MedUni Vienna's Transplantation Research Platform Awards "Start up Grants" to Young Researchers

Awards for Moritz Muckenhuber and David Pereyra

The Transplantation Research Platform of the Medical University of Vienna has awarded two "Startup Grants" to support young scientists in the field of transplant research. Moritz Muckenhuber and David Pereyra receive funding for their projects on pregnancy-induced allo-sensitization and liver transplantation, respectively.

The grants are intended to generate new research results that will serve as a basis for the future acquisition of third-party funding. The awards were presented by Michaela Fritz, Vice Rector for Innovation and Research, and the coordinators of the Transplantation Research Platform, Rainer Oberbauer and Thomas Wekerle.

About Moritz Muckenhuber’s project

During pregnancy, women encounter paternal HLA antigens carried by the semi-allogeneic fetus. As a consequence of the arising immune response, two thirds of women develop HLA-specific antibodies. These antibodies can persist for decades and in the context of transplantation limit donor organ compatibility. Therefore, in clinical reality pregnancy induced allosensitization impacts women’s access to transplantation.

Moritz Muckenhuber will establish a mouse model to investigate the immunological mechanisms that cause and sustain pregnancy induced allosensitization. The results are expected to identify novel therapeutic strategies to specifically target B cell and plasma cell populations that maintain pregnancy induced HLA (MHC)-specific antibodies. Subsequently, the most promising therapeutic approaches will be evaluated in a mouse model for cardiac transplantation.

Overall, Moritz hopes that this project will help to improve transplant care for pre-sensitized patients.

About Moritz Muckenhuber

Moritz Muckenhuber is an MD-PhD candidate in Thomas Wekerle’s research group at the Division of Transplantation of MedUni Vienna's Department of General Surgery. He joined MedUni Vienna’s MD-PhD programme in 2018 and finished his medical studies in 2019. During his PhD in the field of immunology, Moritz investigates therapeutic strategies to overcome costimulation blockade resistant allograft rejection.

About David Pereyra’s project

Liver transplantation is a unique treatment option for a variety of patients suffering from endstage liver disease leading to reduced mortality and extended overall survival in this patient cohort. While the intra- and perioperative management were vastly revolutionized in the past decades, early allograft dysfunction (EAD) on the basis of ischemia/reperfusion injury and impaired liver regeneration still affects a large proportion of patients. Of note, EAD is one main modulator of outcome after liver transplantation while being associated with increased morbidity and early mortality in affected individuals. Of note, novel methods of preoperative liver graft perfusion were shown to reduce the effect of ischemia/reperfusion injury and allowing for more vigorous evaluation of liver viability prior to transplantation, thereby reducing the incidence of EAD and biliary complications. Yet, to date there is no causal treatment option for EAD, as regeneratory patterns are still incompletely understood and successful therapeutic interventions are lacking.

In this context, yes-associated protein 1 (YAP-1) was recently investigated as a main proregenerative factor after toxic injury and loss of functional liver tissue. The majority of studies investigates this context in rodent models. Here, induction and/or activation of YAP-1 lead to increased liver regeneration after partial hepatectomy. Further, an improved outcome after acute toxic liver injury was observed. Of note, the pro-regenerative effect of YAP-1 is suggested to rely on the preservation of biliary integrity rather than on hepatocyte-dependent mechanisms, thereby presenting a specifically interesting target for investigation in liver transplantation, as postoperative biliary complications are known to be frequent.

Within the proposed project, David Pereyra aims to (1) analyze YAP-1 induction and -activation in patients undergoing liver transplantation and evaluate potential associations with postoperative outcome, (2) elucidate the dynamics and relevance of YAP-1 activation during normothermic machine perfusion in a longitudinal fashion and (3) investigate a potentially beneficial effect of YAP-1 activation on hepatic conditioning using pharmacological intervention in a set of three livers which failed viability testing prior to transplantation and subjected to normothermic machine perfusion.

About David Pereyra

David Pereyra completed his studies in the PhD programme (N094) Vascular Biology at the Institute of Vascular Biology and Thrombosis Research at the Centre for Physiology and Pharmacology and the University Department of General Surgery (Supervisors: Alice Assinger and Patrick Starlinger). For his dissertation entitled "Investigation of hemostatic biomarkers for risk prediction in selected human diseases" he was presented with the Award of Excellence by the Ministry of Science in 2022.


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