Carlo Spirli, PhD

Associate Research Scientist
Section of Digestive Diseases

Training

• Undergraduate Student, Laboratory of Hepatology, Institute of Internal Medicine, University of Padova, Italy (1991-1995).
• Pre-Doctoral Fellow, Laboratory of Hepatology, Institute of Internal Medicine, University of Padova, Italy (1995)
• Ph.D. Student, School of Medicine, University of Parma, Italy (1995-1999)
• Post-Doctoral Fellow, Institute of General Pathology, University of Vienna, Austria (October 1997- July 1998)
• Visiting Scientist, Liver Center, Yale University, USA (August 1998; January-February 2001; December 2004).
• Visiting Scientist, Center for Basic Research in Digestive Diseases, Mayo Clinic, USA (January-February 2002)
• Associate Researcher, Department of Medical and Surgical Sciences, University of Padova, Italy (June 2000-April 2004)
• Associate Researcher, Center for Liver Research, Division of Gastroenterology, Ospedali Riuniti di Bergamo, Italy (July 2004- December 2005)
• Associate Research Scientist, Dept Internal Medicine Digestive Diseases Section, Yale University, USA. (January 2006-)

Research Interests

Epithelial Cell Biology, Pathophysiology of Diseases of the Biliary Tree, Liver Cell Therapy.

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

• M. Strazzabosco, C. Poci, C. Spirlì, A. Knuth, L. Sartori, G. Crepaldi. 1994. Effect of Ursodeoxycholic acid (UDCA) on intracellular pH in a bile duct epithelium-like cell line. Hepatology 19: 145-154.
• M. Strazzabosco, C. Poci, C. Spirlì,  A. Zsembery, A. Granato, ML. Massimino and G. Crepaldi. 1995. Intracellular pH regulation in Hep G2 cells. Effects of  epidermal growth factor, transforming growth factor-a and insulin-like growth factor II on  Na+/ H+ exchange activity. Hepatology 22/2: 588-597.
• M. Strazzabosco, R. Joplin,  Zsembery, L. Wallace, C. Spirlì, L. Fabris, A. Granato, A. Rossanese, C. Poci, J.M. Neuberger and G. Crepaldi. 1997. Cl-/HCO3- Exchange mediate cellular HCO3-  transport in cultured human intrahepatic bile duct cells. Hepatology  25:976-985
• A. Zsembery, C. Spirlì, A. Granato, N.F. LaRusso, L. Okolicsanyi, G. crepaldi, M. Strazzabosco.1998. Autocrine purinergic regulation of transepithelial H+/HCO3- transport in cholangiocytes. Hepatology:28:914-20
• C. Spirlì, A. Granato, A. Zsembery, F. Anglani, L. Okolicsanyi, N.F. LaRusso, G. Crepaldi, M.Strazzabosco.1998. Functional polarity of Na+/H+ exchange and Cl-/HCO3- exchange in a differentiated rat cholangiocyte cell line (NRC-1). Am J Physiol 275:G1236-G1245
• M. Strazzabosco, C. Spirlì, L. Okolicsanyii. 2000. Pathophysiology of the intrahepatic biliary epithelium. J Gastroenterol Hepatol. 15: 244-253
• C. Spirlì, M.H. Nathanson, R.  Fiorotto, E. Duner, L.A. Denson, J.M. Sanz, F. Di Virgilio, L. Okolicsanyi, F. Casagrande, M. Strzzabosco. 2001. Proinflammatory Cytokines inhbit secretion in rat bile duct epithelium. Gastroenterology 121:156-169
• A. Zsembery, W, Jessner, G. Sitter, C. Spirlì, M. Strazzabosco, J. Graf. 2002. Correction of defective CFTR function and stimulation of Ca2+-activated Cl- channels restore bicarbonate secretion in cystic fibrosis human bile ductular cells. Hepatology 35:95-104
• S. Melero, C. Spirlì, A. Zsembery, JF. Medina, RE. Joplin, E. Duner, M. Zuin, JM. Neuberger, J. Prieto, M. Strazzabosco. 2002 Defective regulation of Cl-/HCO3- and Na+/H+ exchange activities in cholangiocytes isolated from patients with primary biliary cirrhosis. Hepatology 35:1513-1521
• 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.
• Strazzabosco M, Fabris L, Spirlì C. Pathophysiology of cholangiopathies. 2005. J Clin Gastroenterol. 39:S90-S102.
• 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
• Marra F, DeFranco R, Robino G, Novo E, Efsen E, Pastacaldi S, Zamara E, Vercelli A, Lottini B, Spirlì C, Strazzabosco M, Pinzani M, Parola M. 2005. Thiazolidinedione treatment inhibits bile duct proliferation and fibrosis in a rat model of chronic cholestasis. World J Gastroenterol 11:4931-8.
• 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

Contact

Campus Address
Department of Internal Medicine
P.O. Box 208023
20 York St. EP 2-611
New Haven, CT 06520-8023

E-mail
carlo.spirli@yale.edu