Location: DIBIT2 A2, Floor 5
Senior postdoc, Chromatin dynamics Unit
Junior team leader, Chromatin dynamics Unit
Tissue damage occurs in a variety of medical conditions, such as physical injuries, infections, or diseases. The injured tissues release intracellular molecules, Damage-Associated Molecular Patterns (DAMPs), which are essential for protection of the host and tissue healing. The study of these sophisticated molecules has great medical relevance, because their involvement has been extensively reported in numerous pathological conditions, from cancer to inflammatory disorders. The Unit is particularly interested in HMGB1, an archetypal DAMP that was originally identified as a nuclear protein involved in chromatin dynamics and gene transcription. Besides its nuclear functions, HMGB1 is also released by dead or stressed cells to signal “danger” to surrounding cells and to trigger inflammation.
Our group demonstrated that our organism uses HMGB1 in alternative redox forms to orchestrate sequential physiological processes after tissue injury— signaling damage, triggering inflammation, and eventually promoting regeneration. Of most direct utility, we identified a non-oxidizable mutant form of HMGB1 as a promising drug candidate to promote tissue repair without exacerbating inflammation.
Our main current interests are to elucidate the contribution of HMGB1 to tissue repair and homeostasis in chronic pathological conditions, such as muscular dystrophies or muscle wasting associated to cancer progression, and to uncover the fate of released HMGB1. We combine in vivo (transgenic mice, mouse models of tissue damage, muscular dystrophies, cancer) and in vitro (primary stem cells, tumor cells) models together with biochemistry and molecular biology tools to unravel mechanistic insights on how HMGB1 triggers cell- specific responses to coordinate tissue repair and homeostasis.
Giorgia Careccia, PhD student
Immavaleria Faldello, student
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, Ronfani L. Seeing is not always believing: lessons from knockout mice. J. Leuk. Biol. 2017 Feb; 101(2):353-356.
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, 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.
2004- 2008 PhD in Immunology, INSERM U564, University of Angers, France.
2003- 2004 Postgraduate Degree in Cell Biology, University of Poitiers, INSERM U564, Angers, France.
2000-2003 Three-year Master’s Degree in Cell Biology & Physiology, University of Angers, France.
1999-2000 First year of medical school, University of Angers, France.
2017-present Teaching "Molecular cell biology and Genetics & Biology of Development" to MD students at Università Vita-Salite San Raffaele, Milan (Italy).
2014-present Junior Team Leader at IRCCS Ospedale San Raffaele, Chromatin Dynamics Unit, Milan, Italy.
2011-2012 Teaching "Molecular cell biology" to international MD students at Università Vita-Salute San Raffaele, Milan, Italy.
2010-2011 Teaching "Molecular Biology" to Master students in ISTIA, Angers (France).
2008-2014 Postdoctoral fellow at IRCCS Ospedale San Raffaele, Chromatin Dynamics Unit, Milan, Italy.
2018-present Trampoline Grant from AFM-Telethon (PI).
2018-present Triennal Grant from Italian Ministry of health (Co-PI).
2014-2018 Grant for Young Investigators from Italian Ministry of health (PI).
2011-2013 Postdoc fellowship from Italian foundation for cancer research.
2007-2008 PhD fellowship from French foundation for medical research.
2004-2007 PhD fellowship from French Ministry of Higher Education and Research.