Project

CONNECTION

Chondroitin sulfate proteoglycan‐4, secreted by a binding imbalance between SP1 and NF‐kB on CHST11 gene, triggers sympathetic cardiac denervation in Duchenne Muscular Dystrophy
Application Areas
Research Areas
Research Lines
Staff
WEBSITE

ITB Principal Investigator

Name

Chondroitin sulfate proteoglycan‐4, secreted by a binding imbalance between SP1 and NF‐kB on CHST11 gene, triggers sympathetic cardiac denervation in Duchenne Muscular Dystrophy

Acronym

CONNECTION

Location

Segrate

Start Date

2020

End Date

2024

Funder

FONDAZIONE REGIONALE PER LA RICERCA BIOMEDICA

Partners

- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - "Sapienza" University of Rome, Rome, Italy (Prof. R. Rizzi) - Institute of Physical Chemistry - Polish Academy of Sciences, Warsaw, Poland (Dr M. Costantini) - University of North Carolina, North Carolina, USA (Prof. G. Dotti) - National Institute of Molecular Genetics (INGM) “Romeo and Enrica Invernizzi” - Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Napoli, Italy (Dr C. Parisi)

The project is focused on investigating cardiomyopathy in Duchenne muscular dystrophy (DMD), a severe genetic disorder caused by the absence of dystrophin. The research explores the mechanisms linking inflammation, pathological extracellular matrix remodeling, and alterations in cardiac innervation, which are key processes in myocardial damage progression. Particular attention is devoted to the role of dystrophic macrophages and to the molecular pathways involved in extracellular matrix regulation. The project integrates advanced approaches in transcriptomics, proteomics, and bioengineering to identify new therapeutic targets. Its main lines of development include the use of CRISPR-dCas9 technology, the generation of CSPG4.CAR-T cells, and the creation of an innovative 3D neuro-cardiac junction model. Overall, the project aims to clarify the mechanisms underlying cardiac damage in DMD and to foster the development of new therapeutic strategies.
  • Ceraolo MG, et al. CSPG4.CAR-T Cells Modulate Extracellular Matrix Remodeling in DMD Cardiomyopathy. Int J Mol Sci (2025) 26(14):6590. doi: 10.3390/ijms26146590.
  • Chirivì M, et al. “Mimicking the Dystrophic Cardiac Extracellular Environment through DystroGel”. Adv Healthcare Mater (2025) 2404251. https://doi.org/10.1002/adhm.202404251.
  • Stirm M, et al. A scalable, clinically severe pig model for Duchenne muscular dystrophy. Dis Model Mech (2021) 14(12):dmm049285. doi:10.1242/dmm.049285. Epub 2021 Dec 16.