Common ARRIMAGE resources
Fundings
We will ask for funding to the three University hospital Centres to ensure the permanent animation of the FHU and to finance every year emerging projects in the form of internal calls for young investigators and to finance the preparation of large projects such as RHU and EU grant applications. Particular emphasis will be placed on international attractiveness, by promoting the recruitment of young talents (eg ERC, ATIP avenir). The FHU ARRIMAGE program for the forthcoming 4 years relies on existing national and international funding of grants related to the project for a total of 6.75 M€; 6 teams of the FHU are involved in the OMAGE project financed by the Fond Regional de Cooperation pour la Recherche (FRCR) of the Region Grand-EST (total: 2.1 M€), which represent a major part of the FHU new program. The positioning of the FHU relies on international projects that include ANR/CONACYT NuTTTMED grant, EU Healthy diet-Healthy life grant DIFAMEM and ERA-NET DrNanoDAll (total 3.8 M€). The FHU is also involved in the I-Site “Lorraine Université d’Excellence” (LUE), in GEENAGE and Biomolecules programs (total 550 k€). A PHRCi “SEPT9_SuRV” has been granted for studying biomarkers of the transition from NASH/cirrhosis to hepatocarcinoma (WP2) (300k€).
Cohorts
The FHU program relies on national and international cohorts hosted in FHU (ALDEPI-OBESPI (France), DANTOKPA (Benin), EDEN (France), OASI (Italy)) and international networks of cohorts (David Meyre, UL and Mc Master).
– EOS-ALDEPI (Extreme Obesity treated by Surgery) cohort (PI L Brunaud) follows 400 patients prospectively recruited in CHRU of Nancy for bariatric surgery. Experimental design: evaluation of nutritional and metabolic status, preoperative comorbidities, clinical imaging and biological phenotyping. Biological samples include DNA, serum, adipose tissue (mesenteric, subcutaneous, grand omentum), liver biopsies, intestinal juice and urines. Post-operative follow-up is performed every 6 months with serum collection. Samples are stored in CRB-Inserm. Related documents: Signed informed consents. Ethical approval from Research Ethics Committee and declaration to CNIL.
– The OASI cohort (joint collaboration of OASI medical institute in EpiAGE European consortium, co PI JL Guéant) has been designed to evaluate the association of gene-gene and gene-environment interactions with the risk for metabolic disorders in Sicily. The 1500 volunteers (65-85 y) were recruited door to door. Investigations included medical history, life style, environmental exposure, nutritional intake, vascular function, anthropometry, collection of PBMC, blood and urine samples. Diseased obesity was frequent, with BMI 25-30: 39.5%, superior to 30: 33.3% and metabolic syndrome, 30.0 %. DXA densitometric analyses were carried out on 20% of the cohort. Fibrotest, metabolic assessment and genotyping by Illumina exome array have been performed. DNA, serum and plasma aliquots are stored at -80°C in OASI institute and in CRB-Inserm of CHRU-Nancy/UMRS 1256. Related documents: ethical approval by Ethics Committee, Sicily, Italy, written informed consent.
– The Dantokpa cohort (joint collaboration of Université du Benin and NGERE, PIs N Chabi and JL Guéant) enrolled 428 ambulatory women of the Dantokpa central market of Cotonou (Benin, West Africa). The recruited women were subjected to DNA and blood sampling for genetic, metabolic and biochemical analyses, and to a questionnaire providing information on family history, school status, physical activities, height, weight, waist circumference, hypertension (systolic blood pressure>140 mm Hg), diabetes mellitus, dyslipidemia, non-cardiovascular diseases.
– EDEN. The EDEN mother-child study is a French observational cohort that studied pre and early postnatal determinants of child’s health in the offspring of mothers that were recruited from prenatal clinics at less than 24 weeks of amenorrhea by the Poitiers and Nancy University Hospitals’ departments of Obstetrics and Gynaecology (PI Barbara Heude and Aline Charles, Inserm Unité 1153- CRESS); NGERE is a partner through two international projects (NuTTMeD, co-PI, JL Guéant and ALPHABET, PI, B Heude). The completed child follow-up consisted of data collection from questionnaires and health check-ups at 1, 3 and 5-6 years, in a final number of 1250 mother child dyads. The diet of mothers was assessed by a food frequency questionnaire the year prior to pregnancy and during the last trimester of pregnancy. Plasma and DNA samples were collected from both parents during pregnancy, mother/child dyads at birth and children, aged 5 to 6 years.
