Hepatic Inflammation and Metabolic Health
Prof. Ronit Shiri-Sverdlov
PO Box 616
6200 MD Maastricht
T: (+31) (0)43 3881746
Ronit Shiri-Sverdlov studied Biology in Tel-Aviv University (Israel), where she received her PhD degree in 2002 on the basis of defining the spectrum of genetic mutations related to breast and ovarian cancer. In 2002 she moved to Maastricht University and worked as postdoctoral fellow at the department of Molecular Genetics. Shortly after her transition to Maastricht, she received a VENI NWO ZonMw fellowship that she used to in order to establish her work on non-alcoholic steatohepatitis (NASH). In addition to several other grants she received a VIDI NWO ZonMw fellowship in 2012 and subsequently became an associate professor within Maastricht University.
Ronit has full accountability for all aspects of research, staff and finances in the group, including contribution to education (group leader and PI). She ensures the efficient, timely and correct execution of all the projects. She controls activities in terms of planning, budgeting, auditing and monitoring. She is in charge of ensuring continuity in the research efforts and is responsible for monitoring the possibility of generating intellectual property. Ronit is also responsible to promote the transfer of knowledge with commercial value or societal returns into the clinic and industry. In addition to her scientific obligations, Ronit is actively involved in education in the Biomedical Sciences FHML and in the Dutch and international track for medical students as a lecturer, tutor, member of planning group and coordinator.
Nutritional factors affecting non-alcoholic steatohepatitis (NASH)
Non–alcoholic steatohepatitis (NASH) is the hepatic event of the metabolic syndrome and is characterized by steatosis (fat accumulation) and inflammation. Whereas steatosis is harmless, the inflammatory component can lead to irreversible liver damage. However, the mechanisms by which inflammation is triggered are unknown. Our aims are to identify the molecular mechanisms that trigger inflammation in NASH and related metabolic diseases, to establish innovative non-invasive markers for hepatic inflammation and to identify novel treatment options for hepatic inflammation and related diseases.
Our experiments span from basic to translational science and include both mouse and human studies.The results are expected to influence a wide area of research related to metabolic syndrome as well as fields with similar mechanisms. As such, knowledge gained in this project has enormous market potential and that substantial commercial exploitation is expected.
In Maastricht, we collaborate mainly with prof. W. Buurman, P. Lindsey PhD, J. Plat PhD and prof. A. Bast. We also have a strong collaboration with clinicians specialized in liver disease (prof. S. Olde Damink, prof. K. Dejong and G. Koek PhD). A longstanding collaboration exists with prof. M. Hofker (Groningen), prof. D. Lütjohann (Bonn, Germany), prof. E. Latz (Bonn, Germany) and C.J. Binder PhD (Vienna, Austria).
Bieghs V, Hendrikx T, van Gorp PJ, Verheyen F, Guichot YD, Walenbergh SM, Jeurissen ML, Gijbels M, Rensen SS, Bast A, Plat J, Kalhan SC, Koek GH, Leitersdorf E, Hofker MH, Lütjohann D, Shiri-Sverdlov R. The cholesterol derivative 27-hydroxycholesterol reduces steatohepatitis in mice. Gastroenterology. 2013 Jan;144(1):167-178.e1
Bieghs V, van Gorp PJ, Walenbergh SM, Gijbels MJ, Verheyen F, Buurman WA, Briles DE, Hofker MH, Binder CJ, Shiri-Sverdlov R. Specific immunization strategies against oxidized low-density lipoprotein: a novel way to reduce nonalcoholic steatohepatitis in mice. Hepatology. 2012 Sep;56(3):894-903
Bieghs V, Wouters K, van Gorp PJ, Gijbels MJ, de Winther MP, Binder CJ, Lütjohann D, Febbraio M, Moore KJ, van Bilsen M, Hofker MH, Shiri-Sverdlov R. Role of scavenger receptor A and CD36 in diet-induced nonalcoholic steatohepatitis in hyperlipidemic mice. Gastroenterology. 2010 Jun;138(7):2477-86, 2486.e1-3
Hendrikx T, Jeurissen ML, Bieghs V, Walenbergh SM, van Gorp PJ, Verheyen F, Houben T, Guichot YD, Gijbels MJ, Leitersdorf E, Hofker MH, Lütjohann D, Shiri-Sverdlov R. Hematopoietic overexpression of Cyp27a1 reduces hepatic inflammation independently of 27-hydroxycholesterol levels in Ldlr(-/-) mice. Journal of Hepatology (2015), Feb;62(2):430-6
Hendrikx T, Watzenböck ML, Walenbergh SM, Amir S, Gruber S, Kozma MO, Grabsch HI, Koek GH, Pierik MJ, Staufer K, Trauner M, Kalhan SC, Jonkers D, Hofker MH, Binder CJ, Shiri-Sverdlov R. Low levels of IgM antibodies recognizing oxidation-specific epitopes are associated with human non-alcoholic fatty liver disease. BMC Medicine (2016), 22;14(1):107
Houben T, Brandsma E, Walenbergh SM, Hofker MH, Shiri-Sverdlov R. Oxidized LDL at the crossroads of immunity in non-alcoholic steatohepatitis. Biochimica et Biophysica Acta. - Molecular and Cell Biology of Lipids (2016), pii: S1388-1981(16)30202-5
Walenbergh SM, Houben T, Hendrikx T, Jeurissen ML, van Gorp PJ, Vreugdenhil AC, Adriaanse MP, Buurman WA, Hofker MH, Mosca A, Lindsey PJ, Alisi A, Liccardo D, Panera N, Koek GH, Nobili V, Shiri-Sverdlov R. Plasma cathepsin D levels: a novel tool to predict pediatric hepatic inflammation. American Journal of Gastroenterology (2015), Mar;110(3):462-70
Walenbergh SM, Koek GH, Bieghs V, Shiri-Sverdlov R. Non-alcoholic steatohepatitis: the role of oxidized low-density lipoproteins. J Hepatol. 2013 Apr;58(4):801-10
Wouters K, van Gorp PJ, Bieghs V, Gijbels MJ, Duimel H, Lütjohann D, Kerksiek A, van Kruchten R, Maeda N, Staels B, van Bilsen M, Hofker MH and Shiri-Sverdlov R. Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis. Hepatology. 2008 Aug;48(2):474-86
1 technician, 5 PhD students