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Einstein BIH Visiting Fellow project, funded by Stiftung Charité
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The Stiftung Charité will fund our project “Vascular Composite Tissue Allotransplantation (VCA): An integrated, multidisciplinary basic and clinical research program for hand and uterus transplantation” (Einstein BIH Visiting Fellowship) within the framework of the Private Excellence Initiative Johanna Quandt for two more years!

The Charité has a long tradition as an international leader in transplantation. Prior to starting our Einstein BIH funded project in February 2017, Vascular Composite Tissue Allotransplantation (VCA) was neither object of scientific investigations, nor offered to patients. As an Einstein BIH Visiting Fellow Prof. Stefan G. Tullius, Harvard Medical School, ignited both: a basic research group in this field and a clinical research transplant program. During the first three years of our multidisciplinary basic and clinical research program, we have been able to implement complex small animal models (mouse hindlimb, heart, skin transplant models); a rat uterus transplant model is currently established. Those models offer unique opportunities to address basic research questions of translational relevance including: organ-specific alloimmune responses, immunogenicity, and the maternal-fetal interface in uterus transplantation.
An enthusiast clinical, multi-disciplinary has been established, led and mentored by Prof. Tullius that has brought preparatory surgical exercises and clinical algorithms for VCA at the Charité on the way.

Stiftung Charité is an independent charitable foundation. It was endowed in 2005 by entrepreneur Johanna Quandt, who entrusted it with the mission of supporting the innovative potential and excellence of Berlin’s university medicine, which can look back on a rich tradition in medical research and patient care. Thereby, the foundation is active in two focal areas: promoting technology transfer between the laboratory and the clinic as well as improving the framework conditions for innovation and entrepreneurship in medicine. Since 2014, Stiftung Charité is also funding the life sciences in Berlin by its Private Excellence Initiative Johanna Quandt.
EUROSTARS project
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Within the Eurostars project „Comprehensive qualitative/quantitative multi-pathogen IVD workflow for immunocompromised patients (Im-compr-IVD)“ an IVD workflow covering sample preparation up to clinical relevant diagnosis of infection in immunocompromised patients will be developed. Deliverables are:
  • Design, development and preclinical validation of QIC-Finder assay with novel primers and probes for qualitative and quantitative screening of 23 pathogens (bacterial, viral, fungal and parasitic);
  • Detection instrumentation and interpretation software optimized for assay performance;
  • Instructions for high quality DNA/RNA extraction from plasma.
Partners are Pathofinder (Netherlands, Coordinator), Ella Biotech (Germany), IT-IS International Ltd. (United Kingdom) and Charité - Universitätsmedizin Berlin.

Eurostars projects are co-funded by EUREKA member countries and the European Union Horizon 2020 Framework program.
DFG Research Grant for PD Dr. Moritz Schmelzle
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Priv.-Doz. Dr. Moritz Schmelzle receives additional financial support for his project "CD39-dependent regulation of innate immune responses and modulation of exacerbated sterile inflammation in acute-on-chronic liver failure" (DFG Research Grant 299534341, SCHM2661/3-2).
Acute on chronic liver failure (ACLF) is defined as an acute hepatic insult in patients with chronic liver disease and is characterized by high death rates. Systemic inflammation is considered a hallmark of ACLF and can be linked to progression of liver failure and clinical deterioration. Criteria for ACLF and the systemic inflammatory response syndrome (SIRS) substantially overlap and support the assumption of mechanistic similarities between both syndromes. Thus, modulating inflammation and the linked immune responses in ACLF might help to restore homeostasis and improve of regenerative capacities of the injured liver.We hypothesize that the catalyzed hydrolysis of purinergic damage-associated molecular patterns (DAMPS), such as extracellular ATP, by the ectonucleotidase CD39 is crucially involved in the regulation of innate immune responses and the modulation of exacerbated sterile inflammation in ACLF. We here aim to describe characteristics and functions of monocyte subsets in ACLF and to investigate implications of purinergic signaling. We further plan to investigate the therapeutical relevance of non-classical monocytes and the immune-type ectonucleotidase CD39 in experimental ACLF. Finally, we will evaluate the clinical significance of cellular and non-cellular immune responses in ACLF patients enrolled in the GRAFT Trial.
DFG grant for Linda Feldbrügge
Dr. Linda Feldbrügge receives a research grant from the Deutsche Forschungsgemeinschaft (DFG) for her project "Purinergic regulation of inflammation in liver fibrosis by ectonucleoside triphosphate diphosphohydrolase-3 (ENTPD3)“.

