Tissue regeneration and homeostasis
Tissue regeneration is a well-orchestrated process that occurs after injury caused by disease, physical trauma or infection, among others. The injured tissues release intracellular molecules, called Damage- Associated Molecular Patterns (DAMPs), which are essential for protection of the host and tissue healing. The Unit is particularly interested in HMGB1, a DAMP originally identified as a nuclear protein involved in chromatin dynamics, that also acts as a signal of tissue damage when extracellularly released. We demonstrated that alternative redox forms of HMGB1 orchestrate sequential physiological processes after tissue injury—signaling damage, triggering inflammation, and promoting regeneration. Of most direct utility, we generated a designer HMGB1 as a drug candidate to promote tissue repair without exacerbating inflammation.
Our main interest is to gain a deeper understanding of the cellular and molecular mechanisms that coordinate tissue regeneration and homeostasis. Our current research activities are focused on the regeneration of skeletal muscle from physiological to acute and chronic pathological conditions such as muscular dystrophies and muscle wasting associated to cancer. We combine in vivo mouse models (muscular dystrophies, stem cells transplantation, tumorigenesis) with the most up to date molecular, cellular and imaging procedures to unravel mechanistic insights underlying the regenerative process and the maintenance of tissue homeostasis, and to evaluate the therapeutic relevance of our findings in preclinical models.
We offer PhD positions in two curricula: Cellular and Molecular Biology Basic and Applied Immunology and Oncology. For further details on the PhD program click here.
Careccia G, Saclier M, Tirone M, Ruggieri E, Principi E, Raffaghello L, Torchio S, Recchia D, Canepari M, Gorzanelli A, Ferrara M, Castellani P, Rubartelli A, Rovere-Querini P, Casalgrandi M, Preti A, Lorenzetti I, Bruno C, Bottinelli R, Brunelli S, Previtali SC, Bianchi ME, Messina G and Venereau E. Rebalancing HMGB1 redox isoforms expression to counteract muscular dystrophy. Sci Transl Med. 2021 Jun 2;13(596)
Ferrara M, Chialli G, Ferreira LM, Ruggieri E, Careccia G, Preti A, Piccirillo R, Bianchi ME, Sitia G, Venereau E. Oxidation of HMGB1 is a dynamically regulated process in physiological and pathological conditions. Front Immunol. 2020 Jun 24;11:1122.
Careccia G, Colombo F, Tirone M, Agresti A, Bianchi ME, Zambrano S, Vénéreau E. Exploiting Live Imaging to Track Nuclei During Myoblast Differentiation and Fusion. J Vis Exp. 2019 Apr 13;(146)
Tirone M, Tran NL, Ceriotti C, Gorzanelli A, Canepari M, Bottinelli R, Raucci A, Di Maggio S, Santiago C, Mellado M, Saclier M, François S, Careccia G, He M, De Marchis F, Conti V, Ben Larbi S, Cuvellier S, Casalgrandi M, Preti A, Chazaud B, Al-Abed Y, Messina G, Sitia G, Brunelli S, Bianchi ME and Vénéreau E. High Mobility Group Box 1 orchestrates tissue regeneration via CXCR4. J Exp Med. 2018 Jan 2;215(1):303- 318.
Bianchi ME, Crippa MP, Manfredi AA, Mezzapelle R, Rovere Querini P and Venereau E. High-mobility group box 1 protein orchestrates responses to tissue damage via inflammation, innate and adaptive immunity, and tissue repair. Immunological Reviews. 2017 Nov;280(1):74-82.
Di Candia L, Gomez E, Venereau E, Chachi L, Kaur D, Bianchi ME, Challiss J, Brightling CE, Saunders RM. HMGB1 is upregulated in the airways in asthma and potentiates airway smooth muscle contraction via TLR4. Journal of Allergy and Clinical Immunology. 2017 Aug;140(2):584-587.
Venereau E, De Leo F, Mezzapelle R, Careccia G, Musco G, Bianchi ME. HMGB1 as biomarker and drug target. Pharmacol Res. 2016 Sep;111:534-44.
Venereau E, Ceriotti C, Bianchi ME. DAMPs from Cell Death to New Life. Front Immunol. 2015 Aug 18;6:422.
Choi HW, Tian M, Song F, Venereau E, Preti A, Park SW, Hamilton K, Swapna GV, Manohar M, Moreau M, Agresti A, Gorzanelli A, De Marchis F, Wang H, Antonyak M, Micikas RJ, Gentile DR, Cerione RA, Schroeder FC, Montelione GT, Bianchi ME, Klessig DF. Aspirin's Active Metabolite Salicylic Acid Targets High Mobility Group Box 1 to Modulate Inflammatory Responses. Mol Med. 2015 Jun 18;21:526-35.
Venereau E, Schiraldi M, Uguccioni M, Bianchi ME. HMGB1 and leukocyte migration during trauma and sterile inflammation. Mol Immunol 2013 Aug;55(1):76-82.
Venereau E, Casalgrandi M, Schiraldi M, Antoine DJ, Cattaneo A, De Marchis F, Liu J, Antonelli A, Preti A, Raeli L, Shams SS, Yang H, Varani L, Andersson U, Tracey KJ, Bachi A, Uguccioni M, Bianchi ME. Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release. J Exp Med. 2012 Aug 27;209(9):1519-28.
Schiraldi M, Raucci A, Martínez Muñoz L, Livoti E, Celona B, Venereau E, Apuzzo T, De Marchis F, Pedotti M, Thelen M, Varani L, Mellado M, Proudfoot A, Bachi A, Bianchi ME and Uguccioni M. HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4. J Exp Med. 2012 Mar 12;209(3):551-63.
Mittal D, Saccheri F, Venereau E, Pusterla T, Bianchi ME, Rescigno M. TLR4 mediated skin carcinogenesis is dependent on immune and radioresistant cells. EMBO J. 2010 Jul 7;29(13):2242-52.