Pharmacology of ImmunoSuppressive Drugs and of Transplantation (PIST)
UMR INSERM 850


Contact

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

Administrative Supervision : Université de Limoges INSERM

Parent Institute : GEIST

Doctoral School : ED 524 – Bio-Santé

Key figures (31/12/2015)

Professors : 11
Other researchers : 8
Accreditated to direct research (HDR) : 10
Doctoral Students : 11
Engineers, Technicians, administratif staff : 7

Scientific Publication (2011-2014)

Peer reviewed journal : 126

Thesis defended : 9

Conference presentations : 79

> WEBSITE PUBLICATION

Economic Added Value (2011-2014)

Current National Project : 2

Current european project : 1 – FP7 BIOMARGIN (BIOMARkers of Renal Graft INjuries, coordination)

Number of industrial or research agreements with major organizations : Abbott France, Hoffman-La Roche Ltd (Arabie Saoudite), Roche Pharma France

Conferences, seminars organized : 1

Competitiveness clusters with which the laboratory is associated : EuroBioMed

Presentation

The UMR 850 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

“Pharmacodynamics” 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 vascular endothelium (allograft vasculopathy) and renal tubules (chronic renal allograft dysfunction) – Search for early urine biomarkers of kidney graft lesions “Pharmacogenomics” axis : – Involvement of genetic polymorphisms in the protein targets of ISD (CNI and mTOR inhibitors): o In the variability of cell and clinical responses o In the occurrence of post-transplantation lymphoproliferative diseases (PTLD) – Identification of rare exon variants in precocious PTLD through 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 ; Pharmaco-economy ; Translational Research ; Clinical Research ; Transplantation ; Immunosuppressive Drugs

Honours

Pierre Marquet : “Pippenger Award for outstanding contributions to Therapeutic Drug Monitoring” – International Association of Therapeutic Drug Monitoring and Clinical Toxicology ( 2009 ) Patrick Trouillas : Award of the best foreigner scientist of the Regional Center of Advanced Technologies and Materials – Czech Rep. ( 2014)

Equipment / Technical resources

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

Partnerships

Active National University Partnerships : FHU SUPORT with Poitiers (U1082 “Ischemia-Reperfusion in organ transplantation”) and Tours (EA4245 “dendritic cells, immune modulation and transplantation”) ; 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 Current 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 : Contracts with Roche Pharma, Novartis, Astellas. International Industrial Partnerships : Contracts with Hoffman-Laroche Israël, Astellas Germany, Thermo-Electron USA, Shimadzu Germany Partnerships with National Organizations and Institutions : INSERM ; CHU (University Hospital) of Limoges

Industrial applications

The ABIS/ISBA website on individualized dosing for transplant patients, developed based on the UMR-S850 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)