ENTPD3, expressed by macrophages and various other cell types, modulates inflammation and tissue regeneration by scavenging extracellular ATP and ADP. As demonstrated by her preliminary work, ENTPD3 appears to play a deleterious role in liver fibrosis. Her new project aims to define the mechanisms of ENTPD3 mediated modulation of macrophage function and regulation of liver fibrosis, and test their relevance in human liver fibrosis.

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SFB 1365 Renoprotection
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The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) is establishing ten new Collaborative Research Centres (CRCs, Sonderforschungsbereich, SFB) to further support top-level research in Germany.
Chronic kidney diseases and acute kidney damage are widespread and reduce the life expectancy of those affected. The CRC “Renoprotection” therefore aims to decode specific signalling pathways for kidney damage and develop new approaches to treatment in the long term (Charité Berlin – FU Berlin and HU Berlin, Spokesperson: Prof. Dr. Pontus Börje Persson).
With the project "Renoprotective role of Lipocalin-2 in allograft rejection following kidney transplantation" Priv.-Doz. Dr. Felix Aigner and Dr. Muhammad Imtiaz Ashraf, PhD will be part of this SFB/CRC!

To provide allograft renoprotection, novel strategies are needed, including (i) prevention of renal allograft IRI and (ii) targeted immunosuppression and thus; reduction and avoidance of steroid and CNI usage in the long-run. Using a mouse model of kidney transplantation, we recently demonstrated a renoprotective role of exogenously administered recombinant Lcn2:Siderophore:Fe complex (rLcn2). The rLcn2 mediated mechanism of allograft renoprotection is still unknown; however, the mechanistic insight is essential for comprehensive translation of the rLcn2 therapy into clinical practice. In the funded project, we aim at (i) understanding the route and mechanisms of immunoregulation and/or cytoprotection, mediated by exogenously administered rLcn2 during the allograft damage; and (ii) characterizing the source and nature of endogenous Lcn2 i.e. whether it is complexed with mammalian iron binding catechols and may contribute to allograft survival in the long-run. Our ultimate goal is to pave the way for transplant renoprotection via recombinant Lcn2.

More information…
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Mathilde Feist and Paul Ritschl: Clinician Scientists
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Dr. Mathilde Feist and Dr. Paul Ritschl successfully applied for the BIH Charité Clinician Scientist Program. Mathilde Feist will work on "Cytokine-armed oncolytic vaccinia virus for pancreatic cancer therapy". Mentors are Prof. Bahra, Prof. Sauer and Prof. Beling.
Paul Ritschl focusses on "The Impact of Donor Derived Microparticles Following Solid Organ Transplantation". Mentors are Priv.-Doz. Dr. Schmelzle and Priv.-Doz Dr. Öllinger.
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Wibke Schulte: BIH Charité Clinician Scientist
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Dr. med. Wibke Schulte successfully applied for the BIH Charité Clinician Scientist Program with her project „Die Rolle von MIF in der humanen akuten Peritonitis | Role of MIF in human acute peritonitis“. Mentors are Priv.-Doz. Dr. med. Felix Aigner and Prof. Dr. Igor M. Sauer.
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Barbara Kern: BIH Charité Clinician Scientist
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Dr. Barbara Kern successfully applied for the BIH Charité Clinician Scientist Program. With her project "Novel Treatment and Diagnostic Approaches Utilizing the Role of Dendritic Cells in Immune Responsivness" Barbara will be engaged in our Vascular Tissue Allotransplantation Initiative (Project VCA). The Clinician Scientist Program is a modern career pathway within academic medicine that allows physicians to pursue a structured residency with time set aside for clinical and basic research. At the end of the program, participants will have completed their residency and, ideally, their postdoctoral teaching qualification (Habilitation). The program is intended to produce a new generation of scientists with translational training who will help speed up the rate at which scientific findings are translated into application.
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ECRT - Advanced Scientist Grant
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PD Dr. Nathanael Raschzok receives one of the 2017 Einstein Center for Regenerative Therapies (ECRT) Kickbox – Advanced Scientist Grant.
Einstein Center for Regenerative Therapies Kickbox – advanced scientist grant. The project is entitled „Overcoming steatotic compromise – Reconstitution of endogenous repair in severely steatotic liver grafts by metabolic reconditioning“. The project will be conducted by Nathanael Raschzok, Angelika Kusch, Duska Dragun, and Igor M. Sauer.

