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Position for Student Assistant
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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
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Our manuscript "Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants" has been accepted for publication in Frontiers in Immunology, section Alloimmunity and Transplantation. Authors are Muhammad Imtiaz Ashraf, Joerg Mengwasser, Anja Reutzel-Selke, Dietrich Polenz, Kirsten Führer, Steffen Lippert, Peter Tang, Edward Michaelis, Rusan Catar, Johann Pratschke, Christian Witzel, Igor M. Sauer, Stefan G. Tullius, and Barbara Kern.

Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA). Donor antigen presenting cells (APC), particularly dendritic cells (DC), orchestrate early alloimmune responses by activating recipient effector T cells. Employing a targeted approach, we investigated the impact of donor-derived conventional DC (cDC) and APC on the immunogenicity of skin and skin-containing VCA grafts, using mouse models of skin and hind limb transplantation.
By post-transplantation day 6, skin grafts demonstrated severe rejections, characterized by predominance of recipient CD4 T cells. In contrast, hind limb grafts showed moderate rejection, primarily infiltrated by CD8 T cells. While donor depletion of cDC and APC reduced frequencies, maturation, and activation of DC in all analysed tissues of skin transplant recipients, reduction in DC activities was only observed in the spleen of hind limb recipients. Donor cDC and APC depletion did not impact all lymphocyte compartments but significantly affected CD8 T cells and activated CD4 T in lymph nodes of skin recipients. Moreover, both donor APC and cDC depletion attenuated the Th17 immune response, evident by significantly reduced Th17 (CD4+IL-17+) cells in the spleen of skin recipients and reduced levels of IL-17E and lymphotoxin-α in the serum samples of both skin and hind limb recipients. In conclusion, our findings underscore the highly immunogenic nature of skin component in VCA. The depletion of donor APC and cDC mitigates the immunogenicity of skin grafts while exerting minimal impact on VCA.

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