summary - ecole doctorale biologie santé (bs)...3 tuesday, december 10, 2019 8h30-9h30 welcome...
TRANSCRIPT
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Summary
Program………………………………………………… P.3
Oral Communication………………………………….. P.5
Poster…………………………………………………… P.33
List of participants…………………………………….. P.47
Practical information………………………………….. P.51
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Tuesday, December 10, 2019
8h30-9h30 Welcome reception, distribution of bags and badges
9h30-9h45 Opening plenary: Laurent Beck, Director of UBL ED-BS
9h45-
10h30
Pr. Frédéric Benhamou, Ex. Vice-President Research and Innovation: "Inter et Transdisciplinarity", Informatic
department; UMR_6004 Laboratoire des Sciences du Numérique de Nantes
10h30-
11h15Coffee break and poster session
Session 1: Bioinformatic & biostatistic
11h15 Manon Pruvost-Couvreur, Laberca, U1329, Oniris, Nantes : Modelling approach to assess lifetime dietary risk
due to cadmium exposure
11h30 Noriane Cognez, IRSET, U1085, Rennes : Determinants of maternal exposure to pesticides measured in hair:
The French ELFE birth cohort
11h45 Maël Conan, IRSET, U1085, Rennes : Predictive approach to assess the genotoxicity of environmental
contaminants during liver fibrosis
12h Louis Marage, LTSI, U1099, Rennes : A bone-marrow-optimized quantitative MRI protocol: towards better patient
follow-up
12h15-14h Lunch
Session 2: Oncology, chemotherapy & radiotherapy
14h Amine Maarouf, CRCINA, U1232, Angers : The role of Agr2 in chemotherapy-induced senescence and senescence
escape
14h15 Kévin Bevant, NuMeCan, U1241, Rennes : TFOX, a novel TGF-β target gene, promotes epithelial-
mesenchymal transition and is associated with poor prognosis in human hepatocellular carcinoma
14h30 Coralie Petit, CRCINA, U1232, Angers : Regulation of senescence escape by TSP1 and CD47 following
chemotherapy treatment
14h45 Marion Berdal, CRCINA, U1232, Nantes : A universal method for the radioiodination and astatination of
antibodies: easy access to I/At based theranostic tools
15h-15h45 Coffee break and poster session
15h45-
16h30
Dr Erell Le Deun, Biogenouest network facilitator,: "Biogenouest: the life science and environment core facility
network in Western France" Biogenouest
Session 3: Medicine & physiopathologies
16h30 Amal Ben Abid, LTSI, U1099, Rennes : Influence of LVAD inflow cannula angulation on blood stagnation using
CFD computation
16h45 Jacques Tomasi, LTSI, U1099, Rennes : Clinical impact of simulation in aortic dissection
17h Rosy Ghanem, GFGB, U1078, Brest : New ramified cationic amphiphiles as novel efficient gene delivery systems
for cystic fibrosis by aerosol
17h15 Lise Piquilloud Imboden, Mitovasc, U1083, Angers : Information conveyed by electrical diaphragmatic activity
during unstressed, stressed and assisted spontaneous breathing: a physiologic study
17h30 Clara Savary, IGDR, U6290, Rennes : Deciphering the genetic etiology of pediatric cancers through an integrative
gene network approach
19h-22h Social event
11h15-
12h15
14h-15h
16h30-
17h45
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Wednesday, December 11, 2019
9h-9h15 Welcome reception
9h15-10hDr. Damien Derouet, Manager of Le Mans Innovation: "Support for founding innovative companies for doctorates",
Le Mans Innovation
Session 4: Microbiology & nutrition
10h Mélanie Foulon, CRCINA, U1232, Angers : Ketogenic diet benefits against Mycobacterium ulcerans infection: keys
toward wound management improvement in Buruli ulcer
10h15 Morgane Frapin, PhAN, U1280, Nantes : Maternal Malnutrition and Hypothalamic Development
10h30 Typhaine Violo, UFIP, U6286, Nantes : Generation of homogenous monovalent and trivalent glycoconjugate
vaccines against Streptoccocus pneumoniae using unnatural amino acid incorporation
10h45 Sophie Reissier, BRM, U1230, Rennes : Development of a new murine model for Enterococcus faecium
intestinal colonization
11h-11h30 Coffee break and poster session
Session 5: Chemistry
11h30 Kevin Matha, MINT, U1066, U6021, Angers : Transposition from a batch to continuous formulation process of
pentamidine-loaded nanopolyplexes to treat Leishmaniasis
11h45 Mariane Pourchet, Laberca, U1329, Oniris, Nantes : Development and application of a non-targeted approach to
characterise human exposure to halogenated chemicals of concern in human breast milk
12h Sarine El Daouk, IICiMED, EA1155, Nantes : Exposure of the Lebanese population to aluminum and analysis of
food determinants
12h15 Claire Gazaille, MINT, U1066, U6021, Angers : New generation of glioblastoma-targeted lipid nanocapsule
hydrogel: a sustained and specific drug delivery system
12h30-14h Lunch
Session 6: Immunology, biology & fundamental research
14h Yodit Feseha, CRTI, U1064, Nantes : Tribbles Homolog 1 is a negative regulator of FOXP3 in regulatory T cells
14h15 Dhon Roméo Makanga, CRCINA, U1232, Nantes : Genetic and molecular basis of the phenotypic and functional
structuration of the NK cell repertoire: implication in the context of acute leukaemia
14h30 Julie Pabois, TENS, U1235, Nantes : Pro-inflammatory stimuli increase ICAM-1 expression in enteric glial cells
and favor T cell adhesion
14h45 Morgane Pengam, ORPHY, EA4324, Brest : Molecular responses involving in mitochondrial biogenesis depend
on the training type in the trout red muscle
15h Alexandre Villard, SOPAM, U1063, Angers : Feces-derived extracellular vesicles from patients with liver diseases
cause barrier dysfunctions by reducing ZO-1 and occludin expressions via non-muscular light chain kinase-dependent
pathway
15h15 Nettie Van Meteren, IRSET, U1085, Rennes : Polycyclic aromatic hydrocarbons trigger a hepatocyte release of
pro-apoptotic extracellular vesicles
15h30-
16h15Coffee break and poster session
16h15-17h Awards and closing ceremony
14h-15h30
11h30-
12h30
10h-11h
5
Oral communication
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Modelling approach to assess lifetime dietary risk due to cadmium exposure
Pruvost-Couvreur Manon1,2, Rivière Gilles2, Béchaux Camille2, Le Bizec Bruno1
1LABERCA, INRA UMR1329, Oniris, Route de Gachet - CS 50707 – F-44307 Nantes Cx 3
2Risk Assessment Department - French Agency for Food, Environmental and Occupational
Health and Safety, Maisons-Alfort, France
Introduction: Cadmium is a heavy metal present in food, inducing numerous adverse health
effects. Because it accumulates in the human organism through life, the knowledge related to
the lifetime dietary exposure is crucial. However, dietary exposure to chemicals is classically
assessed based on single measurements of food consumption and contamination. According to
this method, individual evolutions of eating habits, of food contamination and lifetime
accumulation of chemicals in the body, are not considered. In this study, we present a new
methodological approach allowing simulating lifetime exposure trajectories based on the
example of cadmium dietary exposures. An interpretation of these lifetime trajectories in terms
of risk assessment is also proposed.
Method: Because sociodemographic parameters explain a part of the dietary exposure, virtual
individuals with preset lifetime characteristics are simulated. Then, dietary exposures to
cadmium are predicted from these individual parameters. Evolution of cadmium exposure in
last decades is studied and a physiologically based toxicokinetic (PBTK) model is used to assess
the accumulation of cadmium in the body for each virtual individual. With the aim of evaluating
health risk related to lifetime cadmium exposures, the trajectories have been compared with
several critical thresholds.
Results: Cadmium exposures are significantly correlated with the body mass index, the gender,
the region of residence, the household income and the education level. Simulated lifetime
concentrations of cadmium in the body highlight the existence of trajectories exceeding the
critical thresholds. Furthermore, because a direct relation between cadmium concentration in
the body and renal adverse effects is known, the prediction of the impact of cadmium exposure
on renal activity becomes achievable. Thus, severe renal tubulopathy cannot be excluded for
some virtual individuals, even though effects occur in the vast majority at an old age.
Discussion and conclusions: Despite several regulations limiting the use of cadmium in
industry, this metal is still present in the environment and finally in food, thus exposing
consumers. The proposed approach highlights the relevance of studying lifetime trajectories,
by identifying “at-risk subpopulations” and allowing the quantification of effects associated
with cadmium. Because only dietary exposures are considered in this study, whereas food is
not the only source of exposure to cadmium, this situation is even more serious for individuals
exposed via smoking or working activities. Future work could be interested in combining the
different sources of exposure in lifetime risk assessment. Furthermore, this approach can be
extended to other chemicals, in particular bioaccumulative contaminants.
Keywords: Lifetime dietary exposure Cadmium Modelling
7
Determinants of maternal exposure to pesticides measured in hair: The French ELFE
birth cohort
Cognez Noriane1, Chevrier Cécile1, Béranger Rémi2, Appenzeler Brice3
1UnivRennes, Inserm, EHESP, IRSET-UMR_S 1085, Rennes, France
2UnivRennes, CHU Rennes, Inserm, EHESP, IRSET-UMR_S 1085, Rennes, France
3Luxembourg Institute of Health, Luxembourg
Context: Various studies have suggested adverse health outcomes related to pesticide
exposures. There is however still gaps in knowledge, especially for non-occupational exposure
and modern pesticides, due to challenges in assessing such exposures. The development and
validation of indirect exposure indicators is a pre-request to develop this area of
epidemiological research.
Objective: To compare non-occupational pesticide exposure levels estimated though indirect
exposure indicators with measures performed in women’s hair, and to identify their major
environmental and lifestyle determinants.
Methods: We selected 311 women living in northeastern and southwestern France in 2011 from
the Elfe birth cohort. We measured 140 pesticides and pesticide metabolites in 9 cm long hair
samples collected at delivery. Non-occupational pesticide exposures during pregnancy were
estimated through self-reported domestic uses, GIS-estimated amount of agricultural pesticide
uses within 1000-m distance from home, and estimated dietary intakes were studied, based on
known pesticide usages in 2011. For the 28 chemicals with detection frequency above 70%, we
used a backward selection strategy to detect associations between log-transformed hair
concentrations and potential socio-economic determinants or indirect exposure indexes,
separately. Linear or tobit regression modeling was used according to chemical detection rates.
Results: Median concentrations of pesticides ranged from 0.03 pg/mg of hair for metolachlor
to 37.93 pg/mg for permethrin. Among mothers, 27% declared domestic uses of pesticides, 83%
had agricultural crops within 1000-m from their home. Estimated dietary intakes were non-null
for 30% to 100% of women for 21 pesticides. Smoking during pregnancy, a lower educational
level, and maternal age, BMI and parity were associated to an increased hair concentration of
some organochlorine, organophosphorous and pyrethroid insecticides and metabolites, one
carbamate and one azole fungicides, and three chemicals from acid herbicides family. Domestic
uses of pesticides products against fleas and ticks and against crawling insects were associated
with increased hair concentration of some pyrethroid insecticides, fipronil and its main
metabolite fipronil sulfone. Our results show moreover sparse negative associations with
domestic uses against flying insects and to treat outdoor plants. For several compounds, our
results also suggests associations between the amount of agricultural pesticide uses nearby
households and the women’s hair concentration, especially for prosulfocarb. Associations with
estimated dietary intakes of pesticides remains more inconsistent.
Conclusions: Our results suggests some consistencies between non-occupational pesticide
exposure levels assessed using different indirect indicators and their concentration in women’s
hair. We also identified several personal and socioeconomic factors associated to the pesticide
exposure level.
Keywords: Pesticides, Hair, Determinants of exposure
8
Predictive approach to assess the genotoxicity of environmental contaminants during liver
fibrosis
Maël Conan1
1IRSET
The liver plays a major role in the biotransformation (or metabolic activation) of xenobiotics
(drugs, pollutants, pesticides, food additives...). However, the metabolism of chemical
compounds can lead to the formation of reactive metabolites that can bind to DNA and form
DNA adducts, thus causing genetic toxicity leading to mutations. In this context, my project
aims to develop predictive models of the genotoxicity of environmental contaminants in
humans based on the reconstruction of metabolic networks. Among the contaminants of current
concern, we focus on heterocyclic aromatic amines (HAAs) produced by cooked meat or fish,
exhaust gas or cigarettes smoke and classified as possibly carcinogenic.
Based on the knowledge about HAAs metabolism, I developed a modeling approach using the
integration of predictive tools for site of metabolism (Way2Drug, Xenosite and Fame3) and
Bayesian methods applied to networks. The validation of the model is currently in progress and
require the use of biological observations. For that I use gene expression data from enzymes
involved in HAA metabolism reactions. These data come from RNA seq analyses of liver
samples from 294 patients with hepatocellular carcinoma (TCGA database) and for whom liver
metabolism is disrupted.
Keywords: Metabolic network, Bayesian Model, Liver Metabolism, DNA adducts, Bayesian
network
9
A bone-marrow-optimized quantitative MRI protocol: towards better patient follow-up.
Louis Marage1, Giulio Gambarota1, Jeremy Lasbleiz1, Mathieu Lederlin1, Hervé Saint-
Jalmes1.
1: Univ Rennes, CHU Rennes, CLCC Eugène Marquis, Inserm, LTSI - UMR 1099, F-35000
Rennes, France.
Introduction: Recent progresses on quantification of MRI vertebral bone marrow biomarkers
(VBMBs), allow robust quantification method with spatially resolved sequences. A
comprehensive MRI tissue characterization of vertebral bone marrow includes the
measurement of the following biomarkers: fat fraction (FF), T1 and T2* relaxation times of the
water and fat components (T1W, T1F, T2*W, T2*F), IVIM (IntraVoxel Incoherent Motion)
diffusion (D) and perfusion parameters (perfusion fraction f and pseudo-diffusion coefficient
D*). In the current study, we sought to investigate the effect of spatial heterogeneity of bone
marrow within a single vertebra on these seven VBMBs.
