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Role of macrophages in degenerative myopathies and fibrosis.

Pawandeep Singh
Pawandeep SinghUniversity Claude Bernard Lyon 1

I finished my Master of Science degree in Biology from Ludwig Maximilians University, Munich, Germany. My studies were mostly focused on Epigenetics, Human Biology, and Bioinformatics. I applied single-cell RNA sequencing (drop-seq) to identify over 40 different cell types and target cell type of lung fibrosis in humans in my master thesis.

Currently, I am enrolled as a Ph.D. student in EDISS doctoral school in Biology and Health at the University of Claude Bernard Lyon 1 in Lyon, France. My project is focused on identifying subsets of macrophages and identifying their different regulatory pathways between matrix remodeling and fibrosis in Duchenne Muscular Dystrophy (DMD) mouse model.

Lyon 1

University Claude Bernard Lyon 1

France

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Topic

Inflammatory cells control stem cell fate/behaviour coordinating tissue repair by adopting sequential inflammatory profiles.

This tightly regulated balance is skewed in patients with late phases of chronic diseases, like muscle dystrophies.

In degenerative myopathies, unlike in the regenerating muscle, macrophage subsets show mixed phenotypes that exhibit different functions, mixing at the same place subsets that are beneficial for myogenesis and other subsets that are detrimental promoting fibrosis.

However, surface markers allowing to target precisely those subsets, as well as the major signaling pathways controling their behavior, are lacking.

We will investigate this peculiar phenotype by performing single cell RNAseq to identify the precise molecular signature of macrophage subsets in diseased muscle.

Selected identified gene of interest will be deleted through floxed strains with specific macrophage-CRE including LysM, or through electroporation of shRNA to identify their roles in fibrosis and myogenesis. Complementary, in vitro LOF/GOF experiments in co-cultures of fibroblasts and myoblasts will be performed to validate the role of these macrophage-regulatory pathways on the regulation of of matrix remodelling versus fibrosis.

Objectives
  • To decipher the role of different macrophage subsets in matrix remodelling/fibrosis in normal and diseased muscle

  • To identify differential regulatory pathways between matrix remodelling and fibrosis

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