DFG-funded ExTra Trial
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Prof. Dr. Nathanael Raschzok received a grant of € 1.85 million for the first three years from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) for the Pilot, open, prospective, randomized, multicenter trial on expanding the donor pool by quality assessment of liver grafts declined for transplantation by normothermic ex vivo liver perfusion – ExTra. Co-applicants and/or significantly involved in the preparation of the study were Prof. Dr. Johann Pratschke, Prof. Dr. Igor M. Sauer, Prof. Dr. Dominik Modest, and Priv.-Doz. Dr. Simon Moosburner.

Liver transplantation in Germany is severely limited by a critical shortage of acceptable grafts and a high mortality rate on the waiting list. Furthermore, a significant number of organs are declined due to quality concerns. As demonstrated in pilot studies in the UK, Netherlands, Australia, and the United States, declined liver grafts can and should be used for transplantation after quality assessment by normothermic ex vivo liver machine perfusion (NMP).

The ExTra trial is a randomized controlled trial with a specific focus on patients with a model for end-stage liver disease (MELD) score ≤25 that are not eligible for (non)standard MELD exceptions. This cohort of patients faces an unacceptably long wait time for transplantation, which increases their mortality risk while on the waitlist. The ExTra trial aims to demonstrate that the time-to-transplant for these patients is shortened through the use of grafts that were initially declined for transplantation but fulfill specified quality criteria on normothermic ex vivo machine perfusion assessment. A total of 186 patients will be randomized in a 1:1 fashion to the experimental arm, which consists of a 12-month option to receive a liver graft that was declined by all German transplant centers but meets specified quality criteria, in addition to listing for liver transplantation through the standard allocation process. The control arm will consist of patients who are waitlisted for liver transplantation through the standard allocation process. Liver grafts that have been declined for transplantation must meet specific quality criteria. These include a maximum of 60% macrovesicular steatosis, no fibrosis greater than stage F3, and no cirrhosis. In line with previously published viability criteria for initially declined liver grafts, the decision to use or decline the graft will be made at least four hours after the start of perfusion.

The ExTra trial aims to show that by expanding the donor pool to include the ExTra option of non-transplantable organs, which appear to be usable after machine perfusion, patients without a high MELD score can be transplanted significantly faster. The ExTra trial is thus the first study worldwide in which this concept will be investigated in a randomized clinical trial. The study should make an important contribution to expanding the donor pool for liver transplants and thus ultimately help all patients on the waiting list for liver transplantation.

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New DFG research group FOR 5628 with our participation
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The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) is establishing eight new research groups. One of these groups is FOR 5628: "Multiscale magnetic resonance elastography in cancer: The mechanical niche of tumor formation and metastatic spread – towards an improved diagnosis of cancer through mechanical imaging". The speaker and initiator is Prof. Ingolf Sack.

During the development of a tumour, the tissue changes its shape, e.g., alternating between hard and fluidic states. For this, cells exert forces and are simultaneously influenced by forces. This research group is investigating which mechanical-physical processes are behind this. How do tumours and metastases develop? What makes them resistant to therapy? The team is investigating these questions using magnetic resonance elastography (MRE) – a new clinical procedure that can be used to record the mechanical properties of body tissue. The goal is to be able to better diagnose tumours.
Dr. Karl Hillebrandt and Prof. Dr. Igor Sauer are part of the research group as PI in three projects:
  • A03 Cancer cell unjamming and jamming as prerequisites for the formation of primary and metastatic tumors
  • B03 Scaffold composition and fluid pressure in recellularized hepatic and pancreatic tumors
  • C01 Multiscale mechanical properties of tumors and tumor environment – from tissue specimens to patients

Was are happy to be part of this exzellent team!
ECRT Consumable Grant - Advanced Scientists
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Nils Haep successfully applied for funding from the ECRT Consumable Grant - Advanced Scientists. In his project, Nils is investigating the function of a cysteine-type endopeptidase and described mutations in the endopeptidase in induced pluripotent stem cell derived hepatocytes and their influence on Adiponutrin induced NAFLD.