Material and Methods: Two regions-of-interest (ROIs), the anterior and posterior area of lumbar
vertebrae, were chosen for investigation. MRI experiments were carried out in 14 young healthy
volunteers at 1.5 T. The RESOLVE diffusion-weighted sequence was used for the
measurements of the IVIM parameters and the VIBE-Dixon sequence for the measurements of
FF, T1W, T1F, T2*W and T2*F. The entire MRI protocol lasted less than 6 minutes and the
protocol was repeated two times. ROI measurements in anterior region were compared to those
in the posterior region, with the Wilcoxon signed-rank test.
Results: A significant difference in the values of FF, f, T1F, T2*W and D was observed between
the anterior and posterior region. The regional difference in FF, f and T2*W can be ascribed to
the difference of tissue characteristics, such as the trabecular bone density and the vascular
network, within vertebrae.
Discussion: The regional variation of VBMBs observed in the current study indicates that care
should be taken in reproducing the same ROI location along a longitudinal study.
Furthermore, the MRI protocol presented here allows for the measurement of seven VBMBs in
less than 6 minutes. It could be of interest for longitudinal studies of bone marrow diseases,
such as myeloma, during the patient treatment and follow up.
Keywords: MRI, Magnetic Resonance Imaging, Biomarkers, Bone Marrow, Relaxometry,
Diffusion Weighted Imaging, IVIM
10
The role of Agr2 in chemotherapy-induced senescence and senescence escape
Maarouf Amine1
1INSERM U1232 Equipe 12
Agr2 is a Protein Disulphide Isomerase (PDI) mostly found in the endoplasmic reticulum ER.
As other PDI, Agr2 has a Thioredoxine domain which has a major role in protein maturation
and stabilization during their synthesis. This domain can also enable Agr2 linking to other
proteins and homodimer formation. Agr2 is not an ER-resident protein, it can also be found in
the cytoplasm or secreted in the extracellular compartment, where it can take part in other
mechanisms. Several studies described Agr2 as a pro-oncogenic protein since it is
overexpressed in many types of cancer. It was shown that Agr2 overexpression leads to cells
proliferation and invasion, metastasis formation and resistance to treatments. These effects were
either due to its intracellular or the extracellular form. It has been also reported that Agr2 acts
as a negative regulator of the tumor suppressor p53, and its downregulation by siRNA induce
the expression of senescence markers such as p16 and p21. Thus, Agr2 could be a new marker
and a key player in senescence failure.
One of the main research axes in our laboratory is quantitative proteomic studies, which allow
us a better understanding of tumor aggressiveness and patients relapse. Using ELISA assay, we
found a high concentration of Agr2 in serums from breast cancer patients. This amount was
even higher in patients with metastasis. Besides that, we analyzed tumors from TNBC patients
by mass spectrometry and we discovered that overexpression of Agr2 is negatively correlated
with the expression of p16.These results led us to explore the role of Agr2 in relapse process
and escaping tumor-suppressive mechanisms such as senescence.
We therefore used a model of chemotherapy-induced senescence (CIS) escape. MCF7 cells
were treated with Doxorubicin to enter senescence and then stimulated to promote cells’
emergence. In this model, Agr2 protein levels were downregulated during senescence and
overexpressed during cell emergence. To further investigate the role of Agr2 in this model, we
silenced its expression in early emergence using siRNA. Results show that the lack of Agr2
reduced significatively the number of emerging clones. Taken together, these preliminary data
confirm the role of Agr2 in aggressiveness shown by others, as well as its involvement in the
CIS escape.
Keywords: Agr2, Senescence, p21, Akt
11
TFOX, a novel TGF-β target gene, promotes epithelial-mesenchymal transition and is
associated with poor prognosis in human hepatocellular carcinoma
Kevin Bevant1, Gaelle Angenard1, Betty Maillot1, Stefano Caruso2,3, David Gilot4, Jessica
Zucman-Rossi2,3,5, Cedric Coulouarn1
1UMR1241 NuMeCan (Nutrition, Metabolism and Cancer), Inserm, Rennes, France, 2Centre
de Recherche des Cordeliers, Sorbonne Universités, Inserm, UMRS-1138, F-75006 Paris,
France, 3Functional Genomics of Solid Tumors, USPC, Université Paris Descartes, Université
Paris Diderot, Université Paris 13, Labex Immuno-Oncology, équipe labellisée Ligue Contre le
Cancer, F-75000 Paris, France, 4Univ Rennes, CNRS, IGDR [(Institut de génétique et
développement de Rennes)]-UMR 6290, ARC Labelled team, F-35000, Rennes, France;
5European Hospital Georges Pompidou, AP-HP, F-75015, Paris, France
Liver cancers is the fourth leading cause of cancer-related death worldwide and the sixth most
commonly diagnosed cancer. Among them, hepatocellular carcinoma (HCC) is the most
common liver primary tumor (75-85% of cases).This made HCC a major public health
consideration. However, there is no curative therapy except surgery against this cancer. HCC
usually occurs in patient with underlying chronic liver disease leading to liver fibrosis such as
HBV or HCV infection, metabolic syndrome, alcoholism or aflatoxin-contaminated foodstuffs.
In this context, the inflammatory cytokine Transforming Growth Factor β (TGF-β) plays an
important role in HCC development. However TGF-β action in HCC is complex because it
exhibits both oncogenic and anti-tumorigenic properties. In the early stage of the disease, TGF-
β acts as a tumor suppressor by inhibiting cellular proliferation but in the advanced stage, his
action change toward a pro-metastatic action, essentially by promoting epithelial-mesenchymal
transition (EMT). The mechanisms underlying this switch of action of the TGF-β pathway are
yet not fully understand. Identification of new factors involved in the TGF-β pathway could
explain this functional duality. In this regard, we identified the transcription factor TFOX as a
new target of the TGF-β pathway that mediates the TGF-β pro-metastatic properties.
Gene expression profiling and RT-qPCR were used to identify and to validate TFOX as a novel
TGF-β target gene in HCC cell lines. Stable cell lines KO (CRISPR/cas9) or overexpressing
TFOX (lentiviral construct) were generated and used in molecular and functional analysis to
determine TFOX function. Clinical relevance of TFOX in human cancers was evaluated by
integrative genomics and analysis of TCGA datasets.
Our results show that TFOX is novel canonical TGF-β target gene. It is expressed and inducible
by TGF-β in mesenchymal HCC cell lines. It reduces adhesion, increases migration and
promotes EMT by induction of EMT markers (SNAI1, VIM). In human HCC, TFOX correlates
with VIM expression and his highly expressed in subtype of tumor associated with poor
differentiation and stemness markers. Moreover, TFOX expression is associated with a reduced
survival and is a marker of poor prognosis, not only in HCC but also in colon, stomach and
kidney cancer.
In summary, TFOX is a new TGF-β target gene which promotes EMT and cell migration in
HCC and is a marker of poor prognosis in several cancers. The identification of tumors
expressing TFOX and so in which the TGF-β pro-metastatic arm is active could help us
screening patient who may benefits from TGF-β inhibitors based therapy.
Keywords: Hepatocellular carcinoma, Transforming Growth Factor beta, Epithelial-
mesenchymal transition
12
Regulation of senescence escape by TSP1 and CD47 following chemotherapy treatment
Petit Coralie1
1INSERM U1232 Team 12
Senescence is a tumor-suppressive mechanism induced by telomere shortening, oncogenes, or
chemotherapy treatment. Although it is clear that this suppressive pathway leads to a permanent
arrest in primary cells, this might not be the case in cancer cells that have inactivated their
suppressive pathways. We have recently shown that subpopulations of cells can escape
chemotherapy-mediated senescence and emerge as more transformed cells that induce tumor
formation, resist anoikis, and are more invasive. In this study, we characterized this emergence
and showed that senescent cells favor tumor growth and metastasis, in vitro and in vivo.
Senescence escape was regulated by secreted proteins produced during emergence. Among
these, we identified thrombospondin-1 (TSP1), a protein produced by senescent cells that
prevented senescence escape. Using SWATH quantitative proteomic analysis, we found that
TSP1 can be detected in the serum of patients suffering from triple-negative breast cancer and
that its low expression was associated with treatment failure. The results also indicate that
senescence escape is explained by the emergence of CD47low cells that express a reduced level
of CD47, the TSP1 receptor. The results show that CD47 expression is regulated by p21waf1.
The cell cycle inhibitor was sufficient to maintain senescence since its downregulation in
senescent cells increased cell emergence. This leads to the upregulation of Myc, which then
binds to the CD47 promoter to repress its expression, allowing the generation of CD47low cells
that escape the suppressive arrest. Altogether, these results uncovered a new function for TSP1
and CD47 in the control of chemotherapy mediated senescence.
Keywords: Chemotherapy-induced senescence, Escape, TSP1, CD47
13
“A universal method for the radioiodination and astatination of antibodies: easy access
to I/At based theranostic tools”
Marion Berdal1, Laurent Navarro1, Cyrille Alliot1,2, Mikaël Croyal3, Michel Chérel1, Alain-
Faivre Chauvet1, Jean-François Gestin1, François Guérard1
1CRCINA, Inserm, CNRS, Université de Nantes, Nantes, France, 2Arronax GIP, Saint-
Herblain, France, 3Plateau de Spectrométrie de Masse du CRNH, UMR 1280, Nantes, France
INTRODUCTION: Astatine-211 and radioiodine are increasingly studied for
radioimmunotherapy and nuclear imaging. However, to associate them to cancer targeting
monoclonal antibodies (mAbs), current approaches exhibit limitations such as suboptimal and
inconsistent radiochemical yields (RCYs). Electrophilic radiohalogenation in two[1] or one[2]
step presented major inconveniences: use of halogens in their electrophilic form, which is
particularly unstable in the case of astatine, and toxic organostannic precursors. Furthermore,
the two-step method results in suboptimal RCYs, while the one-step method is not applicable
to radioiodine since electrophilic iodine reacts competitively with tyrosines, forming an
unstable bond. A two-step nucleophilic radiohalogenation was recently developed,[3] which
improved the robustness of the procedure, but there is still room for a significant improvement
of the global RCY by reducing the number of radiosynthesis steps to only one.
OBJECTIVE: To overcome these limitations we investigated the possibility to develop a new
method of direct radiohalogenation by a nucleophilic approach, that would be applicable to both
astatine and radioiodine, and if possible using a precursor of lower toxicity. Our strategy was
based on mAbs pre-conjugated with arylboronic acids, reported for radiohalogenation of small
organics molecules.[4], [5], [6] Since the reported conditions are not compatible with mAbs
(organic solvent, high temperature), the challenge was to adapt this chemistry in aqueous
medium via a model compound (4-chlorophenylboronic acid) before transferring it to mAbs by
optimizing the nature of the catalyst, ligand, buffer and pH of reaction.
RESULTS: The model compound gave quantitatives RCYs for both 125I and 211At using
Cu(OTf)2pyr4 and 1,10-phenanthroline in TRIS buffer at pH 6. Transposition to mAbs gave
RCYs ≥ 85 % with immunoreactivities > 85 % for both 125I and 211At.
CONCLUSION: We described the first method of antibody direct radiolabeling applicable to
both astatine and radioiodine with preservation of immunoreactivity. Compared to the two-step
method, the global RCYs were nearly doubled and the procedure duration divided by two.
These results should facilitate the transfer of astatine-211 to the clinic and accelerate
development of theranostic tools using iodine and astatine radioisotopes.
REFERENCES [1] Zalutsky et al, Proc. Natl. Acad. Sci. USA, 86, 7149 (1989), [2] Lindegren
et al, J. Nucl. Med., 49, 1537 (2008), [3] Guérard et al, Bioorg. Med. Chem., 25, 5975 (2017),
[4] Mossine et al, Org. Lett., 17, 5780 (2015), [5] Zhang et al, Chem. – Eur. J., 22, 16783
(2016), [6] Reilly et al, Org. Lett., 20, 1752 (2018)
Keywords: Astatine-211, iodine-125, boronics acids, radiolabeling, radiochemistry, antibody,
bioconjugation
14
Influence of LVAD inflow cannula angulation on blood stagnation using CFD
computation
Amal BEN ABID1, Pascal HAIGRON1 and Erwan FLECHER1
1Univ Rennes, CHU Rennes, INSERM, LTSI – UMR 1099, F-35000 Rennes, France
Introduction: Left Ventricular Assistant Device (LVAD) is used to substitute heart
transplantation. Computational Fluid Dynamics (CFD) might be used to anticipate blood
stagnation due to inflow cannula (IC) orientation. Recent results [1-3] obtained on a limited
number or range of angular configurations, were not sufficiently demonstrative. This study
investigates the ability of CFD to establish the link between IC angulation and blood stagnation.
Method: Since 3D models are time consuming which limit the number of in-silico experiments,
a generic 2D model was elaborated. The left ventricle (LV) was modeled as a rigid ellipsoid
flattened by the mitral valve and the IC was defined as a mass flow outlet. Two different flow
rates were considered: optimal (5L/min) and reduced (3L/min). Blood was considered
Newtonian with laminar flow. Five different cannula angulations (0° 40°) were investigated.
Stagnation was analyzed using flow velocity and residual ink concentration (RIK) defined as a
scalar. The simulation consisted of three phases: Initialization, filling ventricle with ink and
clearing.
Results: The results showed that the velocity is low within the apex and close to LV wall. Those
regions may be considered as potential stagnation regions. RIK is located at the ventricular apex
for all configurations. The more the cannula angulation is important the more the residual ink
stagnation is important.
Conclusion: The results showed that CFD can be an effective tool for analyzing the influence
of IC angulation on blood stagnation. An advanced marker of coagulation risk may be devised
by combining velocity and RIK. Patient-specific 3D model has still to be considered for surgical
planning.
