Patologia Generale 1

Liver Toxicity: Mechanisms of irreversible primary hepatocyte injury following treatment with oxidative or mitochondrial drugs, hypoxia/reoxygenation and free fatty acids. Analysis of energetic, ionic, pH and volumetric alteration and  of cytotoxic signal mediators. Cytotoxic effects of the distruption of intracellular sodium homeostasis.  “In vivo” studies on: ischemia-reperfusion injury (IRI) and fatty liver injury. Molecular and cellular mechanisms of immuno-lipotoxicity and of IRI. Seminal reports: Carini et al Hepatology 21:1089,1995; Carini et al Exp Cell Research, 248:280, 1999; Rolla et al Clin Sci 130:193, 2016. 

Endogenous Liver Protection: analysis of molecular mechanisms responsible for the induction of the resistance of hepatocyte and of  liver tissue to death upon preconditiong with  sub-lethal stresses. Characterization of survival pathways in preconditioned parenchimal and not parenchimal liver cells. Seminal reports: Carini et al. Hepatology, 31:166, 2000; Carini et al Gastroenterology, 127: 914, 2004; Baldanzi et al 17: 1059, 2010.; Alchera et al Hepatology, 48: 230, 2008; Imarisio et al. Clin Sci, 123 (5): 323, 2012; Mandili et al. J. Hepatol. 62 (3): 573, 2015

 Sodium homeostasis and cancer: differences of regulation of sodium intracellular levels in transformed and non-transformed hepatic cells. Sodium homeostasis and cancer cell survival:  specific sensitivity of cancer cells to an increased sodium intracellular concentration.  Seminal report: Clemente N et al Commun Biol. 2023 May 29;6(1):574.

Sodium homeostasis and cancer (lines of research in progress): Sodium-dependent cancer death: analysis of the different types of cell death involved. Role of sodium homeostasis in cancer cell invasiveness, metastatic potential, cell growth and in cancer cell immuno-cytotoxicity. Sodium-mediated anticancer strategies in immuno-depressed and in immuno-competent mice bearing hepatic and extra-hepatic allograft tumors. Effects of sodium ionophores on hepatic carcinogenesis.

1. Clemente N, Baroni S, Fiorilla S, Tasso F, Reano S, Borsotti C, Ruggiero MR, Alchera E, Corrazzari M, Walker G, Follenzi A, Crich SG, Carini R. Boosting intracellular sodium selectively kills hepatocarcinoma cells and induces hepatocellular carcinoma tumor shrinkage in mice. Commun Biol. 2023 May 29;6(1):574.
2. Alchera E, Chandrashekar BR, Clemente N, Borroni E, Boldorini R, Carini R. Ischemia/Reperfusion Injury of Fatty Liver Is Protected by A2AR and Exacerbated by A1R Stimulation through Opposite Effects on ASK1 Activation. Cells. 2021 Nov 15;10(11):3171.
3. Imarisio C, Alchera E, Bangalore Revanna C, Valente G, Follenzi A, Trisolini E, Boldorini R, Carini R. Oxidative and ER stress-dependent ASK1 activation in steatotic hepatocytes and Kupffer cells sensitizes mice fatty liver to ischemia/reperfusion injury. Free Radic Biol Med. 2017 Nov;112:141-148.
4. Alchera E, Rolla S, Imarisio C, Bardina V, Valente G, Novelli F, Carini R. Adenosine A2a receptor stimulation blocks development of nonalcoholic steatohepatitis in mice by multilevel inhibition of signals that cause immunolipotoxicity. Transl Res. 2017 Apr;182:75-87.
5. Rolla S, Alchera E, Imarisio C, Bardina V, Valente G, Cappello P, Mombello C, Follenzi A, Novelli F, Carini R. The balance between IL-17 and IL-22 produced by liver-infiltrating T-helper cells critically controls NASH development in mice. Clin Sci (Lond). 2016 Feb;130(3):193-203.

Inside UPO  Anatomo-Pathology, Biochemistry, Immunomics, Hystology, and Molecular Pathology Laboratories

Outside UPO:  University of Torino: Department of Molecular Biotechnology and Health Sciences, General Chemistry and Immunology Laboratories

Research Funds from UPO PI: Rita Carini. Project FAR 2017 “RUOLO DI ASK1 NEL DANNO DA ISCHEMIA/RIPERFUSIONE DEL FEGATO STEATOSICO E NELLA PROTEZIONE DA PRECONDIZIONAMENTO: STUDI IN MODELLI PRECLINICI ECLINICI”  

Research Funds from AIRC: PI: Rita Carini. Project IG 2020 ID 24351 “BOOSTING THE INCREASE OF INTRACELLULAR SODIUM TO KILL SELECTIVELY HEPATIC CANCER CELLS: PRECLINICAL PROOF OF CONCEPT”

PI: Rita Carini, PhD Professor of General Pathology 

Postdoc fellowship holder: Francesco Tasso  Master Degree in Biotechnology

PhD student:  Simone Fiorilla  Master Degree in Biology 

Fellowship holder:  Tommaso Trisciuoglio Master Degree in Biology