Congratulations!
science x media Tandem Program: "From Slices to Spaces"
Prof. Dr. Moritz Queisner and Frédéric Eyl (Designer and Managing Director of TheGreenEyl) successfully applied to the Stiftung Charité for funding as a "science x media tandem".
The science x media tandems are the first programme in the new funding priority "Open Life Science". With this funding priority, the Charité Foundation is working to make the life sciences in Berlin more comprehensible and accessible to a broader public and to strengthen the trustworthiness of medical professionals.

Under the title "From Slices to Spaces", the tandem of Moritz Queisner and Frédéric Eyl is implementing a science parcours in which spatially complex research data from surgery and biomedicine will be made multisensually accessible to a broad audience through new visualization techniques. Building on research work on new imaging techniques by Moritz Queisner, they employ Extended Reality techniques. Due to their unique ability to link digital objects with the real environment of the viewers, the 4D images they generate are particularly suited for representing and conveying spatial information.

This is where the tandem's project comes in: 4D images are not only interesting for researchers to understand complex research data but can also provide laypeople with a less presupposing insight into research data and processes. Frédéric Eyl's media expertise will be used to make the specific visual knowledge from research comprehensible and experiential for non-experts. The science parcours is intended to integrate as a digital extension into the architecture of the new research building, "Der Simulierte Mensch", located on the premises of Charité. The parcours will include the facade, the inter-floor airspace, and the central glass surfaces within the building as its stations. By enabling users to explore 4D research data within the architecture and investigate it using their own smartphones in an AR application, concrete practices and deployment locations of new image-based technologies become experiential and comprehensible. This project not only enhances the perception of Charité and the scientific location of Berlin but also opens up places of knowledge creation to the public, making practices and techniques of life sciences more visible.


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Eriselda Keshi and Simon Moosburner CSP fellows
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Dr. Eriselda Keshi and Dr. Simon Moosburner successfully applied for the BIH Charité Clinician Scientist Program (CSP).
The program provides a unique opportunity for young medical doc- tors to combine their clinical training with protected time for research. This structured career path fosters translation of scientific discoveries into application and strengthens the innovative capacity of academic medicine.
Participants of the CSP devote 50 percent of their working hours to research over a period of three years.

Dr. Keshi will work on "NeoPancreasPrint, a 3D printed islet hosting tissue based on biocompatible ink derived from human decellularized pancreas".
Dr. Moosburner applied with this project "Alleviation of Senescence induced Ischemia-Reperfusion in Liver Grafts of Elderly Donors [SenEx".



Congratulations!
DFG | Grant for Machine Perfusion RCT
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The German Research Foundation (Deutsche Forschungsgemeinschaft – DFG) s sponsoring a multicenter randomized controlled clinical trial by Prof. Dr. Georg Lurje entitled "End-ischemic hypothermic oxygenated (HOPE) or normothermic machine perfusion (NMP) compared to conventional cold storage (CCS) in donation after brain death (DBD) liver transplantation; a prospective multicenter randomized controlled trial (HOPE-NMP)".

The purpose of this study is to test the effects of end-ischemic NMP versus end-ischemic HOPE technique in a multicentre prospective randomized controlled clinical trial (RCT) on ECD liver grafts in DBD liver-transplantation (HOPE-NMP). Two-hundred-thirteen (n = 213) human whole organ liver grafts will be submitted to either NMP (n = 85) or HOPE (n = 85) directly before implantation and going to be compared to a control-group of patients (n = 43) transplanted with static cold storage preserved ECD-allografts. Primary (surgical complications as assessed by the comprehensive complication index [CCI]) and secondary (graft- and patient survival, hospital costs, hospital stay) endpoints are going to be analysed.