References [1] S. Collin, “Preoperative planning and simulation for artificial heart implantation
surgery” Thèse de l’Université Rennes1, Mars 2018, [2] A. R. Prisco, A. Aliseda, J. A.
Beckman, N. A. Mokadam, C. Mahr, and G. J. M. Garcia, “Impact of LVAD Implantation Site
on Ventricular Blood Stagnation,” ASAIO J., vol. 63, no. 4, pp. 392–400, 2017, [3] Venkat
Keshav Chivukula, Jennifer A. Beckman, Anthony R. Prisco, Todd Dardas, Shin Lin, Jason W.
Smith, Nahush A. Mokadam, Alberto Aliseda, Claudius Mahr, “Left Ventricular Assist Device
Inflow Cannula Angle and Thrombosis Risk,” Circ. Hear. Fail., vol. 11, no. 4, pp. 1–9, 2018.
Keywords: left ventricular assist device, inflow cannula, blood stagnation, cannula angulation
15
Clinical impact of simulation in aortic dissection
Tomasi Jacques1, Shao Clémentine2, Lucas Antoine1, Haigron Pascal3, Verhoye Jean-
Philippe1
1CHU de Rennes, 2Ansys, 3Inserm,
Introduction: Regular monitoring of uncomplicated type B aortic dissection is essential because
25 to 30% will progress to aneurysmal form. The predictive factors of this evolution are not
clearly defined, but they seem to be correlated with hemodynamic data.
Hypothesis: Our goal is to create a patient-specific and real-time model of numerical simulation
of the hemodynamics of uncomplicated type B aortic dissections in order to predict the
evolution of these pathologies for earlier treatment.
Method: This model consists in a coupling 0D (hydraulic-electric analogy) - 3D (CT
angiography segmentation) of the aortic arch with optimization by comparison to the 2D Phase
Contrast MRI data and using Reduced Order Models to drastically reduce computing times. We
tested our model on a healthy and a dissected patient. Then we realized different systolic blood
pressure scenarios for each case, which we compared.
Results: In the dissected patient, the blood pressure at the false lumen wall was less important
than the true lumen. Furthermore, the aortic wall shear stress and the velocity fields in aorta
increase at the entry and re-entry tears between the two lumens. The simulation of different
blood pressures scenarios shows a decrease in all these three parameters related to the decrease
of the systolic blood pressure.
Conclusion: Our model provides reliable patientspecific and real-time 3D rendering. It has also
allowed us to realize different flow variation scenarios to simulate different clinical conditions
and to compare them. However, the model still needs improvement in view of a daily clinical
application.
Keywords: Assessment in Health Technology, Surgery, Medical Imaging, Computer-Aided
Diagnosis
16
New ramified cationic amphiphiles as novel efficient gene delivery systems for cystic
fibrosis by aerosol.
Ghanem Rosy1, Bouraoui Amal2, Berchel Mathieu2, Le Gall Tony1, Lozach Olivier2, Jaffres
Paul-Alain2, Montier Tristan1
1«Transfert de gènes et thérapie génique», INSERM UMR 1078, IBSAM, UFR Médecine et
Sciences de la Santé, CHRU Brest
2«Phosphore et vectorisation», CEMCA UMR CNRS 6521, Université de Brest, IBSAM
Cystic fibrosis (CF) is an autosomal recessive genetic disorder that affects the gene encoding
for the Cystic Fibrosis Transmembrane conductance Regulator (CFTR, chloride channel). This
alteration induces a dysfunction of ions transportation and mucus dehydration. Mucosal
accumulation leads to bacterial colonization causing lung failure which is remaining the main
cause of death today. One solution to restore CFTR expression consists to introduce a transgene
encoding CFTR directly toward the airway epithelium. Due to its safety, aerosol represents the
most suitable choice to achieve pulmonary tract. Non-viral vectors, like cationic lipids, have
the ability to compact and protect nucleic acids to form lipoplexes. Despite a low transfection
efficiency in comparison with viral vectors, they present the advantage to be re-administrable
due to their poor immunogenicity. Repeat deliveries are necessary required because of the
transient transgene episomal expression and the renewal of epithelial airway. One of them,
GL67A (Alton et al, Lancet 2015) was recently tested in clinic with a certain success. Yet, the
improvement of delivery synthetic vectors is required to deeply change the CF phenotype and
to equal the efficiency of viral vectors. Hence, we focused on the incorporation of a ramified
poly carbons chain on the lipid domain and evaluated its transfection capacity by aerosol (alone
or mixed with DOPE). This assays were performed using 1mg of an optimized CpG free
plasmid encoding a luciferase reporter gene (Hyde et al, Nat Biotech, 2008) on four different
pulmonary cell lines (16HBE14o-, A549, CFBE41o- and Calu-3). In order to determine their
efficiency for gene transfection, the reporter gene activity was evaluated according to the
expression of luciferase 24h after aerosol. Results shown a transfection efficiency between 106
to 108 RLU/mg of proteins (depending on the cell line) with a low cytotoxicity. The size of
lipoplexes were measured before aerosol around 250 nm but increase after aerosol. We also
reported that the addition of DOPE is beneficial for an efficient formation of the complexes.
Indeed, 1:1 cationic lipid / DOPE ratio mol:mol showed a better transfection efficiency in
comparison with the cationic lipid alone. This new cationic lipid seems to be promising for
gene delivery in the airway epithelium. However, one of the greatest challenge for CF gene
therapy is to overcome the mucus barrier which is impeding lipoplexes to reach pulmonary
cells. Ongoing investigations are running to determine the ability of this new ramified cationic
amphiphiles to penetrate the CF mucus.
Keywords: Cystic Fibrosis, Gene therapy, Non-viral vector, Aerosol
17
Information conveyed by electrical diaphragmatic activity during unstressed, stressed
and assisted spontaneous breathing: a physiologic study.
Piquilloud Imboden Lise1, Beloncle François1, Richard Jean-Christophe2, Mancebo Jordi3,
Mercat Alain1, Brochard Laurent4
1CHU Angers, 2Hôpital Général d’Annecy, 3Sant Pau Hospital, 4St Michael’s Hospital Toronto
Background: The electrical activity of the crural diaphragm (Eadi), a surrogate of respiratory
drive, can now be measured at the bedside in mechanically ventilated patients with a specific
catheter. The expected range of Eadi values under stressed or assisted spontaneous breathing is
unknown. This study explored Eadi values in healthy subjects during unstressed (baseline),
stressed (with a resistance) and assisted spontaneous breathing. Relation between Eadi and
inspiratory effort was analyzed.
Methods: Thirteen healthy male volunteers were included in this randomized crossover study.
Eadi and esophageal pressure (Peso) were recorded during unstressed and stressed spontaneous
breathing and under assisted ventilation delivered in pressure support (PS) at low and high assist
level and in neurally adjusted ventilatory assist (NAVA). Peak, mean and integral of Eadi,
breathing pattern, esophageal pressure-time product (PTPeso) and work of breathing (WOB)
were calculated offline.
Results: Median [interquartile range] peak Eadi at baseline was 17 [13-22] μV and was above
10 μV in 92% of the cases. Eadi max defined as Eadi measured at maximal inspiratory capacity
reached 90 [63 to 99] μV. Median peak Eadi/Eadi max ratio was 16.8 [15.6-27.9] %. Compared
to baseline, respiratory rate and minute ventilation were decreased during stressed non assisted
breathing whereas peak Eadi and PTPeso were increased. During unstressed assisted breathing,
peak Eadi decreased during high level PS compared to unstressed non-assisted breathing and
to NAVA (p = 0.047). During stressed breathing, peak Eadi was lower during all assisted
ventilation modalities compared to stressed non-assisted breathing. During assisted ventilation,
across the different conditions, peak Eadi changed significantly whereas PTPeso and
WOB/minute were not significantly modified. Finally, Eadi signal was still present even when
Peso signal was suppressed due to high assist levels.
Conclusion: Eadi analysis provides complementary information compared to respiratory pattern
and to Peso monitoring, particularly in presence of high assist levels.
Keywords: Respiratory drive, Spontaneous breathing, Electrical activity of the diaphragm,
Pressure support ventilation
18
Deciphering the genetic etiology of pediatric cancers through an integrative gene network
approach
Savary Clara1, Kim Artem1, Lespagnol Alexandra2, Gandemer Virginie2, Pellier Isabelle3,
Andrieu Charlotte4, Pagès Gilles5, Galibert Marie-Dominique1, Blum Yuna6, De Tayrac Marie1
1Institut de Génétique et Développement de Rennes – IGDR, 2CHU Pontchaillou, 3CHU
Angers, 4INSERM U1242-COSS, 5Centre Scientifique de Monaco – CSM, 6Cartes d'Identité
des Tumeurs (CIT) - Ligue Contre le Cancer
The genetic etiology of childhood cancers still remains largely unknown. It is therefore essential
to develop novel strategies to unravel the spectrum of pediatric cancer genes. Statistical network
modeling techniques have emerged as powerful methodologies for enabling the inference of
gene-disease relationship and have been performed on adult but not pediatric cancers. We
performed a deep multi-layer understanding of pan-cancer transcriptomic data selected from
the Treehouse Childhood Cancer Initiative through a co-expression network analysis. We
identified six modules strongly associated with pediatric tumor histotypes that were
functionally linked to developmental processes. Topological analyses highlighted that pediatric
cancer predisposition genes and potential therapeutic targets were central regulators of cancer-
histotype specific modules. A module was related to multiple pediatric malignancies with
functions involved in DNA repair and cell cycle regulation. This canonical oncogenic module
gathered most of the childhood cancer predisposition genes and clinically actionable genes. In
pediatric acute leukemias, the driver genes were co-expressed in a module related to epigenetic
and post-transcriptional processes, underlying the critical role of these pathways in the
progression of hematologic malignancies. This integrative pan-cancer study provides a
thorough characterization of the key regulators of pediatric tumor-associated modules and
enables investigating the genes involved in childhood tumorigenesis.
Keywords: gene network, systems biology, pediatric cancers, genetic etiology, pan-cancer
analysis, gene expression
19
Ketogenic diet benefits against Mycobacterium ulcerans infection: keys toward wound
management improvement in Buruli ulcer
Foulon Mélanie1, Robbe-Saule Marie1, Esnault Lucille1, Kempf Marie2, Marion Estelle1,
Marsollier Laurent1
1INSERM, 2CHU d’Angers
Introduction: Ketogenic diet is used for several years in a wide range of pathologies (epilepsy,
cancer…). Some studies demonstrated the advantages of this diet in wound healing and tissue
repair while some others showed utility of this diet in treatment of bacterial infections (urinary
tract infections) and/or inflammatory diseases (gout, acnes…).Taken together, these studies
bring out the idea that ketogenic diet may be useful to help an organism to take over an
inflammation and/or an infection. However, few studies have pushed the investigations
supporting this idea. Buruli ulcer, or Mycobacterium ulcerans infection, is a chronic infectious
disease characterized by large skin ulcerations and a severe local inflammation. In this context,
we evaluated the impact of a ketogenic diet on this pathology using an in vitro murine model
mimicking each stage of human M. ulcerans infection.
Material and methods: Two mice groups (n=25), under conventional (control) or ketogenic diet
respectively were infected by M. ulcerans (104 bacilli/tail). The evolution of lesion
development was followed and histological and microbiological analyses were performed.
Results: Our primary observations showed that the kinetic of the lesions development was
drastically delayed comparatively to mice under a conventional diet. To understand this feature,
we were interested in characterization of both host and M. ulcerans responses. We first
highlighted a decrease of the local skin inflammation in mice under ketogenic diet. Moreover,
results showed that bacterial burden was significantly lower in theses tissues. In vitro
experiments showed that M. ulcerans growth was slower in a ketogenic environment context.
Conclusion: In summary, our results show that ketogenic diet provides consequent benefits to
the host in face of the M. ulcerans infection in mice. We seek now to take advantage of these
benefits and associated it to usual antibiotic treatments in order to reduce treatment length and
improve wound healing in Buruli ulcer, a current major objective according to the World Health
Organization (WHO).
Keywords: Inflammation, Mycobacteria, Skin lesions
20
Maternal Malnutrition and Hypothalamic Development
Frapin Morgane1, Meistermann Dimitri2, Guignard Simon1, Paillé Vincent1, Parnet Patricia1,
Amarger Valérie1
1INRA - UMR 1280, 2INSERM – UMR 1064
Maternal malnutrition during pregnancy can impact neural development of the child and thus
alter cognitive performance and food intake regulation in short- and long-term. All neural cells
(except microglia) arise from the same neural stem cells. Stem cells fate and differentiation are
determined by extrinsic factors, including maternal and fetal hormones secreted by the
peripheral organs, such as insulin, leptin and IGFs, and an intrinsic gene expression program
involving transcription factors and epigenetic marks. We are using a well-characterized
maternal protein restriction model in rat. An impaired control of feeding behaviour and
alterations of the neural circuits of the hypothalamus were evidenced in this model. By a
combination of cellular and molecular approaches, we aimed at determining the impact of
maternal diet during pregnancy on proliferation and differentiation capacities of neural stem
cells in the hypothalamus. The proportion of the different cell types in hypothalamus at the end
of gestation was determined by immunostaining with specific markers. In parallel,
hypothalamic cell transcriptome of fetuses, new-born and adult rats was analysed by DGE-seq.
This analysis pointed out that the expression of several key genes involved in
neurodevelopment, mitochondrial metabolism and synaptogenesis was impacted. Moreover,
essential genes for the setting-up and the reading of m6A epitranscriptomics marks were
affected by maternal protein restriction. These marks control mRNA stability, translation and
degradation and seem to be involved in neurodevelopment. Detection by fluorescence analysis
have shown that the level of m6A marks is globally lower in the restricted group compared to
control group. These preliminary results suggest the fact that epitranscriptomic may underlie
the short- and long-term effects of maternal nutrition during pregnancy. Our next step will be
the characterization of our model more precisely at the epitranscriptomic and molecular levels,
specifically targeting stem cell differentiation regulation pathways.
