Research award for project on heart transplantation

Heart failure is one of the leading causes of morbidity and mortality worldwide. In the most severe cases, heart transplantation is the sole option for improving quality of life and survival. However, every year the number of patients on heart transplantation waiting lists increases, while the number of donor hearts remains stable. Thus, there is an urgent need to find additional donors for cardiac grafts. To address the organ shortage, interest in donation after circulatory death (DCD) has been revived. More than 100 DCD heart transplantations have been reported worldwide in the last 5 years, and outcomes to date are excellent.

Although its feasibility has been demonstrated, DCD heart transplantation raises concerns as it is accompanied by a damaging period of warm ischemia (stopping of blood supply) prior to organ procurement. Ischemia and subsequent reperfusion (return of blood flow) are particularly detrimental for the heart, and mitochondria are one of the most sensitive cellular organelles. Under normal conditions, mitochondria are the cellular factories responsible for generating the energy required for maintaining cellular function and viability.

However, mitochondria are damaged by warm ischemia and reperfusion. This damage results in their inability to produce sufficient energy for heart contraction, their production of damaging free radicals, and their release of components, called mitochondrial damage-associated molecular patterns (mtDAMPs), which activate inflammatory processes. Importantly, the research team of the Department of Cardiovascular Surgery has recently reported that mtDAMPs are released by DCD hearts following warm ischemia and early-reperfusion levels correlate with subsequent contractile recovery.

With her future research, Dr Sanz will use a pre-clinical model of DCD to characterize the pattern of release of mtDAMPs, and to investigate their role in inflammatory responses and recovery of contractile function in cardiac grafts. The activation of inflammatory responses is of particular importance in heart transplantation as they may ultimately contribute to graft rejection. In her studies, Dr Sanz will give special attention to mitochondrial DNA, the most pro-inflammatory mtDAMP, which has been detected in high levels in the circulation of human DCD donors.

This work comprises a larger line of research for which Dr Sanz was recently awarded a Research Fellowship from The International Society of Heart and Lung Transplantation. A better understanding of the role of mtDAMPs in cardiac ischemia and reperfusion should aid in the optimization of clinical protocols for DCD heart transplantation, ultimately improving outcomes for patients with severe heart failure.

Maria-Nieves Sanz (born in 1982) studied biology at the University of Salamanca (Spain), where she completed her PhD in 2010 with the highest honor and the European Doctorate Mention. During her doctoral studies, she investigated the direct effects of oral antidiabetic drugs on hepatic mitochondria. After graduating, she moved to Paris (France) where she completed two post-doctoral positions; firstly, at the Laboratory of Physiopathology of AMPK and AMPK-related protein kinase in Diabetes and Obesity in Institut Cochin (2011-2013), and subsequently at the Laboratory of Signaling and Cardiovascular Pathophysiology in the University of Paris Sud (2013-2015). In Paris, Dr Sanz extended her work on the regulation of cellular metabolism and mitochondrial biology to cardiovascular disease. In 2015, she received a Research Grant from the European Society of Cardiology to join the research team of the Department of Cardiovascular Surgery, under the direction of Prof. Dr. Dr. Thierry Carrel and PD Dr. Sarah Longnus at Inselspital (Bern).

Since then, her research has focused on the identification of novel, mitochondrial-based therapeutic tools to improve cardiac tolerance to ischemia and reperfusion, with the ultimate goal of improving patient outcomes in heart transplantation.

This work, published in the American Journal of Transplantation, demonstrated that mitochondrial changes underlie differing cardioprotective reperfusion strategies and was awarded 3rd prize for basic research by the Swiss Transplantation Society in 2019.

The Department for BioMedical Research (DBMR) of the Faculty of Medicine of the University of Bern, led by Prof. Dr. med. Mark Rubin, was established 25 years ago by the University of Bern and the Inselspital (Bern University Hospital). To realize its mission to bridge the gap between bench and bedside, the DBMR promotes an integrative perspective to clinical research with a strong emphasis in the development of translational approaches, the use of omics and other cutting-edge technologies, and extensive interaction and collaboration between laboratory-based and patient- oriented clinical research. The DBMR is also committed to fostering the careers of young academics.

Further information: https://www.dbmr.unibe.ch/index_eng.html

Since 1996 the Department for BioMedical Research (DBMR) has held a “Day of BioMedical Research”. This year’s event took place on Wednesday, November 13.

The DBMR provides the best possible conditions to the researchers of the Inselspital and of the Faculty of Medicine of the University of Bern. The annual “Day of BioMedical Research” has established itself as a forum for researchers to present their work in a poster session and to get insights into the research projects of their colleagues.

The event is open to the public, and gives an insight into the clinical research activities at the University of Bern. The “Day of BioMedical Research” is also an excellent platform for making new contacts and exchanging ideas.

Further information: https://www.dbmr.unibe.ch/research/the_day_of_biomedical_research_2019/index_eng.html

The Fondation Johanna Dürmüller-Bol has donated the CHF 30,000 Research Prize since 2012 and will continue to support the Department for BioMedical Research DBMR until 2021. The Fondation aims to motivate and support young researchers from the Medical Faculty of the University of Bern in its fields of funding Medicine and Science. The project must be submitted by a researcher who is working at the Medical Faculty of the University of Bern and has not qualified as a professor, and it must be a clinically oriented project.

More information on the Fondation Johanna Dürmüller-Bol: https://fjdb.ch/

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