Congratulations !
BIH Medical Student Research Stipend for Cao Zhong Jing Jin
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Cao Zhong Jing Jin under the supervision of Dr. med. Matthäus Felsenstein successfully applied for the BIH Medical Student Research Stipend on their project “Deciphering the molecular determinants for the transformation of high-grade pancreatic duct dysplasia to invasive carcinoma by single-cell transcriptomics”. She is conducting a cutting-edge research project merging molecular data with histological information in collaboration with the BIH core facilities for single-cell genomics (Dr. Thomas Conrad) and intelligent imaging (Prof. Dr. Christian Conrad). Using modern single-cell- and spatial transcriptomics on pancreatic precursor and carcinoma samples, the project aims at defining molecular signatures that drive dysplastic cells.

Congratulations!
New DFG project "4D Imaging"
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The DFG Schwerpunktprogramm „Das Digitale Bild“ (SPP 2172) funds the new project “4D Imaging: From Image Theory to Imaging Practice” (2023-2026). Principal investigators are Prof. Dr. Kathrin Friedrich (Universität Bonn) and Prof. Dr. Moritz Queisner.

The term 4D imaging refers to a new form of digital visuality in which image, action and space are inextricably interwoven. 4D technologies capture, process and transmit information about physical space and make it computable in real time. Changes due to movements and actions become calculable in real time, making 4D images particularly important in aesthetic and operational contexts where they reconceptualize various forms of human-computer interaction. The 4D Imaging project responds to the growing need in medicine to understand, use, and design these complex imaging techniques. It transfers critical reflexive knowledge from research into clinical practices to enable surgeons to use and apply 4D Imaging techniques. Especially in surgical planning, 4D Imaging techniques may improve the understanding and accessibility of spatially complex anatomical structures. To this end, the project is developing approaches to how 4D imaging can complement and transform established topographic ("2D") imaging practices.

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EKFS grant for functional role and clinical relevance of ecDNA in pancreatic adenocarcinoma
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Dr. Matthäus Felsenstein successfully applied for funding from the Else Kröner Fresenius Stiftung (EKFS) for his project “The functional role and clinical relevance of extrachromosomal DNA (ecDNA) in pancreatic adenocarcinoma”. In close collaboration with the excellence group around Professor Anton Henssen, he is aiming at improved understanding of unique genomic patterns as a results of complex chromosomal rearrangements in pancreatic adenocarcinoma that could drive its aggressive behavior. He will use state-of-the art three-dimensional tissue culture to enrich for neoplastic cells from primary PDAC specimen and subsequently perform genome analyses to identify samples that harbor extrachromosomal DNA. The clinical impact of these chromosomal structures will be explored by clinical correlation analyses and therapy response in vitro.

Congratulations!
"Einstein Kickbox - Advanced Scientists" grant
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Nils Haep successfully applied for the "Einstein Kickbox - Advanced Scientists" grant of the Einstein Center for Regenerative Therapies (ECRT). The purpose of the grant is to provide start-up funding for interesting experimental projects in regenerative medicine.  In his project, Nils is investigating the function of a cysteine-type endopeptidase and described mutations in the endopeptidase in hepatocytes using live-cell imaging and metabolomics. Through this preliminary work, he hopes to generate a hypothesis on the function of the endopeptidase and the underlying mechanism of the mutations. In the next step, he plans to develop a disease model for fatty liver from induced pluripotent stem cells.
BMBF funds KIARA
With the programme "AI-based assistance systems for process-accompanying health applications", the Federal Ministry of Education and Research (BMBF) is funding innovative research and development work on interactive assistance systems that support processes in clinical health care using artificial intelligence methods.

Together with the partners Gebrüder Martin GmbH & Co. KG, Tuttlingen, HFC Human-Factors-Consult GmbH, Berlin and the Fraunhofer Institute for Telecommunications Heinrich-Hertz-Institut (HHI), Berlin, we successfully applied with the project "AI-based recording of work processes in the operating theatre for the automated compilation of the operating theatre report" (KIARA).


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Operating theatre reports document all relevant information during surgical interventions. They serve to ensure therapeutic safety and accountability and as proof of performance. The preparation of the OR report is time-consuming and ties up valuable working time – time that is then not available for the treatment of patients.