Keywords: Hypothalamus, Maternal Nutrition, Epitranscriptomic
21
Generation of homogenous monovalent and trivalent glycoconjugate vaccines against
Streptoccocus pneumoniae using unnatural amino acid incorporation
Violo Typhaine1, Allot Adrien1, Dussouy Christophe1, Tellier Charles1, Grandjean Cyrille1,
Camberlein Emilie1
1UFIP
Streptoccocus pneumoniae is a bacteria responsible for serious diseases such as pneumonia or
meningitis and leads to the death of approximately one million of children each year. Efficient
anti-pneumococcal glycoconjugate vaccines made of bacterial capsular polysaccharides have
been launched. However, these vaccines confer protection to seven or thirteen out of the
approximately 90 pneumoccocus serotypes identified so far. Therefore finding an efficient
vaccine against all of them is still a challenge. Moreover, the current conjugation techniques
used to prepare the glycoconjugate vaccines do not allow to finely controlling the amount and
position of conjugated carbohydrate haptens, a feature which strongly impacts the fate of the
immune response. In this context, we plan to generate a vaccine that consists in a conjugate of
a well-conserved surface protein of S. Pneumoniae (PsaA), for the targeting of a wider range
of serotypes, with a capsular tetrasaccharide (“Gal-Glc-(Gal-)GlcNAc”) that induces effective
immunity against one of the most common serotype of S. Pneumoniae (serotype 14).To finely
control the site of the capsule tetrasaccharide conjugation on the protein we used the
incorporation of propargyl-Lysine, an unnatural amino acid (UAA), during the translation of
PsaA. The introduced propargyl-Lysine brings the click chemistry function necessary to
perform homogenous and site-specific glycoconjugation with the synthetic tetrasaccharide
equipped with a bioorthogonal azide-functionalized spacer. Using this technology we have
produced homogenous monovalent and trivalent glycoconjugates that will be used for mice
immunization.
Keywords: Glycoconjugate, Unnatural amino acids, vaccine
22
Development of a new murine model for Enterococcus faecium intestinal colonization
S. Reissier1, V. Bordeau1, B. Felden1, V. Cattoir1,2,3, M. Revest1,4
1Unité Inserm U1230, Université Rennes 1, Rennes, France, 2CHU de Rennes, Service de
bactériologie-hygiène hospitalière, Rennes, France, 3CNR de la Résistance aux Antibiotiques
(laboratoire associé 'Entérocoques'), Rennes, France, 4CHU de Rennes, Service de Maladies
Infectieuses, Rennes, France.
Introduction: Enterococcus faecium is a ubiquitous organism usually present in normal human
gut microbiota and natural environment, which can cause diverse infections including urinary
and intrabdominal infections as well as bacteremia and infective endocarditis. E. faecium is
commonly responsible for healthcare-associated infections and hospital outbreaks.
Understanding colonization mechanisms seems to be essential to manage those infections and
to limit hospital spread. Several experimental models of intestinal colonization have been
described using different antibiotic protocols. The aim of this study was to develop a novel
model of intestinal colonization as close as possible to human conditions.
Methods: Protocols were performed using 6-week specific-pathogen-free Swiss mice. Mice
were treated with antibiotics to decolonize the intestinal tract, and then a calibrated suspension
(108 CFU/mL) of vancomycin-resistant E. faecium was orally inoculated. The vanB-positive
Aus0004 reference strain recovered from a bacteremic patient was used. A fecal pellet was
collected for each mouse before inoculation and at D3, D5, D7, D10 and D14 after colonization.
Pellets were homogenate in saline and viable bacterial counts were determined by serially
diluting the homogenates and plating the diluted specimens onto Trypticase Soy agar and Bile
Esculine Azid agar. Five antibiotics protocols were tested, clindamycin associated with
gentamicin; ceftriaxone associated with cefoxitin; ceftriaxone alone; ceftriaxone associated
with amoxicillin and cefoxitin; and ceftriaxone associated with amoxicillin. A group received
no antibiotic as negative control.
Results: Five mice were randomized in each group. No E. faecium intestinal colonization was
observed in the control group. At D3, fecal pellets contained on average 4.109 CFU of E.
faecium per gram with all antibiotics protocols. With clindamycin-gentamicin association, we
observed a decrease of about one log10 CFU/g every two days from D3. With the other four
antibiotic regimens, the bacterial load obtained at D3 was maintained and stable until D14. A
concomitant colonization by Enterococcus faecalis was observed in groups treated with
ceftriaxone alone and ceftriaxone-cefoxitin combination.
Discussion: Five antibiotic combinations were tested to develop a murine model to study E.
faecium intestinal colonization. Clindamycin-gentamicin combination did not provide stable
colonization for 14 days. A significant and stable colonization was obtained with antibiotic
associations without amoxicillin, but a concomitant colonization by E. faecalis was observed.
Both ceftriaxone-amoxicillin-cefoxitin and ceftriaxone-amoxicillin combinations provided
significant and stable E. faecium colonization without co-colonisation by E. faecalis. To be as
close as possible to human situation, ceftriaxone-amoxicillin seemed to be the most appropriate
for E. faecium intestinal colonization model.
Keywords: Microbiology, experimental model, intestinal colonization, Enterococcus faecium
23
Transposition from a batch to continuous formulation process of pentamidine-loaded
nanopolyplexes to treat Leishmaniasis
Matha Kevin1, Benoit Jean-Pierre1, Gimel Jean-Christophe1, Gangneux Jean-Pierre2,
Calvignac Brice1
1Micro et Nanomedecines Translationnelles, MINT, Univ Angers, INSERM 1066, CNRS 6021,
Université Bretagne Loire, 2Université de Rennes, Inserm, EHESP, Irset UMR S1085
This work aims at transposing the manufacturing of biodegradable and biocompatible
nanopolyplexes (NP) from a batch to a continuous process. The NP were composed of
hyaluronic acid and polyarginine and were loaded with an antiparasitic agent namely
pentamidine.
Methods:Pentamidine-loaded NP were developed at a laboratory batch scale and physico-
chemically characterized in terms of size, polydispersity index, zeta potential, morphology,
sterility and osmolality. The freeze-drying process was optimized to improve the stability of
the formulation. Then the pentamidine-loaded NP were transposed and scaled up according to
a continuous process. The in vitro activity of the encapsulated drug was assessed and compared
with the standard injectable form of pentamidine (Pentacarinat) and compared with another
nanomedicine used in clinics namely the liposomal form of amphotericin B(AmBisome). In
vitro assays were performed with a model of THP-1 cells infected with
Leishmania guyanensis.
Results:Pentamidine-loaded NP were prepared using the ionotropic gelation technique. The NP
size was about 180 nm, with a low polydispersity index (PdI< 0.15), and a negative zeta
potential (-25mV). Following freeze-drying and resuspension in water, the NP maintained
theirinitial physico-chemical characteristics showing an encapsulation efficiency of about 70
%. The formulation process yielded a sterile, injectable product with an osmolality compatible
with an intraveinous injection. Knowing the feasibility of the batch formulation, a successful
transposition using a micromixer was performed. The formulation showed a low toxicity on
THP-1 cells and efficacy towards a leishmanial model.
Conclusions: Here we reported the development and characterization of stable pentamidine-
loaded NP.The physical and chemical characteristics (size, polydispersity, zeta potential,
entrapment effciency, pH, osmolality) of the obtained formulation were compatible with an
intraveinous injection. This work showed that the batch process was easily transposable to a
continuous process paving the way for a future scale up in Good Laboratory and Manufacturing
Practices (GLP/GMP) compliance. This is done by the means of a dedicated microfluidic pilot
under development in our laboratory. This pilot allows nanomedicines production in aseptic
conditions.
Keywords: Polyplexes, Leishmania, Pentamidine, Microfluidics
24
Development and application of a non-targeted approach to characterise human exposure
to halogenated chemicals of concern in human breast milk
Mariane Pourchet1, Ronan Cariou1, Emmanuelle Bichon1, Bruno Le Bizec1, Jean-Philippe
Antignac1
1LABERCA, UMR 1329 Oniris-INRA, Nantes, France
Since centuries, human are exposed to chemicals present everywhere in our environment (food,
water, air, dust, etc.). This wide range of contaminants still increases and interferes with the
environmental-food-human continuum. In order to keep an eye on this constant evolution and
to act as early warning support to policy, the Human Biomonitoring for European Union project
(HBM4EU, EU H2020)-workpackage 16 “emerging chemicals” aims to establish a workflow
able to produce a general overview of chemicals exposure. This is based on large screening
methods, suspect/non-targeted screening (NTS), which are new valuable strategies aiming to
detect unknown markers of exposure without any a priori and still at early stage of development
in the human biomonitoring field.
The non-targeted approach, in combination with latest and future generations chromatography
coupled to high resolution mass spectrometry (LC and GC-HRMS), opens the door to holistic
characterisation of biological samples. In order to make this work of large screening feasible,
we refocused our research on halogenated contaminants which are already known as persistent,
toxic and bio-accumulative. The lipophilic character of those compounds supposes to expect
them in lipophilic tissue and/or in storage or excretion compartments, such as adipose tissue,
breast milk, placenta, meconium.
In this context and in order to partly characterise the early stage of life exposure, we developed
an appropriate suspect/non-targeted screening workflow able to detect a large range of
compounds, including chemicals of emerging concern (CEC), in human breast milk. Non-
targeted sample preparation and instrumental method were optimised. The data processing was
focused on halogenated compounds thanks to isotopic pattern and mass defect of chlorinated
and brominated molecules by developing HaloSeeker application (Léon et al., 2019). Based on
this suspect/non-targeted methodology and as a first proof of concept a pesticide’s metabolite,
the 4-hydroxy-chlorothalonil, was identified in breast milk with LC-HESI-HRMS (Q-Orbitrap)
analysis. The present work describes challenges, recent promising results and future
expectations of this method.
Léon A, Cariou R, Hutinet S, Hurel J, Guitton Y, Tixier C, Munschy C, Antignac J-P, Dervilly-
Pinel G, Le Bizec B. HaloSeeker 1.0, a user-friendly software to highlight halogenated
chemicals in non-targeted high resolution mass spectrometry dataset. Analytical Chemistry
2019,91:3500−3507
Keywords: Human biomonitoring, Non-targeted screening, Chemicals of emerging concern,
Liquid and gas phase chromatography coupled to high resolution mass spectrometry (LC and
GC-HRMS)
25
Exposure of the Lebanese population to aluminum and analysis of food determinants.
El Daouk Sarine1,2, Pineau Alain1, Al Iskandarani Mohamad2, Hijazi Akram2
1Nantes University - IICiMED – ERATU, 2Lebanese University
Background: Aluminum (Al) consumption in Lebanon is in perpetual growth, the metal is
widely used in various applications specifically in industrial products and food market therefore
human body is subjected to its exposure. This study aims to pilot the consumption of food
containing Al from the Lebanese market and to quantify the level of metal in different dietary
matrices in order to study the major contributors to its exposure among the Lebanese
population.
Methods: A cross sectional study was conducted using a customized self-reported semi
quantitative Electronic - Food Frequency Questionnaire (e-FFQ) developed subsequent to EPIC
(European Prospective Investigation into Cancer & Nutrition) study model and based on
Lebanon Food Based Dietary Guideline (FBDG) portion size. Curve® platform was created
and used to collect participant’s answers, data collection followed a Mobile-Web-Analytical
software process. The e-FFQ link targeted 20.000 individuals living across the Lebanese
regions distributed proportionally, aged between 18 and 64 years old. Selection of food was
based upon the results of French EAT2 study. Al level in food was analyzed using Flame -
Atomic Absorption Spectrometry (FAAS). Data was analyzed using SPSS version 25.
Results: 167 respondents have filled the e-FFQ. 98 food items were studied in 2018, Al levels
had a mean of 3.56 ± 2.08 ranging from (0.14 to 9.37) and the highest levels were found in
vegetables followed by sauces and condiments, candies and ready meals. PTWI (Provisional
Tolerable Weekly Intake) of Al was estimated to 0.55 mg/Kg bw (60 Kg/person). Al Daily
Dietary Exposure was estimated to 4726.45 mg/day, with the highest food exposure for lettuce,
soft drinks, ice cream and tea.
Conclusion: This study provides an estimate of the Lebanese adult population dietary intake of
Al, after analyzing data from a semi quantitative metal based e-FFQ and analyzing food samples
by AAS. The estimated intake determined for this population does not exceed the established
thresholds of tolerable intake.
