Inflammation and lipid signaling for novel diagnosis and treatment of metabolic diseases
Lipids are a group of hydrophobic compounds that are generally found compartmentalized and serve as a major energy source of the body. Other lipid-related functions range from regulatory functions (i.e. hormones; bile acid precursors) to serving as structural component of the cell and its organelles (i.e. phospholipids and cholesterol). Due to these multiple functions, lipids play a central role in a large range of disorders. Among different physiological processes that are affected by lipid disturbances, inflammation is likely one of the most important. While designed to detect damage and foreign invading factors, the inflammatory response is dysregulated when lipid disturbances arise such as under obese conditions during which patients exhibit a chronic low-grade inflammatory response.
The goal of our research is to provide new diagnostic and therapeutic targets for a wide range of metabolic diseases (see figure below which diseases we focus on) by unraveling their pathometabolic basis. We collaborate with national and international public and private partners to accelerate the development of tangible products for patients.
Past PhD thesis defences within our group:
2021 Tulasi Yadati, Small Molecules, Big Consequences: Novel Therapeutic Approaches for Treating Chronic Inflammatory Diseases
2021 Lingling Ding, The entanglement of plasma Cathepsin D and metabolic disturbances: relevant insights in the metabolic syndrome
2020 Albert Bitorina, Inconspicuous offender: Pathophysiological role of oxidized-low density lipoprotein in metabolic diseases
2018 Tom Houben, Lysosomes ‘in control’: where lipids meet inflammation in metabolic syndrome
2017 Jieyi Li, Macrophage stimulating protein (MSP) in the metabolic syndrome
2017 Mike Jeurissen, The entanglement of NASH and atherosclerosis: shared features of a macrophage-specific response
2016 Sofie Walenbergh, Storage solutions: novel ways for the detection and inhibition of non-alcoholic steatohepatitis
2015 Tim Hendrikx, Intracellular traffic jam: cholesterol accumulation as cause for chronic inflammatory diseases
2011 Veerle Bieghs, Kupffer cells in fatty liver disease: Does size really matter?
2008 Kristiaan Wouters, Non-alcoholic steatohepatits: second hit or strike out?
- Magro Dos Reis I, Houben T, Oligschläger Y, Bücken L, Steinbusch H, Cassiman D, Luetjohann D, Westerterp M, Prickaerts J, Plat J, Shiri-Sverdlov R. Dietary plant stanol ester supplementation reduces peripheral symptoms in a mouse model of Niemann-Pick type C1 disease. J Lipid Res. 2020 Apr 14.
- Ding L, Goossens GH, Oligschlaeger Y, Houben T, Blaak EE, Shiri-Sverdlov R. Plasma cathepsin D activity is negatively associated with hepatic insulin sensitivity in overweight and obese humans. Diabetologia. 2020 Feb;63(2):374-384.
- Bitorina AV, Oligschlaeger Y, Shiri-Sverdlov R, Theys J. Low profile high value target: The role of oxLDL in cancer. Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Dec;1864(12):15818.
- Houben T, Oligschlaeger Y, Bitorina AV, Hendrikx T, Walenbergh SMA, Lenders MH, Gijbels, MJJ, Verheyen F, Lütjohann D, Hofker MH, Binder CJ, Shiri-Sverdlov R. Blood-derived macrophages prone to accumulate lysosomal lipids trigger oxLDL-dependent murine hepatic inflammation. Sci Rep 2017 Oct2;7(1):12550.
- 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 Med 2016 Jul22;14(1).
- 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. Am J Gastroenterol 2015 Mar;110(3):462-70.
- 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 PH, 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 non-alcoholic steatohepatits in hperlipidemic mice. Gastroenterology 2010 Jun;138(7):2477-86.
- 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, Shiri-Sverdlov R, Hofker MH. Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of non-alcoholic steatohepatitis. Hepatology 2008 Aug;48(2):474-86.
- Methods for the treatment of nonalcoholic steatohepatitis; Patent No. TEMP/E-1/47465/2017.
- Methods and compounds for the treatment of Niemann-Pick Disease Type C1.
- (patent number 330 EPP0; date filing: 27.03.2016, published as WO 2017/162806 A1) à continued to Europe and US à 17712159.7 (EU)
- Method for treating non-alcoholic steatohepatitis. (patent number 329 EPP0; date filing: 23.02.2016)
- Method for the treatment of lysosomal lipid storage diseases. (patent number EP13163419.8; date filing: 11.04.2013)
- Method for treating fatty liver diseases, in particular non-alcoholic steatohepatitis. (patent number WO 2012/019930 A1; date filing: 30.07.2011, international publication date: 16.02.2012)
- Method for diagnosing fatty liver diseases, in particular non-alcoholic steatohepatits. (patent number EP2418285 A1; date filing: 09.08.2010, international publication date: 15.02.2012).
- Method for treating liver inflammation, fibrosis and non-alcoholic steatohepatitis. (patent number EP11155267.5; date filing: 21.02.2011)
- Phytosterols and phytostanols for the prevention of treatment of inflammation. (patent number 11191776.1-1216, date filing: 02.12.2011)
- Method for diagnosing of pediatric NASH (patent number EP14188909.7, date filing: 14.10.2014, WO 2016/059054)
Prof. Dr. Ronit Shiri-Sverdlov
Research group members:
Dr. Tom Houben (assistant professor), Dr. Albert Bitorina (researcher), Mengying Li (PhD student), Hester van Mourik (PhD student), Annemarie Westheim (shared PhD student with Dr. Jan Theys)