In the KIARA project, we are working on a system that automatically drafts operating theatre reports. The KIARA system is intended to relieve medical staff: it documents operating theatre activities and creates a draft of the report, which then only needs to be checked, completed and approved. The system works via cameras integrated into operating theatre lamps. Their image data is then analysed with the help of artificial intelligence to recognise and record objects, people and all operating theatre activities. The ambitious system is to be developed and tested in a user-centred manner for procedures in the abdominal cavity and in oral and maxillofacial surgery.

KIARA is intended to continuously learn through human feedback and to simplify clinical processes for the benefit of medical staff by automating the creation of operating theatre reports. The system can also be applied to other operating theatre areas in the future.

The project has a financial volume of € 2.16 million.
The kick-off meeting took place on 16.09.2022 at the Charité.
DFG Walter-Benjamin grant for the investigation of sex as a biological variable in alloimmunity
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With a DFG Walter-Benjamin grant Dr. med. Friederike Martin will join the laboratory of Transplant Surgery Research at Harvard under the direction of Professor Stefan G. Tullius in Boston to investigate the role of biological sex for transplantation outcome.

Influences of donor and recipient sex on transplantation outcome have been described manifold, as well as an influence of sex hormones on the innate and adaptive immune response. So far, research, investigating the impact of sex hormones and different sex- and age-dependent sex-hormone levels on alloimmune response after solid organ transplantation is lacking. The aim of the project “Sex as a biological Variable in Alloimmunity” is, to delineate the impact of sex hormones and especially estrogens and age-dependent changes in estrogen-levels on alloimmune response after allogenic transplantation.  The project is based on the publication “Recipient sex and estradiol levels affect transplant outcomes in an age-specific fashion” published in the AJT in 2021 by the workgroup of Prof. Tullius.

Friederike, who already received the Sanofi Women in Transplantation fellowship grant for research in gender and sex in transplantation in 2021, will work as a Postdoc on this project in the Tullius Lab for an expected 2 years period, starting in January 2023.


Congratulations!
Detection of nicotinamide adenine dinucleotide (NAD) in cells and blood plasma
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Priv,-Doz. Dr. med. Felix Krenzien and Dr. Jennifer Kirwan (Technologieplattform Metabolomik, Max-Delbrück-Centrum für Molekulare Medizin, Berlin) successfully applied for a grant within the Else Kröner Fresenius Stiftung funding line: Translational Research.

Recently, the molecule nicotinamide adenine dinucleotide (NAD) has attracted attention as it is involved in various important regulatory mechanisms, immune signaling, aging and regenerative processes. In this regard, it occupies key positions in many redox reactions of the body due to its role as a redox couple (NAD as an oxidized species and NADH as a reduced species). Consequently, NAD homeostasis (the maintenance of NAD in cells) is considered essential. The scientific consensus for many years was that the oxidized species resides exclusively in the intracellular milieu (iNAD). However, recent findings indicate that NAD also exists extracellularly (eNAD) and it is present in virtually all body fluids (from lymph to saliva to blood plasma). Based on these findings, precursors of NAD have recently been approved by the FDA and are commercially available. Measurement of eNAD in blood plasma is problematic due to its low concentration in the nanomolar range. However, quantifying eNAD plasma levels but also eNAD concentrations in cells is necessary to monitor the intake of NAD or its precursors and to adjust their dosage precisely.
The primary objective of this project is to validate, bioanalyze,and to document the assay for eNAD according to the ICH-M10 guidance document endorsed by the U. S. Food and Drug Administration (FDA). Adherence to the principles presented in this guideline should improve the quality and consistency of bioanalytical data, thereby supporting assay development and market approval. In addition, the assay will also be established for the measurement of intracellular NAD (iNAD), and validation of iNAD quantification will also be performed according to the guideline.