Keywords: Aluminum, Food Matrix, e-FFQ, PTWI, Daily dietary exposure, FAAS
26
New generation of glioblastoma-targeted lipid nanocapsule hydrogel: a sustained and
specific drug delivery system
Gazaille Claire1, Farooq Umer1, Mellinger Adélie1, Eyer Joel1, Bastiat Guillaume1
1Micro et Nanomedecines Translationnelles, MINT, UNIV Angers, UMR INSERM 1066,
UMR CNRS 6021, Angers, France
The standard of care of glioblastoma (GBM), malignant brain tumours, consists in a tumor
resection, followed by the Stupp protocol (chemotherapy and / or radiotherapy) 4 to 6 weeks
later. Compared to the surgical procedure alone, this non-curative and non-specific protocol
allowed a slight increase in the median survival, from 12 to 14 months, but without preventing
tumor recurrence, leading to the death of the patients. One of the factors associated with
recurrence is the gap between surgery and the Stupp protocol, but necessary for good tissue
healing and recovery of the patient. The objective of this project is to develop an implantable
therapeutical hydrogel which will bridge this gap to ensure continuity in treatment for patients
with GBM. A hydrogel of self-associated lipid nanocapsules (LNCs), without a polymer matrix,
was obtained in collaboration with Catholic University of Louvain, and allowed the gradual
release of gemcitabine-loaded LNCs. Promising results have shown the therapeutic efficacy in
vivo of this implant in murine GBM resection models.1–3 However, the released LNCs were
not specific to GBM cells. The aim of this project is to design an active targeting strategy using
the hydrogel of LNCs. One of the possibilities is the use of NFL-TBS.40-63 (NFL) peptide,
able to associate with LNCs in suspension and to allow their vectorization in vivo after
intratumoral injection.4–6 In this project, different types of LNC hydrogels were formulated in
the presence of the NFL peptide. The free NFL proportion, without prior separation, was
quantified using a size exclusion chromatography (using an UPLC system) technique. The NFL
peptide had a higher affinity (instantaneous total adsorption) for negatively charged LNCs than
the neutral ones. The rheological properties of the NFL-loaded hydrogel were close to the non-
loaded one. The NFL peptide remained totally adsorbed at LNC surface after the hydrogel
dissolution. In addition, in vitro studies on three GBM cell lines showed a faster internalization
of NFL-loaded LNCs than the non-loaded ones. Finally, when LNCs were loaded with
gemcitabine, their cytotoxicity increased with the NFL adsorbed at their surface, proving a
better specificity. In the near future, gemcitabine/NFL-loaded hydrogels will be evaluated in
vivo on the murine GBM resection model already developed and the best ones will be tested in
combination with temozolomide, chemotherapy
used in Human GBM treatment.
1. Bastiancich, C. et al. Lauroyl-gemcitabine-loaded lipid nanocapsule hydrogel for the
treatment of glioblastoma. J. Controlled Release 225, 283–293 (2016). 2. Bastiancich, C. et al.
Injectable nanomedicine hydrogel for local chemotherapy of glioblastoma after surgical
resection. J. Controlled Release 264, 45–54 (2017). 3. Bastiancich, C. et al. Evaluation of
lauroyl-gemcitabine-loaded hydrogel efficacy in glioblastoma rat models. Nanomed. 13, 1999–
2013 (2018). 4. Balzeau, J. et al. The effect of functionalizing lipid nanocapsules with NFL-
TBS.40-63 peptide on their uptake by glioblastoma cells. Biomaterials 34, 3381–3389 (2013).
5. Karim, R. et al. Enhanced and preferential internalization of lipid nanocapsules into human
glioblastoma cells: effect of a surface-functionalizing NFL peptide. Nanoscale 10, 13485–
13501 (2018). 6. Carradori, D., Saulnier, P., Préat, V., des Rieux, A. & Eyer, J. NFL-lipid
nanocapsules for brain neural stem cell targeting in vitro and in vivo. J. Controlled Release 238,
253–262 (2016).
Keywords: Lipid nanocapsule hydrogel, Specific targeting, Glioblastom
27
Tribbles Homolog 1 is a negative regulator of FOXP3 in regulatory T cells
Feseha Yodit1, Judor Jean-Paul1, Conchon Sophie1, Brouard Sophie1, Danger Richard1
1Universite De Nantes
Objective: Tribbles Homolog 1 (TRIB1) kinase-like protein is known to be associated with
several human diseases. This includes immune-mediated inflammatory bowel diseases and
chronic rejection from renal transplanted patients in which regulatory T cells (Tregs) has a
significant contribution. Thus far, TRIB1 is known to be among the genes upregulated in Tregs
in comparison to conventional CD4+ T cells. Also, TRIB1 was previously identified as a
protein-binding partner of FOXP3, a master regulator of Tregs. However, the precise role and
molecular action of TRIB1 in Treg cells remain to be elucidated.
Methods: To investigate the role of TRIB1 in Treg; Treg-specific (Foxp3eYFP-Cre)Trib1
knock-out (Trib1 KO) were generated and compared with Trib1 wildtype littermates (control).
Flow cytometry analyser and cell sorter were used for immune phenotyping and cell sorting of
ex-vivo experiments, respectively. Also, the effect of TRIB1 over-expression was studied in
Human Treg (CD4+CD25highCD127-) cells using GFP expressing lentiviral constructs.
Results: Trib1 KO mice of 8 weeks old displayed splenomegaly with a 10-times increase of
total splenocyte numbers. Splenocyte immune cells phenotyping using cytometry showed an
increased percentage of CD44+CD62Llo cells, indicating an accumulation of effector/memory
T cells in Trib1 KO mice. In vitro, Trib1 deletion resulted in Treg induction impairment and
dysfunctional Treg proliferation. Also, TRIB1 over-expression in Human Treg cells induced an
impaired Treg expansion followed with a decreased proliferation rate. We also evidenced
TRIB1 expression level is regulated downstream of T cell signalling in Treg cells.
Conclusion: Altogether, these results evidenced that stable TRIB1 expression is needed for
appropriate Treg induction and cell proliferation. These findings are amidst the growing interest
in the Tribbles protein family in immune cells. Also, increasing our understanding of genes
such as TRIB1 in Tregs will contribute to the advancement of improved therapies in immune-
related diseases.
Keywords: Regulatory T cells, Immunology, Autoimmune Diseases, CD4 T cells, FOXP3
28
Genetic and molecular basis of the phenotypic and functional structuration of the NK cell
repertoire: implication in the context of acute leukaemia
Dhon Roméo Makanga1,2,5, Gaëlle David1,2,5, Francesca Da Rin de Lorenzo1,2,5, Catherine
Willem1,2,5, Léa Dubreuil1,2,5, Nolwenn Legrand1,2,5, Thierry Guillaume2,3, Pierre Peterlin3,
Marie C Béné2,4,5, Alice Garnier3, Patrice Chevallier2,3,5, Anne Cesbron1, Katia Gagne1,2,5,
Béatrice Clemenceau2,5, Christelle Retière1,2,5.
1Etablissement Français du Sang, Nantes, France, 2CRCINA, INSERM, CNRS, Université
d’Angers, Université de Nantes, Nantes, France, 3Hematology Clinic, CHU, Nantes, France,
4Hematology Biology, CHU, Nantes, France, 5LabEx IGO “Immunotherapy, Graft, Oncology”,
Nantes, F-44000, France
NK cells are key cytotoxic effectors against leukemias. KIR and HLA genes participate to the
structural and functional formation of NK cell repertoire. Cytomegalovirus (CMV) modifies
this repertoire favoring educated NK cell expansion. Moreover, the expression of numerous NK
receptors increases the phenotypic and functional diversity of NK cell repertoire. Thus, a broad
inter individual diversity exists in the structure and function of NK cell repertoire. In this study,
we deeply investigated the antileukemic potential of NK cells against a panel of acute myeloid
(AML) and lymphoid (ALL) cell lines and primary leukemic cells, taking into account the KIR
and HLA genetic parameters, NK cell development stages and CMV status of blood donors
(n=68). The main NK cell subsets were identified by flow cytometry on the basis of CD57,
KIR2DL3, NKG2A and NKG2C differentiating markers. The NK cell repertoire analysis of
each donor group, determined by Genesis® software, highlights a strong impact of KIR and
HLA genetic and CMV status. Thus, B+ KIR genotypes favor higher frequency of
NKG2A+KIR+ NK cell subset, A3/A11 environment favors higher mature CD57+ and
CD57+KIR+ NK cell frequencies and Bw4 favors NKG2A+ and NKG2A+CD57+ NK cell
frequencies. As expected KIR+CD57+NKG2C+ NK cell frequency was significantly higher in
CMV+ individuals. On the functional side, we observed that lymphoid cell targets were better
recognized by NK cells than myeloid cell targets. However, a broad disparity of NK cell
responses exists against a same leukemic target highlighting bad and good responders. In
addition, the best responders against one leukemic target were not systematically good
responders against other target cells suggesting that the NK cell responses were dependent of
the nature of leukemic cells. We showed that CMV- KIR2DS1- individuals were the best
responders to ALL H9. The most effective NK cell subsets against ALL targets were NKG2A+.
In contrast, C1C2 AA KIR genotyped individuals mediated the best responses against AML
KG1. Mature CD57+ NK cell subsets were the most effective NK cell subsets against KG1. In
accordance with previous report, KIR+ NK cells were the best efficient NK cell subsets against
primary AML. Overall, our data may have evident clinical implications as they can optimize
the selection of Hematopoietic Stem Cell (HSC) donors on immunogenetic bases and identify
the best NK cell subsets in immunotherapy in accordance to the leukemia nature.
Keywords: KIR, HLA, NK cells repertoire, acute leukemia
29
Pro-inflammatory stimuli increase ICAM-1 expression in enteric glial cells and favor T
cell adhesion
Pabois Julie1, Durand Tony1, Le Berre Catherine1, Neunlist Michel1, Neveu Isabelle1,
Naveilhan Philipe1
1Inserm 1235
Objectives: Enteric plexitis are defined as an abnormal accumulation of immune cells such as
T lymphocytes, in and around enteric nervous ganglia. In Crohn’s disease, the presence of
myenteric plexitis in the proximal margin of ileocolonic resection represents one of major
predictive factor of post-operative recurrence. To understand the mechanisms leading to the
formation of myenteric plexitis, the interactions between enteric glial cells (EGC) and T
lymphocytes were studied in vitro under pro-inflammatory conditions.
Methods: To analyze the impact of pro-inflammatory environment on EGC/T cell interactions,
co-cultures were developed. EGC were isolated from rat's colonic myenteric plexus whereas T
cells were obtained from the spleen or mesenteric ganglia. EGC were pre-incubated (24h) with
LPS or TNFα/IL1-β prior to their co-culture for two hours with T cells activated or not by anti-
CD3/anti-CD28 antibodies. After the removal of non-adherent T cells, fixed cells were staining
and the number of T cells (CD4+, CD8+) interacting with EGC (S100β+) was counted. The
expression of adhesion molecules in ECG was examined by Q-PCR and immunocytochemistry.
Results: T cell activation increased the number of T cells-EGC contact. Pre-treatment of EGC
with pro-inflammatory stimuli (LPS or TNFα/IL1-β) also increased the number of naïve or
activated T lymphocytes interacting with EGC. Analyzes of T cell subsets revealed that pro-
inflammatory conditions favored the interactions of both CD4+ and CD8+ T lymphocytes with
EGC. Moreover, stimulation of EGC with LPS or TNFα/IL1-β induced an overexpression of
the cell surface molecule ICAM-1 in EGC.
Conclusion: Our present results demonstrate that T lymphocytes interact directly with EGC.
Under pro-inflammatory conditions, the positive regulation of ICAM-1 in EGC is correlated
with a higher number of T cells interacting with EGC. Further experimentations are required to
determine the exact role of ICAM-1 and its ligand LFA-1 in the establishment of this neuro-
immune cellular contact.
Keywords: Plexitis, Crohn's disease, Enteric glial cell, T cell, Inflammation
30
Molecular responses involving in mitochondrial biogenesis depend on the training type in
the trout red muscle
Pengam Morgane1, Moisan Christine1, Simon Bernard1, Amérand Aline1
1Université de Bretagne Occidentale
Training exercise is recognized to improve human health and its beneficial effects are in part
related to enhancement of muscle mitochondrial performance. Nevertheless, the involved
cellular and molecular mechanisms are not still fully elucidated. Currently, one of the
challenges is to determine the best training exercise protocols which optimize signaling
pathways involved in mitochondrial biogenesis and antioxidant defenses, such as AMPK–PGC-
1α, which largely participate to the health benefit effects. The main purpose of the present study
was to compare the effects of MICT (Moderate Intensity Continuous Training) and HIIT (High
Intensity Interval Training) on these metabolic pathways in the skeletal muscle of rainbow trout.
In this study, six different training protocols were developed. Trained rainbow trouts were
compared to untrained fishes. All these protocols are characterized by a duration (10 or 20
days), an intensity (moderate or high), a frequency (continuous or interval) and a volume (low
or high). The training volume takes all parameters into account and it is determined with this
calculation: Training volume = duration x frequency x intensity. We determined mRNA levels
(AMPK, PGC-1α, citrate synthase, oxidative phosphorylation complexes, UCPs and
antioxidant enzymes) and enzymatic activities (citrate synthase and antioxidant enzymes) in
skeletal muscle. Plasmatic isoprostane levels were dosed. Training of high intensity and low
volume (corresponding to HIIT) stimulates more rapidly and more intensely than a training of
moderate intensity and high volume (corresponding to MICT) the transcripts levels and the
enzymatic activities in the trout skeletal muscle, mainly in the red oxidative muscle. As in
mammals, our results suggest that HIIT is more effective than MICT to stimulate molecular
compounds involving in mitochondrial biogenesis and oxidative capacities. Thus, HIIT could
promote benefits on health in fish.
