2020 Dr. Philipp Schwabl Host Institute

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Sheila Sherlock Post-graduate Fellowship - 2020 Dr. Philipp Schwabl Host Institute: University College London Biography: Philipp Schwabl was born 1988 in Vienna and is working at the Department of Gastroenterology and Hepatology (Head: Michael Trauner) at the Medical University of Vienna for over 10 years. Mentored by Thomas Reiberger, the focus of his work lies in the translational research of liver cirrhosis and portal hypertension. As a physician/scientist Philipp Schwabl has long lasting experience in both, treatment of cirrhotic patients and in-vivo experiments with respective liver disease models. This allows him to investigate novel treatment options for portal hypertension from bench to bedside. In his past works, within the Reiberger group, Philipp studied the hemodynamic effects and the underlying pathophysiological mechanisms of drugs like nebivolol, sorafenib, pioglitazone, PX206065 (non-steroidal FXR agonist) or riociguat (soluble guanylyl cyclase stimulator) in different portal hypertensive models. He also explored the clinical impact of hepatitis C clearance on portal hypertension, and investigated elastography and biomarkers to assess cirrhosis, portal hypertension and respective clinical outcomes. Philipp is also active as a teacher at the Medical University of Vienna and has been the president of the Young Scientist Association at his university. He has acquired funding for several peer-reviewed projects and received national and international awards for his scientific contributions. Research Project: Research Project: Targeting stellate cell contraction to reduce liver tissue tension and treat portal hypertension Hepatic stellate cells (HSC) are pericytes lining the liver sinusoids in the space of Disse. In case of liver damage HSC become contractile. Thus, HSC affect tissue tension and sinusoidal flow, which subsequently promotes inflammation, fibrogenesis and portal hypertension. As this is a key pathophysiological path in many chronic liver diseases, we aim to expand the understanding of HSC biomechanics. To examine the contractile phenotype of human HSCs within liver tissue, they will be cultured in extra-cellular matrix obtained from healthy and cirrhotic patients. On a cellular level, we aim to study signaling pathways mediating HSC contraction and will focus on intracellular calcium dynamics. Further experiments will be performed in 3D printed spheroids allowing non- planar mechanical force investigations. In this setting we will explore the interaction between HSC and the surrounding matrix by analyzing cytoskeletal remodeling and integrin signaling. Dynamic and rapid processes will be visualized using confocal microscopy. We want to elucidate the contractile impact on the extra-cellular matrix and quantify the resulting changes in sinusoidal hemodynamics. Ultimately, we aim to identify specific drug candidates counteracting the HSC strain and thus ameliorate liver fibrosis and portal hypertension..

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