In the second part of the project, a clinical study will be conducted to determine whether the intake of nicotinamide riboside (precursor of NAD) leads to a change in eNAD and iNAD. Thus, the basis for an indication-dependent bioanalysis of the measurement of NAD will be developed to monitor the intake of NAD and its precursor or to adjust the dosage specifically on the basis of the quantification.
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DFG Funds Extension of the Digital Clinician Scientist Program
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Following the successful application for approval of the continuation of the BIH Charité Digital Clinician Scientist Program (DCSP) by the DFG, additional funding of around 1.3 million euros is now available over a period of two years: The DFG funding benefits physicians at Charité who have embarked on a scientific medical career path and, with their innovative research projects, are already playing a key role in shaping the digital transformation of healthcare during their residency training.

The Digital Clinician Scientist Program (DCSP) was jointly initiated by the German Research Foundation (DFG), the BIH, and the faculty of Charité - Universitätsmedizin Berlin in early 2019. The DCSP is an extension of the successful BIH Charité Clinician Scientist Program, which has set standards in the medical research landscape throughout Germany. The structured career path enables researching physicians to build the foundation for a successful career as a clinician scientist by providing protected time for research activities and non-clinical training during their residency. The DCSP is intended for clinically active physicians who are already actively shaping the digital transformation process of healthcare with their innovative research projects during their residency training. The main applicant of the continuation application is Prof. Dr. Igor M. Sauer, Director of the BIH Charité Digital Clinician Scientist Program, Deputy Clinic Director of the Department of Surgery, and Head of the Experimental Surgery at Charité. Since the start of the program in 2019, 24 physicians have benefited from funding, thus a broad spectrum of digital topics is already being addressed in various clinics at the Charité. The DFG originally funded the program for three years with more than three million euros. With the approved extension, the funding program now has a further 1.3 million euros available over a period of two years.
Development of human-based hydrogels as a substitute for mouse-derived Matrigel for cancer research
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With a new funding line, Charité 3R wants to support the development of animal-free cell cultures at Charité.

For in vitro cancer research, mini-tumours are grown in a gel-like cultivation structure that serves the three-dimensional growth of the mini-tumours. This gel-like cultivation substance is obtained from mouse tumours, an unnatural cultivation environment for human mini-tumours. The aim of the project "Development of human-based hydrogels as a substitute for mouse-derived Matrigel for cancer research" by Björn Papke from the Institute of Pathology and Karl Hillebrandt is to produce a cultivation structure without animal additives. For this purpose, a cultivation structure, also gel-like, is to be produced from tissue obtained from patients during surgical procedures, which better corresponds to the natural environment of the human mini-tumours.


Congratulations!
BMBF grant – GreifbAR
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The Federal Ministry of Education and Research (BMBF) funds the project "Tangible reality - skilful interaction of user hands and fingers with real tools in mixed reality worlds (GreifbAR)" – a cooperation of the Augmented Vision group of the DFKI (Prof. Dr. Didier Stricker), the Department of Psychology and Human-Machine Interaction of the University of Passau (Prof. Dr. Susanne Mayr), the company NMY Mixed Reality Communication (Christoph Lenk), and the Experimental Surgery of Charité – Universitätsmedizin Berlin (Prof. Dr. Igor M. Sauer).

The goal of the GreifbAR project is to make extended reality (XR) worlds, including virtual (VR) and mixed reality (MR), tangible and graspable by allowing users to interact with real and virtual objects with their bare hands. Hand accuracy and dexterity is paramount for performing precise tasks in many fields, but the capture of hand-object interaction in current XR systems is woefully inadequate. Current systems rely on hand-held controllers or capture devices that are limited to hand gestures without contact with real objects. GreifbAR solves this limitation by proposing a sensing system that detects both the full hand grip including hand surface and object pose when users interact with real objects or tools. This sensing system will be integrated into a mixed reality training simulator.

