Project: This project aims to analyse purinergic signal pathways, especially ecto-enzymes of the CD39 family and their role in tumor immunology. Tissue expression as well as the activity of the associated purinergic molecules (receptors, signaling molecules and degrading enzymes) will be examined in a patient cohort of different gastrointestinal tumors with and without (peritoneal) metastases.

Methods: Clinical tissue acquisition (perioperative of patients undergoing surgery), FACS, immunohistology, qPCR, cell culture.

Requirements: Medical student with clinical experience with patients (i.e. "Famulaturen") and drawing blood. Above average scientific interest and engagement. Teamwork and self sufficiency.

What we offer: Learning of scientific methods in an excellently equipped laboratory, teamwork. Mentoring in the clinical and lab. Publication of results and potential of a doctoral thesis.

Data: 10h/week. Project duration: 9 months. Begin: November 2021 (flexible). Salary according to TV Stud III for Berlin.

If you're the right person: please send all application documents, e.g. cover letter, curriculum vitae, certificates, attestations, etc. to the following address, quoting the reference number by e-mail to
Charité – Universitätsmedizin Berlin
Chirurgische Klinik, Exp. Chirurgie
z.Hd. Dr. Linda Feldbrügge
Augustenburger Platz 1
D-13353 Berlin
linda.feldbruegge@charite.de

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.

The Berliner Krebsgesellschaft will fund two very interesting research projects by Dr. Linda Feldbrügge and Dr. Karl Hillebrandt in collaboration with Dr. Björn Papke.

"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!

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!

Priv.-Doz. Dr. Nathanael Raschzok and his team are working on strategies for (re-) conditioning of marginal liver grafts by ex vivo liver machine perfusion. The aim for the proposed job offer, which is funded by grants of the Else Kröner-Fresenius-Stiftung, is to make steatotic liver grafts, which are usually discarded from transplantation due to the high risk for the recipient, acceptable for transplantation. We have already established a small animal model of ex vivo liver machine perfusion as well as transplantation. Aim of this project is to test a clinically approved drug in dose-response studies (based on preliminary data), followed by in vivo studies in the rat liver transplantation model.

Your responsibility will be:

• Organ perfusion of murine livers in our established small animal modell for ex vivo liver machine perfusion
• Support of in rat liver transplantation experiments
• Organ recovery and transplantation (not mandatory)
• Biochemical analysis of the perfusat and the lipid metabolism (ELISA), tissue analysis (qRT-PCR, Wester Blot, immunochemistry, immunofluorescence)
• We fully support the application and submission of a doctoral thesis (e.g. Dr. rer.medic or MD/PhD)

Require­ments

• Degree in biology, biochemistry, biotechnology or medicine
• Pevious experience in molecular cell biology and/or proteinbiochemistry, or surgical research
• Proficiency in standard methods, especially histology, immunhistochemistry, qPCR, FACS, microscopy, cell culture/cell isolation
• Excellent english language skills

Personal characteristics

• innovative spirit and extraordinary motivation, interest in purposeful work
• team work orientated
• organized, ability for analytic and independent work ethic

If you're the right person: please send all application documents, e.g. cover letter, curriculum vitae, certificates, attestations, etc. to the following address, quoting the reference number by e-mail to
Charité – Universitätsmedizin Berlin
Chirurgische Klinik, Exp. Chirurgie
z.Hd. PD Dr. Nathanael Raschzok
Augustenburger Platz 1
D-13353 Berlin
nathanael.raschzok@charite.de

The Notch signaling pathway plays an important role both in the development of the ductal systems of the pancreas and the bile ducts as well as in cancer development and progression. The aim of this study was to examine the expression of central proteins of the Notch signaling pathway in pancreatobiliary tumors and its influence on patient survival.

