variants of human lysozyme (single-point mutatants I56T, F57I, W64R, D67H and double mutants F57I/T70N, W112R/T70N) are associated with a hereditary non-neuropathic systemic amyloidosis. These proteins form extracellular amyloid fibrils that deposit in a wide range of tissues and organs such as liver, spleen and kidneys where they cause damages [1]. It was shown that the D67H and I56T mutations cause a loss in stability and more particularly a loss of global cooperativity of protein [1]. Consequently, under physiologically relevant conditions, these variants can transiently populate a partially unfolded state in which the beta-domain and the C-helix are cooperatively unfolded while the rest of the protein remains native like [1]. The formation of intermolecular interactions between the regions that are unfolded in this intermediate state is likely to be a fundamental trigger of the aggregation process that ultimately leads to the formation and deposition of fibrils in tissues. We have also shown that the binding of three variable domain of camelid antibodies (VHHs) - raised against the wild type human lysozyme inhibit in vitro the formation of amyloid fibrils by the lysozyme variants. These three VHHs bind on different regions of lysozyme and act as amyloid fibril inhibitor through different mechanisms [2, 3, and unpublished results]. In the present work, sixteen new VHHs specific of human lysozyme have been generated. Competition experiments have shown that they bind to five non-overlapping epitopes. We have demonstrated that five of these VHHs are able to bind lysozyme in conditions used for amyloid fibril formation, and interestingly two of them recognize two epitopes that are different from those of the three VHHs previously characterized [2, 3, and unpublished results]. The effects of these new VHHs on the properties of lysozyme variants such as stability, cooperativity and aggregation will be discussed. [1] Dumoulin, M., J.R. Kumita, and C.M. Dobson, Normal and aberrant biological self-assembly: Insights from studies of human lysozyme and its amyloidogenic variants. Acc Chem Res, 2006, 39(9), 603-610. [2] Dumoulin, M., et al., A camelid antibody fragment inhibits the formation of amyloid fibrils by human lysozyme. Nature, 2003, 424, 783-788. [3] Chan, P.H., et al., Engineering a camelid antibody fragment that binds to the active site of human lysozyme and inhibits its conversion into amyloid fibrils. Biochemistry, 2008, 47, 11041-11054. [less ▲]

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See detailIdentification and quantification of concentration-dependent biomarkers in MCF-7/BOS cells exposed to 17β-estradiol by 2-D DIGE and label-free proteomics
Collodoro, Mike ULg; Lemaire, Pascale ULg; Eppe, Gauthier ULg et al

in Journal of Proteomics (2012), in press

This paper reports the identification of biomarkers resulting from the exposure of MCF-7/BOS cells to 17β-estradiol (E2). The biomarkers were identified using 2 independent and complementary techniques, 2 ... [more ▼]

This paper reports the identification of biomarkers resulting from the exposure of MCF-7/BOS cells to 17β-estradiol (E2). The biomarkers were identified using 2 independent and complementary techniques, 2-D DIGE / MALDI-TOF peptide mass fingerprint, and 2-D UPLC-ESI MS/MS. These markers form a preliminary molecular signature that can be used when testing the estrogenic activity of xenobiotics, either pure or in mixtures. [less ▲]

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