Competent handling of instruments and suture material is the basis of every surgical activity. The main instruments used in surgery are in the hands of the surgical staff. Their work is characterised by the targeted use of a large number of instruments that have to be operated and controlled in different ways. Until now, surgical knotting techniques have been learned by means of personal instruction by experienced surgeons, blackboard images and video-based tutorials. A training and teaching concept based on the acquisition of finger movement does not yet exist in surgical education and training. Learning surgical account techniques through participant observation and direct instruction by experienced surgeons is cost-intensive and hardly scalable. This type of training is increasingly reaching its limits in daily clinical practice, which can be attributed in particular to the changed economic, social and regulatory conditions in surgical practice. Students and trainees as well as specialist staff in further training are therefore faced with the problem of applying and practising acquired theoretical knowledge in a practice-oriented manner. Text- and image-based media allow scalable theoretical knowledge acquisition independent of time and place. However, gestures and work steps can only be passively observed and subsequently imitated. Moreover, the learning success cannot be quantitatively measured and verified.

The aim of the Charité's sub-project is therefore to develop a surgical application scenario for Mixed/Augmented Reality (MR/AR) for the spatial guidance and verifying recording of complex fine motor finger movements for the creation of surgical knots, the practical implementation and technical testing of the developed concept within the framework of a demonstrator, and the evaluation of the usability of the system for use in a clinical context.
Two new research grants by Berliner Krebsgesellschaft
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The Berliner Krebsgesellschaft will fund two very interesting research projects by Dr. Linda Feldbrügge and Dr. Karl Hillebrandt in collaboration with Dr. Björn Papke.

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„Purinergic immune regulation in peritoneal metastases of gastric cancer via CD39 and ENTPD3 – target for a novel immune Checkpoint inhibition?“ – PI: Dr. Linda Feldbrügge

Peritoneal metastasis, especially derived from gastric cancer (GC), has a poor prognosis with a median survival of only months. Treatment is usually confined to palliative systemic chemotherapy, complemented individually by checkpoint inhibitors that block PD1-signaling. Innovative therapies combining surgery with local drug application such as hyperthermic intraperitoneal chemotherapy (HIPEC) or pressurized intraperitoneal aerosol chemotherapy (PIPAC) are still pending confirmation in clinical trials. Purinergic signaling, which involves ATP hydrolysis and generation of adenosine, regulated through CD39 (ENTPD1) and related enzymes, has been recognized as a critical immunoregulatory pathway in the tumor microenvironment (TME). The objective of the current project is to characterize the immune environment in the unique setting of peritoneal metastasis of gastric cancer with a focus on ectonucleotidases CD39 and ENTPD3 on T cells, macrophages and MDSC as well as mechanisms of ectonucleotidase-mediated immune regulation in tumor associated macrophages in vitro. As a high-volume center for surgical therapy of peritoneal malignancies and with years of experience in ectonucleotidase research, we aim to advance the understanding of peritoneal metastasis and contribute to improving treatment options for our patients.

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"The influence of decellularised tumour matrix heterogeneity in relation to KRAS/MAPK inhibition of in vitro colorectal liver metastases." PI: Dr. Karl Hillebrandt and Dr. Björn Papke (Dept. of Pathology)

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide, with approximately 900,000 annual deaths. 30-50% of patients develop colorectal liver metastases (CRLM) during their disease. More than 50% of these tumors have mutations in the KRAS oncogene, making them usually poorly treatable. Despite multimodal therapy concepts have improved the outcome of these patients, a large proportion of patients suffer a recurrence of their disease. For better therapeutic concepts, we need to better understand the tumor biology and metastatic mechanisms of these diseases. In vitro models, such as two-dimensional cell culture, are primarily used for this purpose. These models can only reflect the physiological complexity to a limited extent. Recently, it was shown that the use of organ-specific and tumor-specific extracellular matrix (ECM) has an impact on the behavior of human CRC cell lines. Culture of cell lines with decellularized matrix resulted in cells adopting a metastatic cell state and forming significantly more metastases in a mouse model than cells cultured on plastic or collagen. The goal of our project is to study the growth (with and without inhibition of the RAS/MAPK signaling pathway) of patient-derived tumor organoids growing on different decellularized metastatic matrices (dMM) and decellularized liver matrices (dLM). These studies of tumor matrix heterogeneity are essential to define which starting materials, for in vitro modeling of our three-dimensional tumor organoid culture, can be used to develop the most physiological, personalized dLM/dMM-based CRLM in vitro model possible. Based on these results, we plan to conduct small-scale therapy evaluations for personalized tumor therapy using our in vitro dLM/dMM-based CRLM in the near future.