Materials and Methods: We compared the receptors (Notch1, Notch4), activating splicing factors (ADAM17), and target genes (HES1) of the Notch pathway and progenitor cell markers with relevance for the Notch signaling pathway (CD44, MSI1) between pancreatic adenocarcinomas (PDAC, n = 14), intrahepatic cholangiocarcinoma (iCC, n = 24), and extrahepatic cholangiocarcinoma (eCC, n = 22) cholangiocarcinomas.

A significant overexpression of almost all studied components of the Notch signaling pathway can be found in the tumor tissue, however, without a significant influence on patient survival. Therefore, further studies are warranted to draw conclusions on Notch pathway's relevance for patient survival.

The paper "Notch Signaling Pathway in Pancreatobiliary Tumors" is available via Medicina, 2021;57(2):105. Authors are Francesca Borlak, Anja Reutzel-Selke, Anja Schirmeier, Julia Gogolok, Ellen von Hoerschelmann, Igor M Sauer, Johann Pratschke, Marcus Bahra, and Rosa B Schmuck.

We have received the sad news that Professor Duška Dragun, Director of the Biomedical Innovation Academy (BIA) of the Berlin Institute of Health (BIH) and Head of the Charité BIH Clinician Scientist Program, succumbed to her long, severe, bravely endured illness on December 28, 2020 at the age of 51.
 
Her tireless efforts were devoted to her life's work: the Charité BIH Clinician Scientist Program. Ten years ago, she launched the first Clinician Scientist Program in Berlin and over the decade established and continuously expanded it as "best practice" for the German-speaking region. She has played a key role in developing and shaping the various programs for scientifically active physicians: from the Clinician Scientist Program, which enables aspiring specialists to spend up to 50 percent of their working time on research, to the Junior Clinician Scientist Program with 20 percent working time on research, which begins in the first year of specialist training, to the Advanced Clinician Scientist Program for specialists with postdoctoral qualifications. Two years ago, she successfully applied to the German Research Foundation (DFG) for the first and only Digital Clinician Scientist Program in Germany. This enables young physicians and scientists to conduct research and work in the field of digitalization in medicine and healthcare. Thus, within a few years, Duška Dragun made a significant contribution to building a new generation of young professionals for medicine – the impact of her programs will last for a long time, via promising individual careers as well as via the programmatic strengthening of a patient-oriented science.  
 
As a physician herself, Professor Duška Dragun has always been committed to research: As acting senior physician and deputy to the acting director of the Department of Nephrology and Intensive Care Medicine at the Charité Campus Virchow-Klinikum, as well as head of the nephrology research laboratory, she made highly regarded, internationally distinguished contributions to transplantation research with the goal of improving graft approach and long-term survival, preventing cardiovascular comorbidity, and thus improving the quality of life and life expectancy of transplanted patients.  She pursued her great goals with tremendous energy and passion, impressive perseverance and clear determination. She devoted her full attention to her employees, colleagues, and students, being equally attentive, understanding, and demanding.
 
The death of Duška Dragun is a great and painful loss. We will miss her greatly as director of the Charité BIH Clinician Scientist Program, as a physician, university professor and scientist. To us she was an inspiration, a mentor and an ever driving force.

Above all, however, we will greatly miss Duška as a friend.  

Dr. rer. medic. Moritz Queisner received his doctorate certificate today (magna cum laude)! This is in recognition of his work in the field of extended reality technology in visceral surgery. His thesis is entitled XR in surgery – spatial end embodied computing in digital surgery: technology, application, design.

CONGRATULATIONS !

Acta Biomaterialia accepted our latest paper on "Engineering an endothelialized, endocrine Neo-Pancreas: evaluation of islet functionality in an ex vivo model".