Keywords: Exercise trainings, Skeletal muscle, Mitochondrial biogenesis, Antioxydant
defenses
31
Feces-derived extracellular vesicles from patients with liver diseases cause barrier
dysfunctions by reducing ZO-1 and occludin expressions via non-muscular light chain
kinase-dependent pathway
Alexandre Villard1,2, Nadia Benabbou1, Mireille Wertheimer1, Jérôme Boursier2 &
Ramaroson Andriantsitohaina1
1INSERM U1063, Stress Oxydant et Pathologies Métaboliques, Université d'Angers, Angers,
France, 2Laboratoire HIFIH, UPRES 3859, Université d'Angers, Angers, France
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and its
prevalence is estimated to 25% of the world population. NAFLD can progress to liver
inflammation stage called non-alcoholic steatohepatitis (NASH) which will lead in the worst
cases to cirrhosis and even hepatic cancer. These liver diseases are influenced by many factors
and notably gut microbiota alterations, known as dysbiosis. Alterations of bacterial
communities participate to barrier dysfunctions and hence liver inflammation. Gut microbiota-
derived extracellular vesicles (EVs) have been shown to participate in the development of
insulin resistance in a mice model of obesity. No evidences about the possible implication of
gut microbiota-derived EVs in barrier dysfunctions have been provided in the course of liver
diseases. The objective of the present study is to characterize EVs of feces from NAFLD and
NASH patients who undergo liver biopsy. Secondly, EV effects on barrier functions of
intestinal epithelial, endothelial and hepatic cells are analyzed, in Caco-2, human aortic
endothelial cells (HAoEcs)) and hepatocytes (HepG2), respectively. We isolate two populations
of EVs depending on the centrifugation speed used (17K and 150K) similar in size and
concentration but greater protein content in EVs 150K compared to EVs 17K. Interestingly, the
two populations of EVs are composed of Gram-positive and Gram-negative EVs as well as EVs
from eukaryote origin including epithelial cells. EVs from both NAFLD and NASH patients
reduce trans-epithelial electric resistance of Caco-2 and increase the number of bile canaliculi
of HepG2. These effects are associated with reduced expression of tight junction proteins,
zonula occludens-1 (ZO-1) and occludin, in both types of cells. In Caco-2 cells, the non-myosin
light chain kinase (nMLCK) inhibitor ML-7 prevents the ability of NAFLD and NASH EVs to
increase permeability and to decrease ZO-1 expression. In contrast, stimulation by NASH EVs,
but not NAFLD EVs, increases permeability of HAoECs and this is associated with a greater
number of transmigrated monocytes across the endothelial cells. Altogether, we provide
evidence of the presence of two populations of EVs in feces from liver disease patients; these
EVs are from prokaryote and eukaryote sources. The two types of EVs affect differently barrier
dysfunctions. Whereas EVs from NAFLD and NASH patients participate actively in the
destabilization of the intestinal and hepatic barrier, EVs from NASH patients, but not from
NAFLD patients, affect endothelial barrier. The mechanism involves alteration of tight junction
proteins via an nMLCK-dependent pathway in epithelial cells. Thus, feces-derived EVs can be
considered as new players in the evolution of liver diseases.
Keywords: Extracellular Vesicles, Microbiota, Barriers, Hepatic diseases
32
Polycyclic aromatic hydrocarbons trigger a hepatocyte release of pro-apoptotic
extracellular vesicles
Nettie van Meteren1, Dimitri Gobart1, Isabelle Gallais1, Eric Le Ferrec1, Dominique Lagadic-
Gossmann1 et Odile Sergent1
1Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail)
- UMR_S 1085, F-35000 Rennes, France
Background: PAHs, environmental pollutants resulting from incomplete combustion of organic
materials, are considered for some of them as hepatotoxicants. They can be found in cigarette
smoke and contaminated food, the main exposure route for non-smokers. Extracellular vesicles
(EVs) are major actors of intercellular communication, described as mediators in several
pathogenic processes including liver diseases. Regarding xenobiotic-induced liver injury, EVs
appear to have a role in drug-induced liver injury (DILI); yet no information is available on EV
implication in toxicant-associated liver diseases such as TAFLD (Toxicant-Associated Fatty
Liver Disease) and TASH (Toxicant-Associated SteatoHepatitis). We previously demonstrated
that three PAHs i.e benzo(a)pyrene (BP), dibenzo(a,h)anthracene (DBA) or pyrene (PYR), were
able not only to increase EV release by primary rat and WIF-B9 hepatocytes, but also to modify
EV composition. Therefore, the aim of this work was to study the impact of those hepatocyte-
derived EVs on other hepatocytes thus considered as target hepatocytes.
Material & Methods: WIF-B9 and primary rat hepatocytes were treated by 100 nM BP, DBA
or PYR for 72 hours and 18 hours, respectively. The three PAHs were selected based upon their
various concentrations in food and affinities for aryl hydrocarbon receptor (AhR), the
transcription factor mediating most of the biological effects of several PAHs. Then, EVs were
isolated from extracellular medium by differential ultracentrifugation and untreated hepatocytes
were exposed to 5 μg/mL EVs during 24 hours.
Results: EVs released from PAH-treated hepatocytes (PAH-EVs) were more cytotoxic than
control EVs, as they triggered an increase in apoptosis of target hepatocytes and activation of
caspases. This apoptosis was demonstrated to be dependent on an EV uptake by endocytosis.
In line with this, PAH-EVs were able to reach the lysosomal compartment which was
implicated in PAH-EV- induced cell death. Moreover, after PAH-EVs treatment, a lysosome
membrane permeabilization (LMP) was found and lysosome pH was increased. As the
expressions of the NADPH oxidase subunits and of the iron storage protein, ferritin, were higher
in PAH-EVs, it could be suggested that Fenton and Haber-Weiss iron-dependent reaction
occurred in lysosomes leading to the production of the powerful oxidative species, hydroxyl
radical. Thus, using iron chelators, PAH-EVs-induced cell death was attenuated. Finally, PAH-
EVs were capable of generating an oxidative stress in target hepatocytes mainly localised in the
lysosomal compartment.
Conclusion: PAH-EVs are implicated in apoptosis of target hepatocytes suggesting a possible
involvement of extracellular vesicles in PAH-induced liver injury.
Keywords: Extracellular vesicles, Apoptosis, Polycyclic aromatic hydrocarbons, Hepatocytes
33
Poster
34
Poster sessions:
• #1: Tuesday 10 December, 10h30-11h15
• #2: Tuesday 10 December, 15h00-15h45
• #3: Wednesday 11 December, 11h00-11h30
• #4: Wednesday 11 December, 15h30-16h15
Title Authors Poster
session
N°
Poster
Characteristics of
Pruritus in Relation to
Self-assessed Severity
of Atopic Dermatitis
Flavien Huet, Laurent Misery and Christelle
Ianotto 1
1
Crystalline silica
impairs the
efferocytosis ability of
human and mouse
macrophages
Alain Lescoat, Alice Ballerie, Marie Lelong,
Stéphane Jouneau, Patrick Jégo, Olivier
Fardel, Laurent Vernhet and Valérie Lecureur
1 2
STIM1 at the plasma
membrane is implicated
in B cell migration?
Nelig Le Goux and Olivier Mignen 1 3
Circulating extracellular
vesicles from metabolic
syndrome patients
induce insulin
resistance in adipocytes
Ali Sakina, Vergori Luisa, Le Lay Soazig,
Simard Gilles, Dubois Séverine,
Andriantsitohaina Ramaroson and Martinez
M. Carmen
1 4
Role of the extracellular
chaperone clusterin in
myocardial infarction
Louwana Allawa, Sophie Tamareille, Justine
Beaumont, Simon Blanchard, Celine
Beauvillain, Pascale Pignon, Antoine Poirier,
Yves Delneste, Thomas Bochaton, Michel
Ovize, Pascale Jeannin and Fabrice Prunier
1 5
Social and intentional
use of facial
expressions in red-
capped mangabeys
(Cercocebus torquatus)
Juliette Aychet, Catherine Blois-Heulin,
Elisabetta Palagi and Alban Lemasson 1 8
The role of
ADAMTS12 in the
progression of the
hepatocellular
carcinoma
Fida Azar, Bassil Dekky, Christine Monseur,
Dominique Bonnier, Alain Colige, Vincent
Legagneux and Nathalie Theret
1 9
Burrowing functional
and immunogenetic
information through the
1000 Genomes Project
with Ferret v.3.0
Rokhaya Ba, Sophie Limou, Nicolas Vince,
Estelle Geffard, Dorian Malguid, Marie Lanza
and Pierre-Antoine Gourraud
1 10
35
Temporal models of
care sequences for the
exploration of medico-
administrative data
Johanne Bakalara, Thomas Guyet, Emmanuel
Oger, Olivier Dameron and André Happe 1 11
Etude de glycoclusters
anti-adhésion contre
Pseudomonas
aeruginosa au cours de
la mucoviscidose
Marvin Bauduin, Geneviève Hery-Arnaud,
Eric Kipnis and Rodrigue Dessein 1 12
Mutations of SF3B1
disrupt its own splicing
and produce a novel
SF3B1 isoform in
myelodysplastic
syndromes with ring
sideroblasts.
Tiffany Bergot, Eric Lippert, Nathalie Douet-
Guilbert, Laurent Corcos and Delphine
Bernard
1 16
The white matter
structural support of the
ventral attention
network
Florian Bernard, Philippe Menei and Aram
Ter Minassian 1 17
The inflammasome of
tumor cells in colorectal
cancer: a potential
target to strengthen the
Th1/Tc1 response of
tumor infiltrating T
lymphocytes (TILs)
Linda Bilonda Mutala, Delphine Dansette,
Cécile Deleine, Romain Oger, Nicolas Jouand,
Juliette Podevin, Pierre Fourquier, Emilie
Thibaudeau, Jérôme Chetritt, Jean-François
Mosnier, Céline Bossard, Nadine Gervois,
Camille Brochier and Anne Jarry
1 18
An in vitro and in silico
validation study for PC
MRI and derived bio-
markers
Marco Castagna, Jean-Michel Serfaty and
David Le Touzé 1 22
New Phosphorylation
Sites of Rad51 by c-
Met Modulate
Presynaptic Filament
Stability
Thomas Chabot, Alain Defontaine, Damien
Marquis, Axelle Renodon-Corniere,
Emmanuelle Courtois, Yvonnick Cheraud and
Fabrice Fleury
1 23
Effects of seven weeks
of spirulina
supplementation on
physical performances
and biological markers
in elite rugbymen
players
Mehdi Chaouachi 1 24
Behavioural and
neurobiological impact
of prenatal maternal
stress in Japanese quail
(Coturnix coturnix
japonica)
Marion Charrier, Marion Georgelin, Maryse
Meurisse, Paul Constantin, Flore Lormant,
Céline Nicolle, Aline Bertin, Sophie
Lumineau, Ludovic Calandreau and Cécilia
Houdelier
1 25
36
Development and initial
validation of a
questionnaire for self-
assessment of
supportive and
palliative needs in
patients with cancer
François Chaumier, Marianne Bourdon and
Jean-Benoît Hardouin 1 27
Altered mitochondrial
dynamics induced
endothelial cell
dysfunction and
increased
atherosclerosis in the
mouse
Ahmad Chehaitly, Anne-Laure Guihot, Linda
Grimaud and Daniel Henrion 1 28
Identification of CFTR
cis-regulatory variants
Mégane Collobert, Karen Rouault, Carine
L'Hostis, Marie-Pierre Audrézet, Claude Férec
and Stéphanie Moisan
1 29
Distinct types of
biocide activity against
Gram-positive
pathogens
Loren Dejoies, Brice Felden and Vincent
Cattoir 1 34
Development of small
molecules preventing
Homologous
Recombination in
cancer cells
Alexandre Demeyer, Fabrice Fleury, Pierre
Weigel and Monique Mathe-Allainmat 1 35
Acceptance and
rejection of care among
hospitalized children
Anaïs Deshayes 1 36
Benchmarking Protein
Structure Prediction
Strategy using a
Pentatpeptide based
Structural Alphabet
(SA) type
Surbhi Dhingra, Bernard Offmann, Frederic
Cadet and Sowdhamini Ramanathan 1 37
A computational
framework to simulate
bioprinted cells and
extracellular matrix
mechanobiochemical
interactions
Arthur Douillet, Fabien Guillemot and Pascal
Ballet 1 40
Aqueous two-phase
systems : physico-
chemical
characterization by
phase diagram design
Florence Dumas, Emilie Roger, Lazhar
Benyahia and Jean-Pierre Benoit 1 41
A novel strategy to
identify melanoma-
Emilie Dupré, Agnès Fortun, Floriane Briand,
Nathalie Labarrière, Amir Khammari,
Catherine Rabu and François Lang
1 42
37
antigen from long non
coding RNA
Mitochondrial lipid
changes and oxidative
stress in non-alcoholic
fatty liver disease
progression
Manon Durand, Marine Coue, Mikael Croyal,
Thomas Moyon, Angela Tesse, Florian Atger,
Khadija Ouguerram and David Jacobi
1 43
A multi-omic approach
reveals how microbiota-
hypothalamus axis
adapts to a Western-diet
short-term exposure in
rats.
Mélanie Fouesnard, Johanna Zoppi, Mélanie
Petera, Carole Migne, Fabienne Devime,
Stéphanie Durand, Alexandre Benani, Samuel
Chaffron, Véronique Douard and Gaëlle
Boudry
1 47
Easy-HLA: prediction
and compatibility level
assessment available in
a complete webtool
suite
Estelle Geffard, Léo Boussamet, Alexandre
Walencik, Sophie Limou, Nicolas Vince and
Pierre Antoine Gourraud
1 48
Neutrophil-derived
extracellular vesicles
induce endothelial
inflammation and
damage through the
transfer of miRNAs
Alexandre Glemain, Mélanie Néel, Rozenn Le
Bloas, Sarah Bruneau and Fadi Fakhouri 1 49
Le suivi quantitatif de
l’ADN tumoral
circulant est prédictif de
la réponse du mélanome
cutané métastatique à
l’immunothérapie anti-
PD1
Guillaume Herbreteau, Audrey Vallée, Anne-
Chantal Knol, Sandrine Théoleyre, Gaëlle
Quéreux-Baumgartner, Emilie Varey, Amir
Khammari, Brigitte Dréno and Marc Denis
1 50
The study of DNA
damage and recovery in
HL60 cell line after
treatment with taxanes
Iman Amrani, Houda Benhelli-Mokrani,
Ghania Belaaloui and Fabrice Fleury 2 5
ING2 plays a major role
in the DNA Damage
Response by promoting
repair through classical
NHEJ
Jérôme Archambeau, Audrey Mouche, Laura
Chaillot, Charles Ricordel and Rémy Pedeux 2 6
Identification of a new
regulator of
mitochondrial DNA
copy number
Jade Aurriere, Majida Charif, David
Goudenège, Rodolphe Perrot, Arnaud
Chevrollier, Guy Lenaers and Salim Khiati
2 7
Computer-assisted
transcatheter aortic
valve-in-valve
implantations
Réda Belhaj Soulami, Miguel Castro, Jean-
Philippe Verhoye and Pascal Haigron 2 13
38
Accuracy of P0.1
measurements
performed by ICU
ventilators: a bench
study.