Congratulations!
ADBoard | Therapeutic Assist and Decision Algorithms for Hepatobiliary Tumor Boards
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The Gemeinsamer Bundesausschuss (Federal Joint Committee, G-BA) will fund a new collaborative project of the Charité's Dept. of Surgery and the Deutsches Forschungszentrum für Künstliche Intelligenz (German Research Center for Artificial Intelligence, DFKI), Speech and Language Technology.

The aim of the project Therapeutic Assist and Decision Algorithms for Hepatobiliary Tumor Boards (ADBoard) is the validation and evaluation of decision support systems based on linguistic and semantic methods of artificial intelligence (AI) for interdisciplinary tumour conferences in the care of tumour patients. Natural language processing (NLP) and machine learning (ML) will provide the technical basis for data extraction, data filtration and decision support for the automated generation of therapy recommendations. Interdisciplinary tumour board conferences are medical conferences, usually held on a weekly basis, which are required by the respective medical societies to determine a therapy or monitoring plan for patients with malignant diseases. Participants are representatives of the required medical disciplines who, taking into account the tumour characteristics and the general health of the patient, review the treatment options and make a therapy recommendation.

The Gemeinsamer Budesausschuss (Federal Joint Committee, G-BA) has the mandate to promote new forms of health care that go beyond the current standard provision of statutory health insurance, and health care research projects that are aimed at gaining knowledge to improve existing health care.

ADBoard is a collaboration of Priv.-Doz. Dr. Felix Krenzien, Priv.-Doz. Dr. Christian Benzing, Prof. Dr. Dominik Modest, Prof. Dr. Johann Pratschke (Charité – Universitätsmedizin Berlin) and Prof. Dr.-Ing. Sebastian Möller, Head of Research Department Speech and Language Technology, German Research Center for Artificial Intelligence.
Advanced Clinician Scientists
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Priv.-Doz. Dr. Nathanael Raschzok and Priv.-Doz. Dr. Felix Krenzien successfully applied for the BIH Charité Advanced Clinician Scientist Pilot Programme (AdCSP) in a highly competitive process.

The BIH Charité AdCSP is designed as a career-phase-specific, sustainable funding programme that aims to closely interlink individual and institutional funding. The primary goal of the programme is to simultaneously incentivise the fellows and recognise the permissive academic culture of the respective clinics or institutes. Like the BIH Charité Clinician Scientist Programme (CSP) and the "Digital Clinician Scientist Programme" (DCSP), which has been additionally funded by the DFG since 2019, it is intended to be open to all clinical disciplines and to offer multiple networking opportunities for the funded fellows and participating clinics and institutes.

Congratulations!
Grant provided by the Berliner Krebsgesellschaft e.V.
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Dr. med. M. Felsenstein receives a grant provided by the Berliner Krebsgesellschaft e.V. for his project "Deciphering the molecular determinants of pancreatic duct dysplasia by analysis of single-cell transcriptomics (RNAseq) in precursor lesions".