Islet-based recellularization of decellularized, repurposed rat livers may form a transplantable Neo-Pancreas. The aim of this study is the establishment of the necessary protocols, the evaluation of the organ structure and the analysis of the islet functionality ex vivo.
After perfusion-based decellularization of rat livers, matrices were repopulated with endothelial cells and mesenchymal stromal cells, incubated for 8 days in a perfusion chamber and finally repopulated on day 9 with intact rodent islets. Integrity and quality of re-endothelialization was assessed by histology and FITC-dextran perfusion assay. Functionality of the islets of Langerhans was determined on day 10 and day 12 via glucose stimulated insulin secretion.
Blood gas analysis variables confirmed the stability of the perfusion cultivation. Histological staining showed that cells formed a monolayer inside the intact vascular structure. These findings were confirmed by electron microscopy. Islets infused via the bile duct could histologically be found in the parenchymal space. Adequate insulin secretion after glucose stimulation after 1-day and 3-day cultivation verified islet viability and functionality after the repopulation process.
We provide the first proof-of-concept for the functionality of islets of Langerhans engrafted in a decellularized rat liver. Furthermore, a re-endothelialization step was implemented to provide implantability. This technique can serve as a bioengineered platform to generate implantable and functional endocrine Neo-Pancreases.

Authors are Hannah Everwien, Eriselda Keshi, Karl H. Hillebrandt, Barbara Ludwig, Marie Weinhart, Peter Tang, Anika S. Beierle, Hendrik Napierala, Joseph MGV Gassner, Nicolai Seiffert, Simon Moosburner, Dominik Geisel, Anja Reutzel-Selke, Benjamin Strücker, Johann Pratschke, Nils Haep, and Igor M. Sauer.

Anna Pfefferkorn won the Best Poster prize for our work on "Molecular and cellular mechanisms of Lipocalin-2 mediated renoprotection in kidney transplantation" at the Kongress für Nephrologie 2020, held in Berlin 1.-4. October, 2020!

Lipocalin-2 (Lcn2) is distinctly upregulated in kidney transplants and serves as an early marker of AKI, DGF and acute rejection. However, the functional role and mechanisms underlying Lcn2 upregulation remain largely unknown. Using a mouse model of kidney transplantation we recently demonstrated a renoprotective role of recombinant Lcn2:Siderophore:Fe (rLcn2). However, the molecular and cellular events underlying the renoprotective effects of rLcn2 in kidney allografts remain unclear. Elucidating these events forms the primary focus of the current study.
rLcn2 significantly lowered CD8+ T cells in the allograft, LN and blood at POD 7, whereas their number remained unaffected in spleen. Nevertheless, the number of CD4+ T Lymphocytes was reduced only in lymph nodes. NKG2D+CD8+T cells and CD27+CD11b+NKp46+NK cells were the most prominent subpopulations of the cytotoxic lymphocytes whose frequencies were significantly reduced in graft, spleen and blood with the treatment of rLcn2. Besides, a significantly reduced infiltration of monocytes/macrophages was also observed at POD-7 with the said treatment. Importantly, degranulation capacity and IFNg production of intragraft and splenic CD4+ and CD8+ T cells were impaired in the treated animals. Besides, rLcn2 lowered hypoxia and reoxygenation induced cytotoxicity of the primary RTECs, associated with reduced caspase-3 cleavage and activation of Erk and AKt signaling.

rLcn2 treatments differentially affects the relative frequencies and activation of various immune cell. Besides, rLcn2 depicts cytoprotective effect on murine primary RTECs during H/R, possibly via activation of Erk and Akt signaling.

CONGRATULATIONS !

Priv.-Doz. Dr. Felix Krenzien received the Ferdinand-Sauerbruch Prize 2020 for his project and publication „The ILLS Laparoscopic Liver Surgery Fellow Skills Curriculum“ published in Annals of Surgery (online ahead of print).

Congratulations!

