IPPRITT – Individual Profiling and Prevention of Risks with Immunosuppressive Therapies and Transplantation
UMR Inserm-CHU 1248


Presentation

Pierre MARQUET – Director
Tel. : + 33 (0)5 55 05 60 17

Adress : Centre de Biologie et de Recherche en Santé (CBRS), 2ème étage Rue du Pr. Bernard Descottes 87025 LIMOGES Cedex

Website

Administrative SupervisionUniversity of LimogesInsermCHU of Limoges

Parent Institute : GEIST

Doctoral School : ED 615 – Biological Sciences and Health (SBS)

Federative structureFHU SUPORT (SUrvival oPtimization in Organ Transplantation) with Poitiers (U1082 “Ischemia-Reperfusion in organ transplantation”) and Tours (EA4245 “dendritic cells, immune modulation and transplantation”)

Key figures (30/06/2017)

Professors & researchers: 23
Engineers, Technicians, administratif staff: 7
Doctoral Students: 8
Accreditated to direct research (HDR) : 11

38 people present

Scientific Publication (2012-2016)

International peer reviewed journal: 227
Thesis defended : 15

> WEBSITE PUBLICATION

Current Projects

ANR: ROCKET (Reclassification using OmiCs integration in KidnEy Transplantation)

National projects in coordination: PHRC national « Transplantation utérine » 2015; « tolérance à l’ischémie prolongée de l’utérus de brebis » AO recherche 2016 de l’Agence de la BioMédecine ; « EPIPHITe, EPIgénétique et Pharmacologie des Immunosuppresseurs en Transplantation », AO recherche 2016 de l’Agence de la BioMédecine

International projectsFP7 BIOMARGIN, BIOMARkers of Renal Graft Injuries (coordinator) ; « Precision Medicine can PREVENT AMR », financé par Genome Canada ; IMMUSTICATRE, Programme Hubert Curien avec l’Algérie (coordinator)

Other projects: « Modeling membrane crossing of drugs used in transplantation », APREL 2016 CHU of Limoges (coordonnator)

Research

The UMR 1248 Joint Research Unit carries out translational research on drugs used in transplantation with the aim of optimizing their benefit/risk balance, based on a personalized medicine approach. This research focuses on : Identifying pharmacokinetic, pharmacogenetic, pharmacodynamics and environmental factors of (therapeutic and toxic) treatment response variability. • Setting-up tools for compensating this variability or for the prevention or treatment of adverse events • Validating the clinical and medico-economic benefit of these personalized medicine tools.

Research themes:

  • Biomarker axis : Investigation of the pharmacodynamic biomarkers of immunosuppressive drugs (ISD), particularly calcineurin inhibitors (CNI, cyclosporine, tacrolimus) that may help to individualize patient treatments – Study of the toxic mechanisms of CNI on renal tubules (chronic renal allograft dysfunction) – Search for early urine biomarkers of kidney graft lesions – Biomarkers in liver transplantation
  • Pharmacogenomics axis : Involvement of rare exon variants in extreme phenotypes in transplantation by whole-exome sequencing – ISD effects on epigenetic marks and epigenetic status effects on ISD response.
  • Pharmacometrics axis : –Molecular modelling of trans-membrane transfers of anti-CMV drugs and ISD – Development of pharmacokinetic models and Bayesian estimators for ISD and clinical validation – Clinical transfer of these tools through the unit’s expert system “ExpertIS” and website ISBA (https://pharmaco.chu-limoges.fr) – Development of models for the prediction of graft and patient outcomes based on multicentric, retrospective and prospective cohort studies – Pharmaco-epidemiologic study of transplanted patient adherence, adverse effects, quality of life and their determinants – Pharmaco-economic study of different therapeutic strategies in transplantation.
  • Therapeutic innovation axis: Uterus transplantation

Keywords:

Pharmacokinetics ; Pharmacogenetics ; Biomarkers ; Toxicity ; Pharmacoepidemiology ; Translational Research ; Clinical Research ; Transplantation ; Immunosuppressive Drugs

Equipment / Technical resources

Mass spectrometry ; Proteomic analysis ; PCR, real-time PCR ; Cell culture ; Molecular biology ; Pharmacokinetic modelling, disease modelling, molecular modelling

Scientific valorization

Fields of application : Health, pharmacy, bio-industry (phamacology, organ transplantation)

Industrial applications: The ABIS/ISBA website on individualized dosing for transplant patients, developed based on the UMR 1248 results, received over 9,000 requests in 2014, from more than 54 transplant units, including a dozen foreign units (Europe, North America, South America and North Africa). The site’s activity in France is financed through inter-hospital invoicing. (https://pharmaco. chu-limoges.fr). In 2019, this activity and another telemonitoring application issued from the unit’s works will be transferred to the unit’s spin-off company Optim’Care

Chair of ExcellencePharmacologie de la Transplantation

ClusterEuroBioMed

Partnerships

  • National University Partnerships: Vast collaborative network with organ transplantation centres (e.g., 7 renal transplantation centres involved in our EPHEGREN study) ; Pharmacogenetics: Prof. D Anglicheau, U845 INSERM, Hôpital Necker, Paris ; Proteomics and biomarkers: 6 French partners in the FP7 BIOMARGIN programme
  • International University Partnerships : FP7 BIOMARGIN: Partners in Germany, Belgium, Sweden and The Netherlands ; Pharmacology of ISD: partnerships with Profs. P Wallemacq, V Haufroid & M Mourad, Cliniques Saint-Luc, Belgium ; and Profs. T van Gelder and R van Schaik, Erasme Hospital, The Netherlands ; Pharmacodynamics of ISD: Prof. Patricia Espéron, university of the republic of Uruguay (Ofelia Noceti’s thesis co-direction) ; Prof. Mercedes Brunet, Hospital Clinic of Barcelona, Spain ; PK and PK/PD modelling: M Neally & R Jelliffe, L.A. PK lab, USC, USA ; Disease modelling: N. Holford, Univ. Auckland, New Zealand ; Molecular modelling: Regional Center of Advanced Technologies and Materials (Olomouc, Czech Republic); Institut für Chemie, Technische Universität Berlin (Berlin, Germany); Laboratory for Chemistry of Novel Materials (Mons, Belgium) ; Clinical transfer of personalized medicine tools via the unit’s ISBA website, used by a dozen international transplant units (European, American, Asian and North African)
  • National Industrial Partnerships: Clinical research contracts with Sandoz, Astellas and Chies
  • International Industrial Partnerships: Partnerships with Mosaïques Diagnostics (Germany) et AcureOmics (Sweden) and Sandoz Europe (Germany)