Besides great advances in the molecular and genetic understanding of pancreatic duct adenocarcinoma (PDAC), this tumor entity remains particularly aggressive with dismal prognosis. Recent single-cell sequencing studies underline the eminent urgency to understand tumor heterogeneity in the setting of PDAC. More detailed knowledge about the molecular mechanisms of pancreatic cancer evolution, carcinogenesis and heterogeneity could direct ideas for earlier detection and more effective targeted therapies, also preventing disease recurrence. Future therapeutic approaches in precision medicine will likely focus on the disease relevant sub-populations, specifically driving cancer progression, dissemination and exerting tumor escape mechanisms. In-depth transcriptomic data of single carcinoma environmental cells and respective cell clusters may help to discover novel biomarkers, which can be clinically instrumented for earlier detection and putatively increase the fraction of patients, amenable to curatively intended therapies. This study aims to analyze sorted single cells of macro-dissected precursor and cancerous lesions of the pancreas by single nuclei RNA sequencing (snRNAseq). In this feasibility study, we will include 10 patients, who will undergo resection of the pancreas due to “worrisome” or malignant lesions. We will perform in-depth transcriptomic analysis of pancreatic dysplasia in order to broaden our understanding of the molecular mechanisms of pancreatic carcinogenesis.

Congratulations!
Karl Hillebrandt | Charité 3R Tandem project for early career researchers
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Together with Dr. Björn Papke (Molecular tumour pathology), Dr. Karl Hillebrandt was able to acquire funding for a "Tandem project for early career researchers" from the Charité 3R. The project is entitled "A personalised therapy approach implementing individually matched matrix-based in vitro colorectal liver metastases to reduce metastatic mouse models".
Although modern multimodal therapy strategies have improved the clinical outcome of patients with colorectal liver metastases (CRLM), the overall prognosis is still poor. To further improve treatment options for patients, it is necessary to develop and test new targeted therapeutic approaches. To date, mouse models have often been used to study metastatic colorectal cancer. However, the rate of successful translation of animal models into clinical trials is less than 8%, highlighting the urgent need for alternative models to study the biology of metastatic cancer. This project aims to develop a novel personalised extracellular matrix-based in vitro model of human CRLM. This model will be validated against existing data from patient-derived organoids and xenografts (histology, single cell RNA sequencing and targeted gene sequencing). After internal comparison of our in vitro CRLM with the original CRLM, we will translate it into a personalised drug screening platform to test drug response from standard therapy to novel inhibitor combinations.
Two new (Junior) Clinician Scientitsts
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Dr. Simon Moosburner and Dr. Tomasz Dziodzio successfully applied for the BIH Charité (Junior) Clinician Scientist Program.

Dr. Dziodzio is studying pathomechanisms of obesity in the context of kidney transplantation and investigates the impact of obesity on the immune response in the kidney transplant recipient. In addition, a clinical trial will investigate whether surgical weight reduction in obese patients prior to kidney transplantation leads to improved graft function.

Dr. Moosburner is working on the extracorporeal evaluation of liver grafts from older donors. The aim is to characterise old liver grafts during normothermic machine perfusion. For this purpose, a model for normothermic ex vivo machine perfusion of small animal livers as well as liver transplantation in the rat model was established.

CASSANDRA | Clinical ASSist AND aleRt Algorithms
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The Innovationsausschuss beim Gemeinsamen Bundesausschuss (G-BA) is funding 33 new projects in healthcare research. A total of 186 project applications were received in response to the funding announcements of December 2019. Nine project proposals from the open topic area and 24 project proposals from the topic-specific area received a positive funding decision.

Our project CASSANDRA (Clinical ASSist AND aleRt Algorithms – Early detection of postoperative complications with machine learning algorithms) is one of the projects funded for three years.

The aim of the project is to evaluate Machine Learning (ML) in the detection of postoperative complications after major abdominal surgery. By means of digital records and ML-driven analysis of perioperative risk factors, postoperative parameters as well as telemedical vital parameter monitoring, it is to be examined whether complications requiring treatment – in particular infections of the abdominal cavity after liver, pancreas, stomach and intestinal surgery – can be automatically detected and predicted, in order to develop the basis for an autonomous real-time monitoring system on normal wards.
CASSANDRA is a collaboration of Axel Winter, Dr. Max Maurer, Prof. Dr. Igor M. Sauer (Charité – Universitätsmedizin Berlin) and Prof. Dr. Bert Arnrich, Head of the Chair, Professor for Digital Health - Connected Healthcare, Hasso Plattner Institut.
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