Laparoscopy is becoming the standard approach in liver surgery. As the degree of difficulty varies greatly from core skills to advanced procedures, strategies for teaching young surgeons need to be reconsidered. We here aimed to design a skills curriculum for LLR. Using the nominal group technique, 22 substeps of LLR were identified by 61 hepatobiliary surgeons. The raters were asked to rate (1) the difficulty of substeps and (2) the minimum number of times that the substep must be performed for mastery of the technique. According to the frequency of defined substeps, being estimated on the basis of high volume center experiences (n = 222 LLR; 1/2017-12/2018), the center's training capacity and defined goals for a 2-year fellowship were calculated.
Ten surgical substeps (45%) are routinely performed and can thus be taught sufficiently at centers carrying out ≥50 LLR in 2 years. As the mobilization of the right liver lobe and the dissection of the hepatic artery or portal vein is performed in only 27% and 28% of all LLR, respectively, sufficient training can only be provided at centers with ≥100 LLRs in 2 years. Mastery of complex parenchymal dissection (19%) and hilar lymphadenectomy (8%) can only be achieved in center performing ≥200 LLR in 2 years.
The authors suggest a stepwise approach for training of hepatobiliary fellows in LLR. Based on the estimated complexity of the substeps and the size of the center, not every substep can be learned within 2 years.

Authors are Felix Krenzien, Wenzel Schöning, Philipp Brunnbauer, Christian Benzing, Robert Öllinger, Matthias Biebl, Marcus Bahra, Nathanael Raschzok, Daniel Cherqui, David Geller, Ho-Seong Han, Go Wakabayashi, Moritz Schmelzle, Johann Pratschke, and the study group of the International Laparoscopic Liver Society (ILLS).

Biomaterials accepted our latest paper on „The Human Liver Matrisome – Proteomic Analysis of Native and Fibrotic Human Liver Extracellular Matrices for Organ Engineering Approaches“.

The production of biomaterials that endow significant morphogenic and microenvironmental cues for the constitution of cell integration and regeneration remains a key challenge in the successful implementation of functional organ replacements. Despite the vast development in the production of biological and architecturally native matrices, the complex compositions and pivotal figures by which the human matrisome mediates many of its essential functions are yet to be defined. Here we present a thorough analysis of the native human liver proteomic landscape using decellularization and defatting protocols to extract create extracellular matrix scaffolds of natural origin that can further be used in both bottom-up and top-down approaches in tissue engineering based organ replacements. Furthermore, by analyzing human liver extracellular matrices in different stages of fibrosis and cirrhosis, we have identified distinct attributes of these tissues that could potentially be exploited therapeutically and thus require further investigation. The general experimental pipeline presented in this study is applicable to any type of tissue and can be widely used for different approaches in regenerative medicine and in the construction of novel biomaterials for organ engineering approaches.

Authors are A. Daneshgar, O. Klein, G. Nebrich, M. Weinhart, P. Tang, A. Arnold, I. Ullah, J. Pohl, S. Moosburner, N. Raschzok, B. Strücker, M. Bahra, J. Pratschke, I.M. Sauer, and K.H. Hillebrandt. The authors acknowledge the support of the Cluster of Excellence Matters of Activity. Image Space Material funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany´s Excellence Strategy – EXC 2025.

„Der Simulierte Mensch“ ("The Simulated Human", Si-M) is a new research building which is currently under construction and is expected to be finished in 2023. The building site is directly adjacent to the Charité Campus Virchow-Klinikum of the Charité - Universitätsmedizin in Berlin-Wedding and is also the birthplace of biotechnology at the TU Berlin.

The initiators of Si-M are Roland Lauster (Head of the Department of Medical Biotechnology at TU Berlin) and Andreas Thiel (Head of the research group Regenerative Immunology and Aging at Charité – Universitätsmedizin Berlin). They applied for the research building in 2018 (GG §91b) and successfully defended it before the German Science Council.

In the building, scientists from both institutions will work together to simulate the functions of human cells and tissues with new technologies of 3D cultivation, multi-organ chips or 3D bioprinting. In contrast to already existing collaborative projects, the building will be used to practice the joint development of models "side by side" in the same laboratory environment. In this way, both the development of organ models and technological developments can be adapted and optimized at the same time.

More information via https://www.si-m.org .

The International Journal of Computer Assisted Radiology and Surgery accepted Christoph Rüger's paper on "Ultrasound in augmented reality: a mixed-methods evaluation of head-mounted displays in image-guided interventions" for publication.