Francois Beloncle, Lise Piquilloud and Alain
Mercat 2 14
Design of a
Comanipulated robot
for prostate
bracytherapy
Aziza Ben Halima, Julien Bert and Dimitris
Visvikis 2 15
Role of PPARβ/δ in
human MSC response
to inflammatory stimuli
Benoit Bodic 2 19
IFNα and IL21 promote
distinct populations of
effector B cells
Marina Boudigou, Nedra Chriti, Alexis
Grasseau, Jacques-Olivier Pers, Sophie
Hillion and Laëtitia Le Pottier
2 20
V/Q SPECT for the
assessment of regional
lung function:
generation of normal
mean and standard
deviation 3-D maps.
David Bourhis, Philippe Robin, Pierre Yves
Salaun and Pierre Yves Le Roux 2 21
Effect of iron on the
development of oral
biofilm.
Kanchana Chathoth, Fabrice Mahé, Bénédicte
Martin, Martine Bonnaure-Mallet, Olivier
Loreal, Stéven Yvenou and Christine Baysse
2 26
Development of
primary immune cell
tracking with a new-
generation of
multimodal far-red
emitting polymer probe.
Malo Daniel, Jean-Paul Judor, Sophie
Brouard, Sophie Conchon, Laurence Dubreil,
Marie-Thérèse Charreyre and Arnaud Favier
2 30
Biomarkers and novel
therapeutic approaches
targeting metabolism
reprogramming in
hepatocellular
carcinoma
Yoann Daniel, Anne Corlu and Florian
Cabillic 2 31
Prescribing trends of
AEDs from 2011 to
2017 among pregnant
women treated with
sodium valproate:
nationwide
observational study
from the French
National Health
Insurance Database.
Adeline Degremont, Elisabeth Polard,
Sandrine Kerbrat, Caroline Rault, Annie-
Pierre Jonville-Béra, Virginie Ringa, David
Travers, Emmanuel Oger and Arnaud Biraben
2 32
Understanding the role
of SIRPg in Immunity Safa Dehmani 2 33
39
Endothelium as a new
target in HFpEF?
Justine Dhot, Mélanie Burban, Valentine Prat,
David Stevant, Marine Ferron, Antoine
Persello, Virginie Aillerie, Angélique Erraud,
Angela Tesse, Michel De Waard, Bertrand
Rozec, Jean-Noël Trochu, Chantal Gauthier
and Benjamin Lauzier
2 38
Volume variation may
be a relevant metric in
the study of aneurysm
pulsatility: a study
using ECG- gated 4D-
CTA (PULSAN)
Brieg Dissaux, Julien Ognard, Mourad
Cheddad El Aouni and Jean-Christophe
Gentric
2 39
Assessing Health-
Related Quality of Life
(HRQoL) in patients
before and after kidney
transplantation:
exploring measurement
invariance using
network analysis.
Line Auneau-Enjalbert, Jean-Benoit
Hardouin, Myriam Blanchin, Magali Giral,
Aurélie Meurette and Véronique Sébille
2 44
Tricellular junctions: a
deep insight and cross
talk with bicellular
junction
Thomas Esmangart de Bournonville and
Roland Le Borgne 2 45
Gait analysis to
evaluate patients with
moderate haemophilia:
a research protocol
Alban Fouasson-Chailloux, Marc Trossaert,
Claire Vinatier, François Rannou, Marc
Dauty, Jérôme Guicheux and Yves Maugars
2 46
Evidence of the
respiratory
magnetometer
plethysmography for
the estimation of minute
ventilation during low
to moderate intensities
Aya Houssein, Di Ge, Steven Gastinger,
Remy Dumond and Jacques Prioux 2 51
Impact of KIR and
HLA genotypes on
rituximab-mediated
antibody-dependent
cellular cytotoxicity
(ADCC) responses of
the KIR+ NK cell
subsets
Dhon Roméo Makanga, Nolwenn Legrand,
Gaëlle David, Catherine Willem, Anne
Cesbron, Katia Gagne, Béatrice Clemenceau
and Christelle Retière
2 52
First trimester serum
biomarkers in
pregnancies
complicated with
placental chronic
inflammation
Claire de Moreuil, Marie-Pierre Moineau,
Maël Padelli, Françoise Lede, Annabelle
Remoue, Christophe Tremouilhac, Philippe
Merviel, Brigitte Pan Petesch, Emmanuelle Le
Moigne, Karine Lacut, Pascale Marcorelles
2 53
40
Mesenchymal stromal
cells’ secretome can
activate
osteoclastogenesis and
block multinucleated
giant cells formation in
vitro
Paul Humbert, Meadhbh A. Brennan, Julien
De Lima, Frédéric Blanchard and Pierre
Layrolle
2 54
Novel therapeutic
strategies that interfere
senescence escape for
the treatment of
resistance in colorectal
and breast cancer.
Raneem Jatal, Olivier Coqueret, Eric Lelievre
and Maria de La Fuente
2 55
Development and
characterization of a
Roux-en-Y Gastric
Bypass model in obese
Yucatan minipigs: A
pilot study.
Damien Bergeat, Sophie Blat, Yentl Gautier,
Sylvie Guérin, Isabelle Le Huërou-Luron,
Ronan Thibault and David Val-Laillet
3 56
Evaluation of the
effectiveness of the
eradication of
Enterobacteriaceae
OXA-48 from the
murine digestive tract
by phagotherapy
François Javaudin, Eric Batard and Emmanuel
Montassier 3 57
Clinical validity of a
new method using
wearable monitors to
assess ambulatory pain-
free and maximal
walking times in
peripheral artery
disease
Pierre Jehannin, Ségolène Chaudru,
Guillaume Mahe and Alexis Le Faucheur 3 58
Recombinant AAV-
mediated gene transfer
to the skeletal muscle is
associated to immune
modulation of transgene
expression in the
macaque model
Malo Journou 3 59
Characterization of
genes involved in the
pathogenicity of
Scedosporium
apiospermum
Samar Kabbara and Nicolas Papon 3 60
Modèle de mini-porcs
du Yucatan dénutris :
composition corporelle,
phénotypage
Laurence Lacaze, Steve Touboulic, Julien
Georges, Francis Le Gouevec, Alain Chauvin,
Ronan Thibault and David Val-Laillet
3 62
41
moléculaire et analyse
du microbiote
Impact of physician
expertise on probe
trajectory during
obstetric ultrasound: a
quantitative approach
for skill assessment.
Maela Le Lous, Fabien Despinoy, Pierre
Jannin and Vincent Lavoue 3 66
Revisiting the
regulatory mechanism
of tetracycline
resistance tet(M) gene
expression
Killian Le Neindre, Vincent Cattoir and Brice
Felden 3 67
Investigating the role of
TET1 in modulating
chromatin architecture
Audrey Lejart, Catherine Chapuis, Agnès
Burel, Aurélien Dupont, Sébastien Huet and
Gilles Salbert
3 71
Increased anti-tumor
efficacy of PD-1
deficient melanoma-
specific human
Lymphocytes
Marotte Lucine, Simon Sylvain, Vignard
Virginie, Dupre Emilie, Gantier Malika,
Cruard Jonathan, Alberge Jean Baptiste,
Hussong Melanie A., Deleine Cecile, Heslan
Jean-Marie, Shaffer Jonathan M., Gaschet
Joëlle, Scotet Emmanuel, Fradin Delphine,
Marotte Lucine, Tuan Nguyen, Beauvais
Tiffany and Labarriere Nathalie
3 72
Automatic recognition
of retinal pathologies in
a context of massive
screening using deep
learning
Sarah Christina Matta 3 73
Distribution study of
paracetamol and its
metabolites in rat whole
body after on-tissue
chemical derivatization
by MALDI Mass
Spectrometry Imaging
Mira Merdas, Antoine Lhumeau, Quentin
Vanbellingen, Melanie Lagarrigue, Thierry
Umbdenstock, Geroges Da Violante and
Charles Pineau
3 74
Transfer of ingested
short-chain chlorinated
paraffins to laying hen
tissues (gallus gallus
domesticus)
Marie Meziere, Ronan Cariou, Philippe
Marchand, Elisabeth Baeza-Campone, Céleste
Le Bourhis, Gaud Dervilly and Bruno Le
Bizec
3 75
Isolation and
identification of
xylophagous fungi
hosted by bark beetles
from Aleppo pine
forests in eastern
Algeria
Lyès Moumeni, Mustapha Bounechada,
Farida Benia, Louiza Gillmann, Wilfried
Poirier, Sandrine Giraud, Jean-Philippe
Bouchara and Amandine Gastebois
3 79
42
Upper extremity
musculoskeletal
disorders: how many
cases are potentially
preventable? Estimates
from the Cosali cohort
for the French region of
Pays de la Loire
Aboubakari Nambiema, Julie Bodin, Natacha
Fouquet, Sandrine Bertrais, Agnes Aublet-
Cuvelier, Susan Stock, Bradley Evanoff,
Alexis Descatha and Yves Roquelaure
3 80
3D reconstruction of the
knee bone surface using
markerless 3D
ultrasound
Maged Nasan, Yannick Morvan and
Guillaume Dardenne
3 81
Activation of Nav
channels with the
neurotoxin, veratridine
induces vasorelaxation
mediated by NO-
pathway of murine
mesenteric arteries
Joohee Park, Claire Legendre, Coralyne
Proux, Daniel Henrion and Christian Legros 3 85
Impact of a-
Radioimmunotherapy
on tumor
microenvironment
Justine Perrin, Marisa Capitao, Sebastien
Gouard, Catherine Maurel, Cedric Louvet,
Mélanie Lancien, Frank Bruchertseifer, Alfred
Morgenstern, Michel Cherel, Joëlle Gaschet
and Yannick Guilloux
3 86
Effects of apigenin in
endocrine-resistant
breast cancer
Thu Ha Pham, Yann Le Page, Gilles Flouriot
and Farzad Pakdel 3 87
Lignin degradation
pathway in
Scedosporium species
Wilfried Poirier, Jean-Philippe Bouchara and
Sandrine Giraud 3 88
The association of
extracellular vesicles
and microcarriers as an
innovative approach in
regenerative medicine
Melody Riaud 3 93
Inhibitor of growth two
(ING2) is involved in
mitochondrial
homeostasis
Charles Ricordel, Marie Tiercin, Nicolas
Bigot, Audrey Mouche, Agnès Burel, Benoit
Desrues and Remy Pedeux
3 94
Characterization of
FasL cleavage by
metalloproteases
Vesna Risso and Matthieu Le Gallo 3 95
Protective role of the
mitochondrial fusion
protein Opa1 in
hypertension:
Mitochondrial aspect
Pauline Robert, Phuc Minh Chau Nguyen,
Arnaud Chevrollier, Linda Grimaud, Guys
Lenaers, Daniel Henrion and Laurent Loufrani
3 96
43
B cells committed to
the plasma cell
différenciation need to
downregulate the
IL4/pSTAT6/CD23
pathway
Kathleen Santamaria, Alexia Saintamand and
Thierry Fest 3 101
Slam practice: review
of cases reported to the
addictovigilance of
Pays de La Loire
Benoit Schreck, Caroline Victorri Vigneau
and Marie Grall Bronnec 3 102
Une supplémentation
maternelle postnatale en
fenugrec augmente la
production de lait dans
un modèle de rate
allaitant 12 ratons
Thomas Sevrin, Clair-Yves Boquien and
Marie-Cécile Alexandre-Gouabau 3 103
A yeast based high-
throughput screening
assay to target protein-
protein interactions.
Aswani Sudevan and Gwenaël Rabut 3 104
Effects of GTP-
analogues on
microtubule structure
studied by cryo-electron
microscopy
Siou Ku, Laurence Duchesne and Denis
Chrétien 4 61
Intra tumoral immune
and stromal
heterogeneity in
follicular lymphoma: an
implication in relapses
and responses to
immunotherapies?
Claire Lamaison, Marine Seffals and Frederic
Mourcin 4 63
Scatter estimation in
PET imaging using
Deep Learning U-Net
architecture
Baptiste Laurent, Thibaut Merlin, Alexandre
Bousse, Didier Benoit and Dimitris Visvikis
4 64
A New small RNA
involved in the
regulation of
staphylococcal
virulence
Kim Boi Le Huyen, Cintia D. Gonzalez,
Philippe Bouloc, Svetlana Chabelskaya and
Brice Felden
4 65
Cyclin-Dependant
Kinases(CDK) inhibitor
effects on brain edema,
blood brain barrier
permeability and glial
inflammation on focal
model of rat ischemia.