In order to stimulate excellent and creative research ideas that might take regenerative therapies a vital step forward, the Einstein Center offers a special two-stage funding scheme. At first, the Kickbox seed grant provides a great framework to investigate initial ideas and to develop sound research concepts. Subsequently, the flexible funds enable the realisation of projects that evolved from the Kickbox initiation phase in order to reach the scientific goals of the Einstein Center. Congratulations!
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ECRT Kickbox - Junior Scientist Grant
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Karl Hillebrandt receives one of the 2017 Einstein Center for Regenerative Therapies (ECRT) Kickbox – Junior Scientist Grant. The project is entitled "Fighting liver cirrhosis? Establishment and analysis of decellularized human cirrhotic liver slices as a 3-dimensional model to study cell matrix interactions".

Liver cirrhosis is one of the main indications for liver transplantation. Due to the organ shortage, this therapy option is limited to the minority of patients suffering from cirrhosis. Therefore, there is a need of alternative treatment options.The aim of our project is to establish a decellularization protocol for human cirrhotic livers slices, which preserves the natural extracellular matrix (ECM) of cirrhotic livers. These decellularized liver slices will serve as a 3 dimensional model to study cell matrix interactions. If we are able to establish a protocol which will preserve the ECM, we will conduct in vitro recellularization experiments to study how the cirrhotic ECM will change the genotype and phenotype of different cell types. With this knowledge we aim to modify specific cell types in vivo or vitro for example prior to cell transplantation. Our ambition is to steer the cell matrix interaction via these modified cells after their transplantation and thereby halt or even reverse the progress of liver cirrhosis. This approach may offer an alternative treatment option in the future.

Team : Karl Hillebrandt, Oliver Klein, Ben Strücker, Igor Sauer  
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SPARK Berlin supports Fikatas Knot
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The Berlin Institute of Health (BIH) and Stiftung Charité teamed up with Stanford University School of Medicine to initiate SPARK Berlin.

We are very pleased to announce that Dr. Panagiotis Fikatas' project “Device for ready-prepared surgical knots” was selected for both, funding and mentorship. 

SPARK was created to overcome the hurdles associated with translating academic discoveries into therapeutics and diagnostics that address unmet medical needs.  The SPARK mission is to help academics overcome the obstacles involved in moving their early discoveries from bench to bedside, to educate faculty, postdoctoral fellows and graduate students on the translational research process and path to clinical application, so that development of promising discoveries becomes second nature to our institution, and to develop more cost-effective and innovative approaches to drug development .

Congratulations!
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Rebeka Major: BIH Promotionsstipendium
Rebeka Major successfully applied for the BIH-Promotionsstipendium grant. Her work will focus in the role of the INDY („I’m Not Dead Yet“) gene in liver regeneration – a project in cooperation with Prof. A. Birkenfeld, Universitätsklinikum Carl Gustav Carus in Dresden.
In the Berlin Institute of Health (BIH), the Max Delbrück Center for Molecular Medicine (MDC) and the Charité - Universitätsmedizin Berlin have joined forces. The core idea is to combine translational research with an overarching systems medicine approach to bridge the gap between basic research and clinical application.
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DFG Research Grant
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Priv.-Doz. Dr. Nathanael Raschzok receives a research grant from the Deutsche Forschungsgemeinschaft (DFG) for his project "Defatting of steatotic liver grafts by normothermic ex vivo machine perfusion with DNP" in collaboration with Prof. Dr. med. Andreas Birkenfeld, Universitätsklinikum Carl Gustav Carus, Dresden.

Transplantation of steatotic marginal liver grafts is associated with a certain risk of graft dysfunction, primary non-function, and biliary complications, which results in a worse outcome compared to transplantation of unimpaired livers.
We hypothesize, that normothermic machine perfusion combined with adequate pharmacological intervention can prevent the deleterious effect of ischemia-reperfusion injury on macrovesicular grafts by a) minimizing the negative effect of cold storage, and by b) actively decreasing the intracellular fat content of the graft.
Mild mitochondrial uncoupling by DNP decreases the intrahepatic fat content of steatotic liver grafts during normothermic ex vivo machine perfusion. Efficient defatting can be safely achieved ex vivo with DNP concentrations that would be toxic in vivo. Systemic side effects of DNP are prevented by exclusive hepatic exposure through machine perfusion, and by washing DNP out of the liver graft at the end of the perfusion period. The synergetic effects of normothermic perfusion and defatting with DNP will prevent ischemia-reperfusion injury and make severely steatotic liver grafts acceptable for transplantation.
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