Augmented reality (AR) and head-mounted displays (HMD) are current subjects of investigation in medical practice. A commonly proposed use-case of AR-HMDs is to display data in image-guided interventions. Although technical feasibility has been thoroughly shown, effects of AR-HMDs on interventions are not yet well researched, hampering clinical applicability. Therefore, the goal of this study is to better understand the benefits and limitations of this technology in ultrasound-guided interventions.
We used an AR-HMD system (based on Hololens, Microsoft Corp.) which overlays live ultrasound images spatially correctly at the location of the ultrasound transducer. We chose ultrasound-guided needle placements as a representative task for image-guided interventions. To examine the effects of the AR-HMD, we used mixed methods and conducted two studies in a lab setting: (1) in an experimental study, we asked participants to place needles into a training model and evaluated task duration and accuracy with the AR- HMD as compared to the standard procedure without visual overlay and (2) in a qualitative study, we analysed the user experience with AR-HMD using think-aloud protocols during ultrasound examinations and semi-structured interviews after the task.
Participants (n=20) placed needles more accurately (mean error of 7.4 mm vs. 4.9 mm, p=0.022) but not significantly faster (mean task duration of 74.4 s vs. 66.4 s, p=0.211) with the AR-HMD. All participants in the qualitative study (n=6) reported limitations of and unfamiliarity with the AR-HMD, yet all but one also clearly noted benefits and/or that they would like to test the technology in practice.
We present additional, though still preliminary, evidence that AR-HMDs provide benefits in image-guided procedures. Our data also contribute insights into potential causes underlying the benefits, such as improved spatial perception. Still, more comprehensive studies are needed to ascertain benefits for clinical applications and to clarify underlying mechanisms.

Authors are Christoph Rüger, Markus A. Feufel, Simon Moosburner, Christopher Özbek, Johann Pratschke, and Igor M. Sauer.

F. Claussen, J.M.G.V. Gassner, S. Moosburner, D. Wyrwal, M. Nösser, P. Tang, L. Wegener, J. Pohl, A. Reutzel-Selke, R. Arsenic, J. Pratschke, I.M. Sauer, and N. Raschzok published their trecent work on "Dual versus single vessel normothermic ex vivo perfusion of rat liver grafts using metamizole for vasodilatation" in PLoS One 2020;15(7): e0235635.

Normothermic ex vivo liver perfusion (NEVLP) is a promising strategy to increase the donor pool in liver transplantation. Small animal models are essential to further investigate questions regarding organ preservation and reconditioning by NEVLP. A dual vessel small animal NEVLP (dNEVLP) model was developed using metamizole as a vasodilator and compared to conventional portovenous single vessel NEVLP (sNEVLP).

Livers of male Wistar rats were perfused with erythrocyte-supplemented culture medium for six hours by either dNEVLP via hepatic artery and portal vein or portovenous sNEVLP. dNEVLP was performed either with or without metamizole treatment. Perfusion pressure and flow rates were constantly monitored. Transaminase levels were determined in the perfusate at the start and after three and six hours of perfusion. Bile secretion was monitored and bile LDH and GGT levels were measured hourly. Histopathological analysis was performed using liver and bile duct tissue samples after perfusion.

Hepatic artery pressure was significantly lower in dNEVLP with metamizole administration. Compared to sNEVLP, dNEVLP with metamizole treatment showed higher bile production, lower levels of transaminases during and after perfusion as well as significantly lower necrosis in liver and bile duct tissue. Biochemical markers of bile duct injury showed the same trend.

Our miniaturized dNEVLP system enables normothermic dual vessel rat liver perfusion. The administration of metamizole effectively ameliorates arterial vasospasm allowing for six hours of dNEVLP, with superior outcome compared to sNEVLP.

