ESR3
Role of macrophages in degenerative myopathies and fibrosis.

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.
University Claude Bernard Lyon 1
France
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University Claude Bernard Lyon1 (UCBL)
The University Claude Bernard Lyon 1 (UCBL) is the fifth largest French university, and the 1st one in the field of health, taking into account the number of students.
The UCBL student population is nearly 40 000, and it employs 2900 teachers/researchers and teachers, of which 700 are also hospital practitioners, as well as 1800 technical and administrative staff. The University has 73 state-funded research units working in three fields; health, the environment and material technologies. It is a multidisciplinary university specializing in both fundamental and applied research and as such it can boast more than 4415 internationally published articles and 44 patents per year. UCBL currently hosts 11 ERCs, 48 FP7-H2020 programs among which 21 in Biology and Health Sciences.
The Institut NeuroMyoGene (INMG) is located in the School of Medicine, nearby the biggest Hospitals of Lyon. This institute is a new research centre, opening on January 1rst 2016 and belonging to University Lyon1. This centre is in large part dedicated to neuromuscular physiology and pathology and gather basis scientists and clinicians to develop translational and preclinincal research. INMG includes 14 research teams, among which 4 ERCs, that actively participate in teaching and mentoring predoctoral and doctoral programmes at University Claude Bernard Lyon 1 in the two life sciences doctoral schools of the university.
The ESR will be enrolled in the PhD programme from EDISS School in Biology and Health in biology and health (http://www.ediss-lyon.fr/), at University of Lyon.
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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
PHD Program
EDISS School in Biology and Health
University of Lyon
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