Lucas Le Roy and Serge Timsit 4 68
44
Enteric nervous system
remodeling in a rat
model of spinal cord
injury on T8
Chloe Lefevre, Philippe Aubert and Michel
Neunlist 4 69
Investigation of
mutations and
epimutations in
chlordecone-exposed
children from
guadeloupean
TIMOUN cohort
Louis Legoff, Christine Monfort, Sébastien
Auber, Marion Josse, Shereen D'Cruz, Luc
Multigner and Fatima Smagulova
4 70
Effects of high fat diets
on metabolic
parameters and markers
of colonic permeability
in dogs
Alex Moinard, John Flanagan, Agnès André,
Khadija Ouguerram, Patrick Nguyen and
Véronique Leray
4 76
Exploring T cell - B cell
collaboration in
Multiple Sclerosis
through B cell
differentiation analysis
Jérémy Morille, Stéphane Rodriguez, Amé-
Thomas Patricia, Tarte Karin, Alexandra
Garcia, Laureline Berthelot, Arnaud Nicot,
Sophie Brouard, David-Axel Laplaud and
Laure Michel
4 77
The effect of soluble
guanylase cyclase &
beta3-adrenoceptor
activation on the
circulatory function of
the watanabe heritable
hyperlipidemic rabbit
Michelle Moughaizel, Yassine Mallem,
Chantal Thorin and Jean-Claude Desfontis 4 78
Characterization of BK-
specific monoclonal
antibodies in kidney
transplant recipients
after BK reactivation
Ngoc Khanh Nguyen, Laetitia Gautreau-
Rolland, Marie-Claire Devilder, C. Fourgeux,
J. Poschmann, Audrey Rodallec, M.
Hourmant, Céline Bressollette-Bodin, Xavier
Saulquin and Dorian McIlroy
4 82
Prevalence and
characteristic of
multisite
musculoskeletal
symptoms among
district hospital nurses
in Haiphong, Vietnam
Thanh Hai Nguyen, Julie Bodin, Jean-
Dominique Dewitte and Yves Roquelaure 4 83
Non Invasive Prenatal
Diagnosis of Single
Gene Disorders using
long read technologies
Mathilde Pacault, Claude Férec and Magali
Champion 4 84
Full characterization of
hepatitis B viral forms
from patient plasma
according to HBeAg
status and genotype
using velocity gradient
Charlotte Pronier, Jérémy Bomo, Valentine
Genet, Philippe Gripon and Vincent Thibault 4 89
45
Prognostic value of
somatic focal
amplifications on
chromosome 30 in
canine oral melanoma:
interest for comparative
oncology
Prouteau, Chocteau, de Brito, Cadieu, Primot,
Botherel, Degorce, Cornevin, Lagadic,
Cabillic, de Fornel, Devauchelle, Derrien,
Abadie, André and Hédan
4 90
Restoration of miR-16
tumor suppressor
activity in uveal
melanoma
Anais Quemener, Laura Bachelot, Marie
Dominique Galibert and David Gilot 4 91
Comparison of tri-
culture and co-culture
cells models in
investigating the
toxicity of a
phycotoxin, okadaic
acid, on the intestinal
barrier
Océane Reale 4 92
CETOREIN: Effect of
ketogenic diet on
metastatic renal
carcinoma. A pilot
study.
Cyrielle Rolley, Nathalie Baize, Jeremy
Richard, Vincent Procaccio and Pierre Bigot 4 97
Exposition au
Chlordécone et risque
d'anomalies
congénitales, à partir de
la cohorte mère-enfant
TIMOUN en
Guadeloupe
Florence Rouget, Philippe Kadhel, Christine
Monfort, Jean-François Viel, Jean-Pierre
Thome, Sylvaine Cordier and Luc Multigner
4 98
Nanoparticles based on
poly(benzyl malate)
derivatives: evaluation
of their uptake by
human macrophages
and hepatoma cells
Saad Saba, Elise Vène, Catherine Ribault,
Nicolas Lepareur, Sandrine Cammas-Marion
and Pascal Loyer
4 99
Mitochondria transfer
from tumor-activated
stromal cells (TASCs)
to primary
Glioblastoma cells.
Céline Salaud, Alvarez-Arenas, Geraldo,
Belmonte-Beita, Calvo, Gratas, Pecqueur,
Garnier, Vallette and Oliver
4 100
KDM6B an epigenetic
regulator of lymphoid
stroma ?
Marvin Sylvestre, Vonick Sibut, Céline
Monvoisin, Karin Tarte and David Roulois 4 105
CADBIOM - A
software for the
identification of
controllers in signalling
and control networks
Pierre Vignet, Nathalie Théret and Anne
Siegel 4 106
46
extracted from large
scale standardized
networks
Repurposing of
Auranofin and
Honokiol as antifungal
agents against the
therapy-refractory
Scedosporium species
complex and
Lomentospora
prolificans
Hajar Yaakoub and Maxime Fleury 4 107
Mise au point et
caractérisation d’un
modèle de sepsis
polymmicrobien murin
par injection
intrapéritonéale de
matières fécales
Alexandre Mansour, Blandine Dizier, Nicolas
Nesseler, Johanne Delannoy, Pascale
Gaussem and Christilla Bachelot-Loza
4 108
47
List of participants
Nom Prénom Organisation City of the
organisation
ALI Sakina U1063 Stress oxydant et pathologies
métaboliques
Angers
ALLAWA Louwana MITOVASC Angers
AMRANI Iman UFIP Nantes
ARCHAMBEAU Jérôme U1242 - Chemistry Oncogenesis Stress Signaling
(COSS)
Rennes
AURRIERE Jade MitoVasc - UMR Inserm 1080 Angers
AYCHET Juliette EthoS (UMR 6552) Rennes
AZAR Fida IRSET U1085 Rennes
BA Rokhaya CRTI UMR 1064 Nantes
BAKALARA Johanne EA-REPERES 7449 Rennes
BAUDUIN Marvin U1078 - Axe microbiota Brest
BELHAJ SOULAMI Réda LTSI Rennes
BELONCLE François Mitovasc Angers
BEN ABID Amal LTSI Rennes
BEN HAIMA Aziza LaTim (laboratoire de traitement de de
l'information médicale)
Brest
BERDAL Marion U1232 Nantes
BERGEAT Damien NuMeCan Rennes et St Gilles
BERGOT Tiffany UMR 1078 "génétique, génomique fonctionnelle
et biotechnologies"
Brest
BERNARD Florian CRCINA Angers
BEVANT Kevin U1241 Numecan Rennes
BILONDA MUTALA Linda CRCINA INSERM U1232 Nantes
BODIC Benoit INSERM U1229 RMeS Nantes
BOUDIGOU Marina U1227 - LBAI Brest
BOURHIS David GETBO Brest
CASTAGNA Marco Institut du Thorax - Université Nantes Nantes
CHABOT Thomas UFIP UMR 6286 Nantes
CHAOUACHI Mehdi Mouvement, Sport, Santé (M2S) Rennes
CHARRIER Marion UMR 6552 - Laboratoire d'éthologie animale et
humaine
Rennes
CHATHOTH Kanchana NUMECAN Rennes
CHAUMIER François UMR INSERM 1246 SPHERE Nantes
CHEHAITLY Ahmad MitoVasc Angers
COGNEZ Noriane IRSET Rennes
COLLOBERT Mégane Génétique, Génomique Fonctionnelle et
Biotechnologies
Brest
CONAN Maël IRSET Rennes
DANIEL Malo CRTI UMR 1064 Nantes
DANIEL Yoann U1241 NuMeCan Rennes
DEGREMONT Adeline EA 7449 - REPERES Rennes
DEHMANI Safa INSERM UMR 1064 (CRTI) Nantes
48
DEJOIES Loren Inserm U1230 ARN régulateurs bactériens et
médecine
Rennes
DEMEYER Alexandre UFIP UMR CNRS 6286 Nantes
DE MOREUIL Claire EA 38 78 GETBO Brest
DESHAYES Anaïs Centre Atlantique de Philosophie Nantes
DHINGRA Surbhi UFIP Nantes
DHOT Justine L'institut du thorax Nantes
DISSAUX Brieg GETBO Brest
DOUILLET Arthur LaTIM UMR 1101 Brest
DUMAS Florence MINT INSERM 1066 / CNRS 6021 Angers
DUPLOUYE Pierre CRTI UMR1064 Nantes
DUPRÉ Emilie CRCINA Nantes
DURAND Manon Institut du thorax Nantes
EL DAOUK Sarine IICiMed -Cibles et Médicaments des Infections et
du Cancer
Nantes
AUNEAU-
ENJALBERT
Line UMR INSERM 1246 SPHERE Nantes
ESMANGART DE
BOURNONVILLE
Thomas IGDR UMR 6290 Rennes
FESEHA Yodit CRTI UMR1064 Nantes
FOUASSON-
CHAILLOUX
Alban RMeS Nantes
FOUESNARD Mélanie NuMeCan Rennes
FOULON Mélanie CRCINA U1232 Angers
FRAPIN Morgane UMR 1280 PHAN Nantes
GAZAILLE Claire MINT Angers
GEFFARD Estelle INSERM 1064 Nantes
GHANEM Rosy U1078 Brest
GLEMAIN Alexandre ITUN/CRTI - INSERM UMR1064 Nantes
HERBRETEAU Guillaume UMR 1232 (CRCINA) équipe 2 Nantes
HOUSSEIN Aya Laboratoire Mouvement Sport Santé Bruz
HUET Flavien LIEN Brest
HUMBERT Paul U1238 Phy-OS Nantes
JATAL Raneem CRCINA INSERM U1232, equipe 12 Angers
JAVAUDIN François MiHAR lab Nantes
JEHANNIN Pierre CIC 1414 INSERM Équipe micro et
macrocirulation
Rennes
JOURNOU Malo UMR1089 Nantes
KABBARA Samar GEIHP Angers
KU Siou UMR CNRS 6290 Rennes
LACAZE Laurence NUMECAN Rennes
LAMAISON Claire inserm 1236 Rennes
LAURENT Baptiste LaTIM Brest
LE DARÉ Brendan NuMeCan Rennes
LE GOUX Nelig U1227 LBAI Brest
LE HUYEN Kim Boi INSERM U1230 Rennes
LE LOUS Maela MédiCis Rennes
LE NEINDRE Killian INSERM U1230 Rennes
LE ROY Lucas Inserm 1078 Brest
49
LEFEVRE Chloe inserm TENS u1235 Nantes
LEGOFF Louis IRSET - U1085 Rennes
LEJART Audrey Institut de Génétique et Développement de
Rennes
Rennes
LELOU Elise U1241 NuMeCan Rennes
LESNE Laurianne Irset Inserm U1085 Rennes
MAAROUF Amine INSERM U1232 equipe 12 Angers
MAKANGA Dhon
Roméo
Laboratoire recherche EFS, Equipe 1 UMR1232,
CRCINA CRCINA
Nantes
MANSOUR Alexandre CIC-P 1414 Rennes Rennes
MARAGE Louis Inserm U-1099, LTSI - METRIQ Rennes
MARCHAND Tony INSERM U1236 / Frenette Lab Rennes / New York
MAROTTE Lucine INSERM U 1232 Nantes
MATHA Kevin MINT INSERM 1066/CNRS 6021 Angers
MATTA Sarah LaTIM Brest
MERDAS Mira Protim, Irset, Inserm U1085 Rennes
MEZIERE Marie LABERCA, UMR 1329 Oniris-INRA Nantes
MOINARD Alex NP3, Oniris Nantes
MORILLE Jérémy UMR1064 Nantes
MOUGHAIZEL Michelle NP3, Oniris Nantes
MOUMENI Lyès GEIHP Angers
NAMBIEMA Aboubakari Irset - Inserm U1085 - Equipe Ester Angers
NASAN Maged LaTIM - INSERM U1101 Brest
NGUYEN Ngoc
Khanh
CRTI UMR 1064 Nantes
NGUYEN Thanh Hai Inserm UMR 1085 - Equipe Ester Angers
OUZAID Idir IRSET Equipe 8 Rennes
PABOIS Julie Inserm UMR 1235 - TENS Nantes
PACAULT Mathilde Inserm U1078 Brest
PARK Joohee Laboratoire MitoVasc Angers
PENGAM Morgane EA 4324 (ORPHY) Brest
PERRIN Justine U1232 Nantes
PETIT Coralie U1232 Team 12 Angers
PHAM Thu Ha Irset - Inserm UMR_S 1085 Rennes
PIQUILLOUD
IMBODEN
Lise Laboratoire Mitovasc Angers
POIRIER Wilfried GEIHP Angers
POURCHET Mariane LABERCA, UMR 1329 Oniris-INRA Nantes
PRONIER Charlotte irset Rennes
PROUTEAU Anaïs IGDR, UMR6290 Rennes
PRUVOST-
COUVREUR
Manon LABERCA, UMR 1329 Oniris-INRA Nantes
QUÉMÉNER Anaïs IGDR Rennes
REALE Océane ANSES Fougères
REISSIER Sophie Inserm U1230 Rennes
RIAUD Melody U1063 SOPAM & U1232 CRCINA Angers
RICORDEL Charles INSERM U1242 COSS Rennes
RISSO Vesna UMR1242 Rennes
ROBERT Pauline Mitovasc Angers
50
ROLLEY Cyrielle MitoVasc Angers
ROUGET Florence INSERM-IRSET U1085 Rennes
SABA Saad NuMeCan Rennes
SALAUD Céline inserm 1232 Nantes
SANTAMARIA Kathleen U1236 MICMAC Rennes
SAVARY Clara Institut de Génétique et Développement de
Rennes - IGDR
Rennes
SCHRECK Benoît UMR 1246 SPHERE Nantes
SEPEHRI Shima LaTIM Brest
SEVRIN Thomas Physiopathologie des adaptations nutritionelles Nantes
SUDEVAN Aswani Institut de Génétique et Développement de
Rennes (IGDR)
Rennes
SYLVESTRE Marvin U1236 Rennes
TABAJA Zainab institut de recherche en immunologie et
cancérologie Nantes/Angers
Nantes
TOMASI Jacques Laboratoire Traitement du Signal et de l’Image
(LTSI)
Rennes
VAN METEREN Nettie IRSET Rennes
VIGNET Pierre UMR-INSERM1085 Rennes
VILLARD Alexandre U1063 SOPAM Angers
VIOLO Typhaine UFIP Nantes
YAAKOUB Hajar GEIHP Angers
51
Practical information
L’hostellerie du Bon Pasteur : 18 Rue Marie-Euphrasie Pelletier, 49100 Angers,
Tél : 0 (33) 02 41 72 12 80
By car: a parking lot is accessible by the hotel.
From the train station: 20 min by walking, 5-10 min by taxi, 10 min by bus : Line 4
(Beaucouze-l’Atoll), Bon Pasteur stop
From downtown: 30 min by walking, 5-10 min by taxi, 6-10 min by bus : Line 4 and 6, Bon
Pasteur stop
Tuesday evening social event:
Wallaby’s Australian Café: 60 Boulevard du Maréchal Foch, 49100 Angers