The Department of Surgery of the Charité (Director: Prof. Dr. Johann Pratschke) at the Charité Center 8 (CharitéCenter for Surgery) invites applications for the position of the Junior Professorship for Digital Surgery and interdisciplinary Technology Research (Salary Group: W1 BBesG-ÜfBE, non-tenured) with the reference number: Prof. 546/2020.

The initial appointment is for three years with the optional extension for another three years follow-ing successful evaluation. It is aimed to turn the Junior Professorship into a W2-Professorship (Salary Group: W2 BBesG-ÜfBE) after six years.The successful candidate has to fulfill the appointment requirements in accordance with § 102a of the Berlin Higher Education Act (Berliner Hochschulgesetz, Gem. § 102a BerlHG) and needs to credibly demonstrate through his/her previous scientific work that he/she is able to fulfill the expectations of the junior professorship.

One of the tasks of this Junior Professorship is the appropriate representation of the research area mentioned above. Within the framework of the Cluster of Excellence Matters of Activity – Image Space Material, he/she is expected to evaluate, accompany and advance the digital transformation in surgery and related disciplines as well as expand the repertoire of methods and initiate innovations. In cooperation with the research areas Cutting and Material Form Function of the Cluster of Excellence, new surgical cutting techniques are to be investigated and developed. It is planned to be linked to the currently being established institutions, The Simulated Human Being (Si-M) and the Berlin Simulation and Training Centre (BeST). In addition to the tasks mentioned, the following three fields of activity are to be covered:

Interdisciplinary Knowledge Transfer

• Implementation of new applications from areas such as deep learning, extended reality (mixed and virtual reality) or robotics in surgical practice requires an intensification of interdisciplinary cooperation
• Continuous exchange between industry and practice as well as with adjacent disciplines (e.g. Radiology)
• Integration of a growing number of applications and competencies from areas outside established medical technology, e.g.game design, computer science or human factor studies

Technology Assessment

• Sustainable implementation of digital technologies through opportunity and risk assessment
• Advising the Department of Surgery on investment decisions through appropriate risk and media competency

Innovation

• Identification of concrete application locations and practices of digital surgery within the clinic and experimental research (e.g. use of technologies in the context of biomedical research approaches to organ replacement as well as oncological models) for future Living Labs and to demonstrate these to the public
• Integration of users, research projects and start-ups also outside the Clinic

The successful candidate will be engaged in teaching activities of the medical education curriculum at Charité, supervise Master and Doctoral candidates, and participate in academic self-organization. In addition, the candidate should present concepts for a good supervision of doctoral students as well as for the integration of his/her research activities into the teaching of the Charité. Appointment requirements are governed by article 102a of the Berlin Higher Education Act (Berliner Hochschulgesetz:§ 102a BerlHG). Completed university degree in Natural Sciences, Humanities and/or Life Sciences or any other related field of Medicine or non-medicine is required. In addition, a Doctorate (Ph.D and/or M.D.) and significant post-doctoral experience are required. Basic medical knowledge is desired.

The Charité is an equal opportunity employer committed to excellence through diversity. As women are under-represented in academics, we explicitly encourage women to send in their application. Women will be given preference over equally qualified men (within the framework of the legal possibilities). We value diversity and therefore welcome all applications – regardless of gender, nationality, social background, religion or age. Equally qualified applicants with disabilities will be given preference.

Written applications according to the format specified on https://career.charite.de/am/calls/application_notes.pdf should be submittedby June 19th, 2020 under https://career.charite.de. For further questions on details, please contact Prof. Dr. Igor Maximilian Sauer.

