Papers by Isabelle Fournier
Spinal cord injury (SCI) represents a major debilitating health issue with a direct socioeconomic... more Spinal cord injury (SCI) represents a major debilitating health issue with a direct socioeconomic burden on the public and private sectors worldwide. Although several studies have been conducted to identify the molecular progression of injury sequel due from the lesion site, still the exact underlying mechanisms and pathways of injury development have not been fully elucidated. In this work, based on OMICs, 3D matrix-assisted laser desorption ion-ization (MALDI) imaging, cytokines arrays, confocal imaging we established for the first time that molecular and cellular processes occurring after SCI are altered between the lesion proximity, i.e. rostral and caudal segments nearby the lesion (R1-C1) whereas segments distant from R1-C1, i.e. R2-C2 and R3-C3 levels coexpressed factors implicated in neurogenesis. Delay in T regulators recruitment between R1 and C1 favor discrepancies between the two segments. This is also reinforced by presence of neurites outgrowth inhibitors in C1, absent in R1. Moreover, the presence of immunoglobulins (IgGs) in neu-rons at the lesion site at 3 days, validated by mass spec-trometry, may present additional factor that contributes to limited regeneration. Treatment in vivo with anti-CD20 one hour after SCI did not improve locomotor function and decrease IgG expression. These results open the door of a novel view of the SCI treatment by considering the C1 as the therapeutic target. Molecular & Cellular Proteomics 15: 10.1074/mcp.M115.057794, 2641–2670, 2016. Spinal cord injury (SCI) 1 belongs to the serious, currently incurable disorders of the central nervous system (CNS), that are often accompanied by a permanent disability (1). Most SCI are related to traumatic spinal cord damages induced by road trauma, falls, or sport injuries (diving). Among the hallmark features of SCI is the axonal disruption in the spinal cord, which is often caused by fractured intervertebral disc or vertebrate. This primary event is followed by a progressive cascade of secondary deleterious reactions spreading to the adjacent spared tissue leading to a worsening of the neuro-logical status (2, 3). Although axonal regeneration is initiated, it is hampered by a combination of local factors that include severe inflammation, lack of trophic support and development of an inhibitory scar-forming environment. In fact, the regen-erative capacity of the central nervous system is particularly challenged in SCI as multiple cues converge to act as a chemical and physical barrier for the repair process (4, 5). It is now acknowledged that inflammation is one of the major key player that determines abortive axonal repair in SCI. Thus, although the immune response is recognized as primordial to preserve tissue homeostasis, the spatio-temporal course of inflammation in SCI is not favorable to axonal regeneration. Acute inflammation develops hours to days following initial spinal cord trauma and is triggered by the axonal damage and
Biochimica et Biophysica Acta (BBA) - General Subjects, 2016
The pathogenesis of acne vulgaris involves several phases including androgen-dependent hyper-sebo... more The pathogenesis of acne vulgaris involves several phases including androgen-dependent hyper-seborrhea, colonization by Propionibacterium acnes, and inflammation. Recent investigations have shown that in fact P. acnes provokes the activation of the inflammasome present in macrophages and dendritic cells. This signaling pathway leads to excessive production of interleukin IL-1β, a proinflammatory cytokine. Nevertheless, these well-studied phenomena in acne fail to elucidate the mechanisms responsible for the appearance of different lesions. We investigate response pathways for specific acne lesions such as microcysts and papules using shot-gun proteomic followed by systemic biology and transcriptomic approaches. Results show that most of the proteins identified as differentially expressed between the normal and acne tissue biopsies associated with the immune system response were identified as highly or exclusively expressed in the papule biopsies. They were also expressed in microcysts, but in lower amounts compared to those in papules. These results are supported by the identification of CAMP factor protein produced by P. acnes in microcysts, indicating its enhanced proliferation in this type of lesion CONCLUSIONS: As CAMP factor protein was not detected in papule biopsies, we can see a clear delineation in the stages of progression of acne pathogenesis, which begins with a hyphenated inflammatory response in the papule stage, followed by imbalance of lipid production, which in turn triggers the enhanced proliferation of P. acnes. We demonstrate that expression inflammation varies across the two types of lesions, suggesting different pathways enhanced as a function of the progression of P. acnes.
Biochimica et biophysica acta, Jan 24, 2016
An integrated diagnosis using molecular features is recommended in the 2016 World Health Organiza... more An integrated diagnosis using molecular features is recommended in the 2016 World Health Organization (WHO) classification. Our aim was to explore non-targeted molecular classification using MALDI mass spectrometry imaging (MALDI MSI) associated to microproteomics in order to classify anaplastic glioma by integration of clinical data. We used fresh-frozen tissue sections to perform MALDI MSI of proteins based on their digestion peptides after in-situ trypsin digestion of the tissue sections and matrix deposition by micro-spraying. The generated 70μm spatial resolution image datasets were further processed by individual or global segmentation in order to cluster the tissues according to their molecular protein signature. The clustering gives 3 main distinct groups. Within the tissues the ROIs (regions of interest) defined by these groups were used for microproteomics by micro-extraction of the tryptic peptides after on-tissue enzymatic digestion. More than 2500 proteins including 22 ...
Journal of Experimental Biology, 2011
Molecular and cellular Proteomics, 2006
MALDI direct analysis and MALDI imaging of tissues have shown to be a very powerful tool by local... more MALDI direct analysis and MALDI imaging of tissues have shown to be a very powerful tool by localizing molecules in tissue and by avoiding extraction, pre-purification, separation. Nevertheless, this new method requires new developments to increase sensitivity and specificity. We propose here a new concept and evolutions of each step of MALDI Imaging analysis. New matrices called Ionic matrices were synthesized to be especially well adapted for a good crystallization, sensitivity and resolution compared to the classical matrices. ...
54 th ASMS Conference Proceedings, 2006
New insights in sample preparation for MALDI Imaging and new developments to approach specific MA... more New insights in sample preparation for MALDI Imaging and new developments to approach specific MALDI imaging of the transcriptome. I Fournier, R Lemaire, M Wisztorski, J Stauber, O Jardin-Mathe, C Van Camp, M Deschamps, G Proess, R Day, M Salzet 54 th ASMS Conference Proceedings, 2006. Abstract not available. 17 Instruments and Measurements(SO).
Mol. Cell. Proteomics, 2006
Methods in Molecular Biology, 2010
MALDI imaging as a molecular mass spectrometry imaging technique (MSI) can provide accurate infor... more MALDI imaging as a molecular mass spectrometry imaging technique (MSI) can provide accurate information about molecular composition on a surface. The last decade of MSI development has brought the technology to clinical and biomedical applications as a complementary technique of MRI and other molecular imaging. Then, this IMS technique is used for endogenous and exogenous molecule detection in pharmaceutical and biomedical fields. However, some limitations still exist due to physical and chemical aspects, and sensitivity of certain compounds is very low. Thus, we developed a multiplex technique for fast detection of different compound natures. The multiplex MALDI imaging technique uses a photocleavable group that can be detect easily by MALDI instrument. These techniques of targeted imaging using Tag-Mass molecules allow the multiplex detection of compounds like antibodies or oligonucleotides. Here, we describe how we used this technique to detect huge proteins and mRNA by MALDI imaging in rat brain and in a model for regeneration; the leech.
Mol. Cell. Proteomics, 2006
PROTEOMICS - Clinical Applications, 2013
OMICS: A Journal of Integrative Biology, 2014
Histochemistry and Cell Biology, 2012
Journal of Proteomics, 2013
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Papers by Isabelle Fournier