– The cohort of SEPT9_SuRV study (PHCRi 2019, PI A Oussalah) is a cohort, which addresses the diagnostic accuracy of biomarkers predictors of HCC occurrence in patients with cirrhosis and NASH. A total of 400 HCC-free patients will be recruited in six hepatology departments in Grand Est region. The patients with NASH-related cirrhosis will represent around 25% (~ 100 patients). Every patient will benefit from a longitudinal follow-up every six months for five years. At each visit, each patient will undergo clinical and biological evaluation along with liver imaging.
– The “Nancy Big-data” sample population (National Commission for Data Protection and Liberties; CNIL N°1763197v0) on more than 35,000 patients attending the University Hospital of Nancy. For each patient, biochemical and bacteriological data were systematically collected in the electronic database and were retrospectively extracted for the purposes of the study, using the GLIMS general laboratory information management system, version 8.11.6 (MIPS France, Paris, France). The “Nancy Biochemical Database” is registered CNIL and approved by the University Hospital of Nancy ethics committee.
Operational platforms for translational and clinical research
– UMS 3286 CNRS-Université de Strasbourg (Director Pascal Villa), Labex Medalis. This UMS will provide: Miniaturized testing of biological effect of compounds using cell models (cell lines and PBMC for cytokine release after LPS-induction, raw cells for nitrite oxidase activity, wound healing, apoptosis, cell proliferation/death…); High-throughput screening of chemical libraries on fully robotized platforms; Conditioning and managing chemical libraries; Structure activity relationship (SAR) expertise following screening with experienced medicinal chemists; Early ADME-Tox studies, including metabolic stability, cellular toxicity, distribution, pharmacokinetic measurements.
– UMS 2008 CNRS-Université of Lorraine-Inserm IBSLor (PI, Iouri Motorine, co-PI, P Lacolley). The Service Unit (UMS) 2008 and its 6 core facilities, including the Functional Genomics Core Facility , which relies on the expertise of the UMR1256 NGERE in the field of NGS sequencing of patients, high throughput genotyping on BeadChip Infinium Illumina chips, study of the methylation of the human genome and bioinformatic analysis of omics data. The Epitranscriptomics & Sequencing (EpiRNA-Seq) core facility performs Next Generation Sequencing (NGS) of RNA.
Clinical research units and platform at CHRU Nancy
Clinical investigation centre in clinical epidemiology, CIC-EC 1433 Inserm/CHRU Nancy/UL (Coordinator: F Guillemin) will provide operative support for cohorts and clinical trials on aspects such as perceived health, diagnosis and prognosis, evaluation of innovative strategies (diagnosis and therapeutics) with a specific proficiency in health economics for health technology assessment.
PARC (Plateforme d’Aide à la Recherche Clinique) (PI, C Baumann) will provide the methodological support and resources in data base management and monitoring of patients for clinical studies. The Platform will use CleanWEB ™ for our multi-center phases I to IV clinical trials, cohorts & epidemiological studies. This tool supports all business processes, including development of eCRF, ePRO, Electronic Data Capture, data cleaning, Clinical Trials Management System, data management (DCF, automated consistency checks, incremental data extraction SAS file (data analysis software used by ESPRI), and the ability to access a secure hosting.
CRB CHU (Coordinator P Rossignol, C Malaplate) is a certified bio bank of the CHU Nancy affiliated to UMRS 1256. In this facility are archived the biological samples of cohorts studied in ARRIMAGE as well as samples from more than 20 inter-regional and national PHRC and other ANR and INCa projects.
Nancyclotep (Dir G Karcher). Nancyclotep-GIE is a molecular imaging platform dedicated to Positron Emission Tomography (PET), located at Nancy University Hospital, whose vocation is research and development, medical activity as well as scientific and economic development. Nancyclotep has the legal status of an Economic Interest Grouping (GIE) which has 3 members: the CHRU of Nancy, the University of Lorraine and the POSIFIT company in charge of recovery and pharmaceutical operations.