Project 9

Inflammation and chronic fibrosis

ESR9: Maria Parlani

Stichting Radboud Universitair Medisch Centrum, Radboud Institute for Molecular Life Sciences (Netherlands)

Supervisors: Pr P. Friedl, co-supervisors: local: Dr K. Wolf, external: academic: Dr. P. Bousso (P3, Pasteur), non-academic: J. Heidlin (LVBT)

Objectives: Study the kinetic distribution and migration patterns of leukocytes and stromal cells in the foreign body response model for chronic inflammation: intravital multiphoton microscopy (iMPM) monitoring of transgenic or antibody labelled cell systems, including monocytes/macrophages (e.g., TRAP/dtTomato), myofibroblasts (a-SMA/mCherry), and blood vessels (dextran). Aims: 1) Monitor macrophage and T cell interaction with stromal fibroblasts in early and late-stage fibrosis. 2) Identify molecular drivers of fibrosis by RNAseq. 3) Interfere with identified molecular drivers (2-3), using knockout and antibody/small molecule inhibitor strategies. will be assessed and quantitatively reconstructed in 3D+t.

Expected Results: Disrupt the macrophage-fibroblast interactome; prevent/revert the fibrotic response.

Secondments: Academic: P2 Leiden Dr.M. Varela, Month 12, 1 Month, autophagy detection, P5 ELTE: Prof. T Vicsek, Month 18, 4 months: multiparameter computational modeling. Industrial: P14 LaVisionBioTec: Dr. J. Heidelin, Month 16, 1 month: advanced multiphoton microscopy systems.