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Study of the molecular mechanism of Endothelial to Mesenchymal Transition during muscle regeneration and crosstalk with the immune system in vivo and in vitro.

Filipa Timoteo Ferreira
Filipa Timoteo FerreiraUniversity of Milano- Bicocca

I am a PhD student from Translational and Molecular Medicine program in UNIMIB DIMET.

I graduated from Biochemistry and completed my MSc in Medicine and Molecular Oncology by the University of Porto, Portugal.

I am developing my PhD project under Professor Silvia Brunelli supervision in the area of muscle regeneration and aging RENOIR. The research will provide information about EC progenitors during muscle injury in an altered inflammatory environment and the molecular mechanisms involved in endothelial to mesenchymal transition, including their crosstalk with the immune system during muscle regeneration.

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University of

Milano – Bicocca

 Italy

Topic

Several studies support the emerging concept that inflammation controls stem cell fate/behaviour coordinating tissue repair and this balance is probably skewed in patients with late phases of chronic diseases, like muscle dystrophies.

This project will focus on how the inflammatory and vascular components integrate to coordinate muscle regeneration and how the process of Endothelial to Mesenchymal Transition (EndoMT) contributes to fibrosis in pathological conditions .

To investigate the molecular mechanism of EndoMT in vivo, we will FACS-sort endothelial derived cells and macrophages from endothelial cells (ECs) specific lineage tracing mice in different EndoMT inducing conditions and at different time points.

We will investigate the pathways activated in pathological EndoMT by RNA and protein expression analyses, including RNAseq, and upon specific inhibition to identify new pathways that could serve as potential therapeutic targets.

We will also perform genome-wide epigenetic analyses of EC progenitors and macrophages to gain insight into their chromatin state and into the dynamic changes of chromatin during EndoMT, and correlate this with the transcriptional profile.In addition, we will contribute to the optimization of an in vitro systems to study the interaction between endothelial progenitors and macrophages.

Objectives
  • To characterize EC progenitors in vivo during muscle injury in an altered inflammatory environment
  • To characterize signalling pathways and the chromatin landscape in EC progenitors and macrophages during EndoMT in acute muscle regeneration

  • To develop new in vitro systems to mimic the vascular niche and macrophage-vascular progenitor interactions to dissect signalling pathways

PHD Program

Translational and Molecular Medicine (DIMET)

University of Milano Bicocca

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