The research of this group focuses on two broad programs. The first aims to define the cellular and molecular mechanisms governing metastases growth and spread within the liver, a preferential area of metastatic dissemination of tumors of different origin (colorectal, pancreas, lung and breast) often associated with poor prognosis, mostly because of late diagnosis and/or relative inefficiency of current available anti-tumoral drugs. The final goal is to develop new preventive and/or therapeutic approaches for these diseases based on the selective targeting of specialized cellular compartment by type I interferon molecules.
The second deals with the peculiar capacity of hepatocytes, the differentiated cells of the liver to regenerate following acute and chronic liver injury. This group is interested in defining the cellular and molecular mediators associated with liver regeneration under conditions associated with restitution to integrum and in conditions associated with extracellular matrix deposition, with the final goal to design new pharmacological approaches able to increase liver regeneration in patients suffering of acute or chronic hepatic insufficiency.
These programs takes advantage of:
- dedicated mouse models of liver colorectal cancer metastases,
- dedicated mouse models of liver regeneration, such as acetaminophen intoxication and 70% partial hepatectomy
- new technological advances in the field of live imaging [e.g. magnetic resonance imaging (MRI) and optical in-vivo imaging] to develop new preventive and/or therapeutic approaches for these diseases.
Catarinella M, Monestiroli A, Escobar G, Fiocchi A, Tran NL, Aiolfi R, Marra P, Esposito A, Cipriani F, Aldrighetti L, Iannacone M, Naldini L, Guidotti LG, Sitia G. IFNα gene/cell therapy curbs colorectal cancer colonization of the liver acting on the hepatic microenvironment. EMBO Molecular Medicine 2016 Feb 1;8(2):155-70.
Sitia G. Towards personalized medicine in chronic HBV patients? Liver International 2015. DOI: 10.1111/liv.12806.
Aiolfi R, Sitia G. Chronic hepatitis B: role of anti-platelet therapy in the control of inflammation. Cell Mol Immunol. 2015 May;12(3): 264–268.
Sitia G. Platelets promote liver immunopathology contributing to HBV mediated hepatocarcinogenesis. Seminars in Oncology 2014 Jun;41(3):402-5.
Sitia G, Aiolfi R, Di Lucia P, Mainetti M, Fiocchi A, Mingozzi F, Esposito A, Ruggeri ZM, Chisari FV, Iannacone M, Guidotti LG. Anti-platelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B. ProcNatlAcadSci USA. 2012 Aug 7;109(32):E2165-72.
Sitia G, Iannacone M, Aiolfi R, Isogawa M, van Rooijen N, Scozzesi C, Bianchi ME, von Andrian U, Chisari FV, Guidotti LG. Kupffer cells hasten resolution of liver immunopathology in mouse models of viral hepatitis. PLoSPathog. 2011 Jun;7(6):e1002061.
Sitia G, Iannacone M, Mülle S, Bianchi ME, Guidotti LG. Treatment with HMGB1 inhibitors diminishes CTL-induced liver disease in HBV transgenic mice. J LeukocBiol. 2007 Jan;81(1):100-7.
Brown BD*, Sitia G*, AnnoniA, Hauben H, SergiSergi L, Zingale A, Roncarolo MG, Guidotti LG, Naldini L. In vivo administration of lentiviral vectors triggers a type I interferon response that restricts hepatocyte gene transfer and promotes vector clearance. Blood 2007 Apr 1;109(7):2797-805. *Equal contribution.
Sitia G, Isogawa M, Iannacone M, Campbell IL, Chisari FV, Guidotti LG. MMPs are required for the recruitment of antigen-nonspecific mononuclear cells into the liver by CTLs. J Clin Invest. 2004 Apr 15; 113(8): 1158–1167.
Sitia G, Isogawa M, Kakimi K, Wieland SF, Chisari FV, Guidotti LG. Depletion of neutrophils blocks the recruitment of antigen-nonspecific cells into the liver without affecting the antiviral activity of hepatitis B virus-specific cytotoxic T lymphocytes. ProcNatlAcadSci USA. 2002 Oct 15;99(21):13717-22.