Silvia Brunelli - Associate Professor
Department and institution: Department of Health Sciences, School of Medicine and Surgery, University of Milano Bicocca
tel. +39 02 64488308
institutional profile page: UNIMIB
lab's website: HEVA research
see also: PubMed, BOA, ResearchGate, Scopus Author ID 7003321841, Linkedin
Keywords: Tissue regeneration, muscle homeostasis, innate immunity, vascular progenitors, fibrosis.
Regeneration of muscle fibers, lost during pathological muscle degeneration or after injuries, is sustained by generation of new myofibers, Progenitors in the muscle comprise quiescent myogenic cells, the satellite cells, that are primary stem cells responsible for skeletal muscle regeneration after damage and vessel-associated progenitors, such as the mesoangioblasts (MAB). Using a genetic lineage tracing approach, a transgenic mouse expressing an inducible Cre under the control of an endothelial specific promoter we have provided new insights on the distinctive characteristics of the extraembryonic and embryonic hemogenic endothelium and we have identified for the first time the in vivo counterpart of embryonic MAB (Azzoni et al, 2014).
We also shown that macrophages are necessary for efficient vascular remodeling in the injured muscle. When phagocyte infiltration is compromised endothelial-derived progenitors undergo a significant endothelial to mesenchymal transition (EndoMT). This together with an inefficient tissue remodeling contributes to the accumulation of collagen, fat and significant fibrosis. Our findings provide new insights in EndoMT in the adult skeletal muscle, and suggest that endothelial cells in the skeletal muscle may represent a new target for therapeutic intervention in fibrotic diseases (Zordan et al, 2014). We are extending these studies to diseases, both of genetic and acquired origin such as Fibrodysplasia Ossificans Progressive (FOP) (Tirone et al, 2019).
Main topics of the group
Molecular Mechanisms of Muscle regeneration, Endothelial to Mesenchymal Transition in Development and Diseases
Current research projects
-Cellular and Molecular characterization of the infiltrating polarized macrophage during the onset of heterotopic ossification in a mouse model of Fibrodysplasia Ossificans Progressiva
Funding: FOP Italia
Partners: Renata Bocciardi, Gaslini, Genova
-REcreating the ideal Niche: environmental control Of cell Identity in Regenerating and diseased muscles
Funding: Marie Skłodowska-Curie Actions (MSCA) Innovative Training Networks (ITN) H2020-MSCA-ITN-2019
Partnerss: RENOIR network (https://renoir-itn.eu)
Internal and external collaborators
Selected Recent Publications
Severe Heterotopic Ossification in the Skeletal Muscle and Endothelial Cells Recruitment to Chondrogenesis Are Enhanced by Monocyte/Macrophage Depletion. Tirone M, Giovenzana A, Vallone A, Zordan P, Sormani M, Nicolosi PA, Meneveri R, Gigliotti CR, Spinelli AE, Bocciardi R, Ravazzolo R, Cifola I, Brunelli S. Front Immunol. 2019 Jul 19;10:1640. doi: 10.3389/fimmu.2019.01640. eCollection 2019.
High mobility group box 1 orchestrates tissue regeneration via CXCR4. Mario Tirone, Ngoc Lan Tran, Chiara Ceriotti, Andrea Gorzanelli, Monica Canepari, Roberto Bottinelli, Angela Raucci, Stefania Di Maggio, César Santiago, Mario Mellado, Marielle Saclier, Stéphanie François, Giorgia Careccia, Mingzhu He, Francesco De Marchis, Valentina Conti, Sabrina Ben Larbi, Sylvain Cuvellier, Maura Casalgrandi, Alessandro Preti, Bénédicte Chazaud, Yousef Al-Abed, Graziella Messina, Giovanni Sitia, Silvia Brunelli, Marco Emilio Bianchi and Emilie Vénéreau. J Exp Med. 2018 Jan 2;215(1):303-318. doi: 10.1084/jem.20160217
Macrophages Guard Endothelial Lineage by Hindering Endothelial-to-Mesenchymal Transition: Implications for the Pathogenesis of Systemic Sclerosis. Pier Andrea Nicolosi, Enrico Tombetti, Anna Giovenzana, Eleonora Donè, Eleonora Pulcinelli, Raffaella Meneveri, Mario Tirone, Norma Maugeri, Patrizia Rovere-Querini, Angelo A Manfredi, Silvia Brunelli. J Immunol. 2019 Jul 1;203(1):247-258. doi: 10.4049/jimmunol.1800883.