ESR6

Epigenomics of macrophage phenotypes and the contribution of transcription processes contributing to phenotype switch.

Noemi Caballero Sanchez
Noemi Caballero SanchezUniversity of Debrecen

Noemí Caballero Sánchez is PhD Student at the Faculty of Medicine at the University of Debrecen. This doctorate program is associated with the European Training Network RENOIR which main goal is the study of muscle regeneration and aging.

She graduated in Biotechnology followed by a MSc in Molecular and Cellular Biology and Genetics. During her education, Noemí took part in several projects, in which she could gain practical experience in techniques and technologies commonly used in molecular and cellular biology, but also meant a great opportunity to reinforced and improved her knowledge in bioinformatics.

Currently, she is a member of the Nuclear Hormone Receptor Research Laboratory in the Department of Biochemistry and Molecular Biology of the University of Debrecen lead by László Nagy, who is the supervisor of the project. The major objective is the study of gene expression, epigenomics and immunophenotype changes that take place in macrophages along the muscle regeneration process.

University of Debrecen

University of Debrecen

Hungary

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Topic

The progressive failure of muscle repair and an altered inflammatory response can lead to fibrosis that in turn can also negatively influence stem cells functionality.

Macrophages (MPs) subsets show mixed phenotypes that exhibit different functions mixing 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 study the epigenetic changes underlying the transition from inflammatory to repair MPs in both acute (CTX) and chronic (mdx) muscle injury on FACS-isolated Ly6Chi and Ly6Clow (and specific subsets identified according to the markers identified above) MP populations using single cell and bulk approaches at various time points at various time points. ATAC-seq experiments will be carried out to determine the open chromatin regions along with ChIP-seq of active (H4Ac and H3K27Ac) and repressive (H3K27Met3) histone marks.

We will built an epigenomic landscape dataset. Transcriptomic analyses will be also carried out from the same populations and changing gene sets and their genomic regulators will be determined using the bioinformatics pipelines developed at UNIDEB. The candidate transcription factors will be prioritized and their suitability as targets evaluated.

In a separate set of studies, candidate transcription factors will be analysed for their contribution of MPs gene expression and immunophenotype, including the heme-regulated transcription factor, BACH-1. Using BACH-1 KO mice we will carry on transcriptomic analyses on MPs and the involvement of the BACH-1 mediated pathways in disease progression will be identified by intersecting the datasets derived from wild type animals and DMD models.

Objectives
  • To isolate and characterize the chromatin structure of inflammatory Ly6Chi and repair Ly6Clow MPs from models of acute injury and DMD using ATAC-seq and ChIP-seq

  • To identify transcriptional regulatory molecules and pathways controlling the transition from inflammatory to repair MPs using RNA-Seq

  • To mechanistically dissect the role and contribution of select transcription pathways (BACH-1) using LOF studies in vivo to MPs assisted muscle repair in acute injury and in models of DMD

PHD Program

Molecular Cell and Immune Biology Faculty of Medicine

University of Debrecen

Supervisor

László Nagy

University of Debrecen

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