Carlo Spirli PhD

Assistant Professor of Medicine (Digestive Diseases)

Research Summary

The main focus of my research is the pathophysiology and therapy of diseases of the biliary tree (also called cholangiopathies). This is a large group of chronic liver diseases, congenital or acquired, that causes significant morbility and mortality in both the adult and pediatric population. The pathogenesis of biliary tree diseases is still elusive and, contrary to other areas of hepatology, effective treatment is still lacking. Previous work of our laboratory has contributed to the understanding of the normal physiology of biliary cells and to the identification of prototypic mechanisms for biliary damage for which a model human cholangiopathy exists. Among them, the lab is now addressing the pathophysiology and treatment of Cystic Fibrosis cholangiopathy, polycystic liver disease and Alagille syndrome.

Selected Publications

  • Spirli C, Morell CM, Locatelli L, Okolicsanyi S, Ferrero C, Kim AK, Fabris L, Fiorotto R, Strazzabosco M. Cyclic AMP/PKA-dependent paradoxical activation of Raf/MEK/ERK signaling in polycystin-2 defective mice treated with Sorafenib. Hepatology. In Press
  • Spirli C, Locatelli L, Fiorotto R, Morell CM, Fabris L, Pozzan T, Strazzabosco M.Altered store operated calcium entry increases cyclic 3',5'-adenosine monophosphate production and extracellular signal-regulated kinases 1 and 2 phosphorylation in polycystin-2-defective cholangiocytes. Hepatology. 2012 55:856-68.
  • Spirli C, Okolicsanyi S, Fiorotto R, Fabris L, Cadamuro M, Lecchi S, Tian X, Somlo S, Strazzabosco M. 2010. Mammalian Target of Rapamycin Regulates Vascular Endothelial Growth Factor-Dependent Liver Cyst Growth in Polycystin-2 defective mice. Hepatology 51:1778-88
  • Spirli C, Okolicsanyi S, Fiorotto R, Fabris L, Cadamuro M, Lecchi S, Tian X, Somlo S, Strazzabosco M. 2010. ERK1/2-Dependent Vascular Endothelial Growth Factor Signaling Sustains Cyst Growth in Polycystin-2 Defective Mice. Gastroenterology 138-360-371
  • Strazzabosco M, Fiorotto R, Melero S, Glaser S, Francis H, Spirlì C, Alpini G. 2009. Differentially expressed adenylyl cyclase isoforms mediate secretory functions in cholangiocyte subpopulation. Hepatology 50:244-252.
  • Fabris L., Cadamuro M, Fiorotto R., Roskams T., Spirlì C., Melero S., Sonzogni A., Joplin RE., Okolicsanyi L., Strazzabosco M. 2006. Effects of Angiogenic Factor Overexpression By Human and Rodent Cholangiocytes in Polycystic Liver Diseases. Hepatology 43:1001-1012.
  • Spirlì C., Fiorotto R., Okolicsanyi L., Masier S., Rocchi L., Vairetti MP., De Bernard M., Melero S., Pozzan T., Strazzabosco M. 2005. Glibenclamide stimulates fluid secretin in rodent cholangiocytes through a CFTR-independent mechanism. Gastroenterology 129:220-33.
  • Strazzabosco M, Fabris L, Spirlì C. Pathophysiology of cholangiopathies. 2005. J Clin Gastroenterol. 39:S90-S102.
  • C. Spirlì, L. Fabris, E. Duner, R. Fiorotto, N.F. La Russo, A. Sonzogni, L. Okolicsanyi, Strazzabosco M. 2003. Cytokine-stimulated nitric oxide production inhibits adenylyl cyclase and cAMP-dependent secretion in cholangiocytes.Gastroenterology 124:737-753.

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