Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome...

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Transcript of Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome...

Page 1: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

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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

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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

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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

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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

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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

Page 11: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

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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

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“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

Page 14: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

Page 15: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

Page 16: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

Page 17: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

Page 18: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

Page 19: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

Page 20: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

Page 21: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

Page 22: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

Page 23: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

Page 24: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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)

Page 25: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

Page 26: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

Page 27: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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

Page 28: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

Page 29: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

Page 30: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

Page 31: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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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

Page 32: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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

Page 33: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

33

Poster

Page 34: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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

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

Page 35: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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

Page 36: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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

Page 37: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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

Page 38: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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

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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

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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

Page 41: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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

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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

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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

Page 44: Summary - Ecole Doctorale Biologie Santé (BS)...3 Tuesday, December 10, 2019 8h30-9h30 Welcome reception, distribution of bags and badges 9h30-9h45 Opening plenary: Laurent Beck,

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

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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

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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

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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

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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

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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

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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

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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