Master 2 – Multiorgan-on-chips and IPSCs applied to Pharmacology

Nicolas Védrenne

Florent DI MEO

INSERM U1248 IPPRITT

CBRS – Université de Limoges

1, rue du Pr Bernard Descottes

87000 Limoges

Deadline:  01/11/2021

Documents:

• Resume
• Cover Letter

Funding:

Yes

Over the past decades, personalized medicine within the context of pharmacology have been an active field of research. Understanding of individual patient response is key to personalized medicine in order to e.g., improve the drug benefit-risk balance. This is particularly true in the context of organ transplantation therapy using Calcineurin inhibitors such as tacrolimus. For instance, the unexplained variability in immunosuppressant drug response and toxicity still remains important in spite of the identification of many factors of variability. The combination of multiple low- to mild-penetrance factors is very likely to at least partially address this variability. Nowadays, conventional pharmacological research approaches (including pharmacodynamics – PD – studies) still struggle to confirm or even identify these factors. 

In this context, the present project aims at developing an expert system based on multi-organs-on-chips devices in order to accurately describe (i) remote inter-organ communication between liver and kidney as well as (ii) the impact of tacrolimus metabolism on tubular tissue (including both structural and cellular transport features). From the technical point of view, the multi-organs-on-chips system will be build using two approaches considering either induced pluripotent stem cells (iPSCs) or commercially available cell lines. In situ tacrolimus metabolism will be investigated as well as its impact on tubular structure and cellular transport.

Keywords: System Pharmacology – Organ-on-a-chip – Cellular and Membrane Transport – Pharmacokinetics – Pharmacodynamics  – IPSCs