Pancreatic ductal adenocarcinoma (PDAC) and extrahepatic cholangio-carcinoma (eCC) represent two cancer entities with devastating prognoses. Despite recent progress in research and treatment, therapy remains challenging. Cancer stem cells (CSCs) have been shown to play an important role in metastasis and chemoresistance. Therefore, CSCs may play a promising role as a potential therapeutic target.
A total of 31 patients (23 PDAC, 8 eCC) were included in the study. CSCs were analyzed in a single-cell suspension of tumor samples via fluorescence-activated cell scanning (FACS) with a functional Hoechst 33342 staining as well as a cell surface marker staining of the CSC-panel (CD24, CD44 and EpCAM) and markers to identify fibroblasts, leukocytes and components of the notch signaling pathway. Furthermore, the potential presence of CSCs among primary cancer-associated fibroblasts (CAFs) was assessed using the same FACS-panel.
We showed that CSCs are present in patient-derived dissociated tumor tissue. The functional and surface marker profile of CSC-detection did in fact correlate. The amount of CSCs was significantly correlated with tumor characteristics such as a higher UICC stadium and nodal invasion. CSCs were not restricted to the epithelial cell fraction in tumor tissues, which has been verified in independent analysis of primary cell cultures of CAFs.
Our study confirms the in vivo presence of CSCs in PDAC and eCC, stating a clinical significance thereof and thus their plausibility as therapeutic targets. In addition, stem-like cells also seem to constitute a part of the CAFs.

"Characterization of Pancreatic and Biliary Cancer Stem Cells in Patient-derived Tissue" was published in Anticancer Research. Authors are J. Gogolok, E. Seidel, A. Strönisch, A. Reutzel-Selke, I.M. Sauer, J. Pratschke, M. Bahra, and R.B. Schmuck.

Hepatocyte transplantation (HcTx) is a promising approach for the treatment of metabolic diseases in newborns and children. The most common application route is the portal vein, which is difficult to access in the newborn. Transfemoral access to the splenic artery for HcTx has been evaluated in adults, with trials suggesting hepatocyte translocation from the spleen to the liver with a reduced risk for thromboembolic complications. Using juvenile Göttingen minipigs, we aimed to evaluate feasibility of hepatocyte transplantation by transfemoral splenic artery catheterization, while providing insight on engraftment, translocation, viability, and thromboembolic complications. Four Göttingen Minipigs weighing 5.6 kg to 12.6 kg were infused with human hepatocytes (two infusions per cycle, 1.00E08 cells per kg body weight). Immunosuppression consisted of tacrolimus and prednisolone. The animals were sacrificed directly after cell infusion (n=2), 2 days (n=1), or 14 days after infusion (n=1). The splenic and portal venous blood flow was controlled via color-coded Doppler sonography. Computed tomography was performed on days 6 and 18 after the first infusion. Tissue samples were stained in search of human hepatocytes. Catheter placement was feasible in all cases without procedure-associated complications. Repetitive cell transplantations were possible without serious adverse effects associated with hepatocyte transplantation. Immunohistochemical staining has proven cell relocation to the portal venous system and liver parenchyma. However, cells were neither present in the liver nor the spleen 18 days after HcTx. Immunological analyses showed a response of the adaptive immune system to the human cells. We show that interventional cell application via the femoral artery is feasible in a juvenile large animal model of HcTx. Moreover, cells are able to pass through the spleen to relocate in the liver after splenic artery infusion. Further studies are necessary to compare this approach with umbilical or transhepatic hepatocyte administration.

"Hepatocyte Transplantation to the Liver via the Splenic Artery in a Juvenile Large Animal Model" was published in Cell Transplantation.
Authors are J. Siefert, K.H. Hillebrandt, S. Moosburner, P. Podrabsky, D. Geisel, T. Denecke, J.K. Unger, B. Sawitzki, S. Gül-Klein, S. Lippert, P. Tang, A. Reutzel-Selke, M.H. Morgul, A.W. Reske, S. Kafert-Kasting, W. Rüdinger, J. Oetvoes, J. Pratschke, I.M. Sauer, and N. Raschzok.

Today, Simon Moosburner successfully defended his doctoral thesis entitled "Erweiterung der Spenderpopulation bei Lebertransplantation: Klinischer Bedarf und Entwicklung eines Kleintier-Lebermaschinenperfusionssystems (Expanding the donor pool for liver transplantation: clinical need and development of small animal liver perfusion system)" summa cum laude !

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