Translational and Experimental Liver Laboratory

Forschungsschwerpunkt

Molecular Aspects of Liver Cancer & Regeneration

Liver resection is considered the only curative treatment option for several neoplastic entities of the liver. Despite substantial improvements in surgical techniques and peri-operative care, post-operative failure of liver regeneration and concomitant liver dysfunction remain an important concern after partial hepatectomy. In hepatobiliary surgery, this is of major clinical relevance as patient outcome correlates with the potential of the remnant liver to regenerate. In particular, postoperative liver failure represents a frequently fatal postoperative complication with very limited therapeutic options. In this context, it is of crucial importance to understand the complex process of liver regeneration. Indeed, the potential of the liver to regenerate after resection is unique and orchestrated by a combination of highly redundant effector molecules, as blockage of a single molecule only delays but does not stop the process. It is known that a variety of bioactive molecules are involved in liver regeneration. In the past decades, essential insights in mechanisms of hepatic regeneration have been unraveled and several mediators of these mechanisms have been explored in detail. Furthermore, thrombocytes have been found to play a crucial role, not only during the initiation period, but throughout all phases of liver regeneration. In this context, hepatobiliary surgery struggles with two major obstacles:

• to identify patients at risk of postoperative liver dysfunction and concomitant major, potentially lethal, complications prior to surgery;
• to identify patients with highly aggressive disease, that will not benefit from liver resection due to rapid recurrence of the tumor.

In both cases surgery should be omitted as there is no benefit for these patients. However, to date no reliable marker is available to predict patient outcome and postoperative tumor relapse.

Main research objectives of the group:

a)    Molecular mechanisms of liver regeneration and potential treatment targets:

• Identification of central regulators and processes involved in the initiation of liver regeneration.
• Characterization of regulatory mechanisms and thereby identification of novel therapeutic targets to support the regenerative capacity after liver resection as well as to improve our understanding of the pathophysiological processes involved in liver regeneration.

b)    Predictive and prognostic markers for liver regeneration and primary and secondary liver cancer:

• Identification of clinical and experimental markers of liver regeneration which reflect the prognosis of regenerative capability and therefore the postoperative outcome after liver surgery, to ultimately tailor surgical strategy to each individual patient and thereby avoid potentially fatal complications.
• Quantification of tumor aggressiveness using clinical and experimental markers to predict early disease recurrence, to spare unnecessary surgery in patients that will not benefit from tumor resection.

c)    Cancer development:

• Identification of the role of platelets and immune cells and their interaction during the development of liver cancer and progression.

Labormitarbeiter:innen/Team

Christoph Koeditz

Stefan Schuster

Michael Schodel

Kim Sarang

Nguyen Toni

Felix Hubner

Anna Kern

Clara Krimmel

Publikationen

Grants

March 2012 Hans and Blanca Moser research grant (9.000,-)

• Project: "The Role of Tie2 Expressing Monocytes in anti-VEGF Therapy"

September 2012 Georg-Stumpf research grant 2012 (10.000,-)

• Project: „The Role of Platelets and Platelet derived Serotonin in Liver Regeneration of Patients Undergoing Hepatectomy”.

Okt 2015 Research Grant from the Scoiety of the Study of Liver Tumors (8.000,-)

• Project: “Micro RNA Expression and Postoperative Liver Regeneration in Humans.”

April 2016 Innovationsscheck – Development of new diasgnostic markers (12.500,-)

• Project: “The role of circulating micro RNAs during liver regeneration”

June 2018 HepatomiR - FFG with TAMIRNA (600.000,-  Gesmtvolument: 1.300.000,-) role: Co-PI

Feb 2019 Grant of the Mayor of Vienna (25.000,-)

Mai 2019 FWF Project funding – In collaboration with Alice Assinger (350.000,-)

• Project: “The theragnostic potential of microRNAs in liver regeneration“ role: Co-PI

Okt. 2019 Center of Biomedical Discovery, Mayo Clinic – In collaboration with Rory Smoot (15.000,-)

• Project: “Augmenting YAP Activation to Accelerate Liver Regeneration” role: Co-PI

Feb 2020 Regenerative Medicine Minnesota Research Grant – In collaboration with Rory Smoot (250.000,-)

• Project: “Activating The Hippo Pathway Effector YAP to Augment Liver Regeneration” role: Co-PI

July 2020  NIH – R01(total funding: 2.162.000,-)

• Project: “Novel coagulation-dependent mechanisms of liver regeneration to detect and prevent liver dysfunction after partial hepatectomy” role: Co-PI (consorium of 3 with James Luyendyk and Ton Lisman)

 Sept 2021 Wiener Wirtschaftsagentur – Innovation 18-21+, in Kollaboration mit TAMIRNA, Hepatomir (200.000,-)

Klinische Studien

Von Willebrand Factor to Predict Postoperative Outcome

• ClinicalTrials.gov Identifier: NCT02118545 (completed)
  patrick.starlinger@meduniwien.ac.at

Plasma and Hemodynamic Markers During Hepatectomy

• ClinicalTrials.gov Identifier: NCT01700231 (completed)
  patrick.starlinger@meduniwien.ac.at

Platelets in Liver Regeneration

• ClinicalTrials.gov Identifier: NCT02113059 (ongoing)
  patrick.starlinger@meduniwien.ac.at

Steering and writing committee of the 1527-GITCG-IG

DREAM – Diffusion-weighted Magnetic Resonance Imaging Assessment for Liver Metastasis to improve Surgical planning“ joined ESSO-EORTC-JCOG trial

• ClinicalTrials.gov Identifier: NCT02781935 (ongoing)
  patrick.starlinger@meduniwien.ac.at