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Archiv-Übersicht     Angebot Nr. 14503

Angebotsdatum: 13. April 2022
Art der Stelle: Doktorarbeit
Fachgebiet: Humanmedizin > Immunologie
Titel des Themas: Hypoxia-immune signaling in NK cells during critical illness

Institut: Universitätsmedizin Mannheim, Klinik für Aästhesiologie und Operative Intensivmedizin
Adresse:
PD Holger A. Lindner
Theodor-Kutzer-Ufer 1-3
68167 Mannheim
Tel.: 0621 383 2669   Fax.:
Bundesland: Baden-Württemberg
Homepage: http://https://www.umm.uni-heidelberg.de/grk2727/
E-Mail Kontakt: mail

Beschreibung: Inflammation is associated with development of tissue hypoxia. Failure to resolve inflammatory hypoxia favors immunosuppression as seen in critically ill patients. Inflammatory cytokines initially augment the adaptive hypoxia response in NK cells. We hypothesize that continued hypoxic immune stimulation supports an anti-inflammatory NK cell phenotype. Blood NK cells from critically ill patients with trauma-induced systemic inflammation but not with sepsis are characterized by elevated immune checkpoint protein expression and by impaired immune signaling. The MD project will investigate the contribution of hypoxia-immune signaling interactions to these phenotypic differences in patients admitted to intermediate or intensive care. NK cells from patient blood will be stimulated in vitro and analyzed for immune checkpoints and effector activities by flow cytometry and live cell imaging. We expect this project to provide insight into sepsis pathogenesis towards improved prediction and diagnosis of sepsis in the critically ill.
Methoden: Multicolor-flow cytometry, cell culture, fluorescence microscopy, multiplex assays
Anfangsdatum: 16. Mai 2022
Geschätzte Dauer: 1 Jahr
Bezahlung: Promotionsstipendium
Papers: 1. Coulibaly A, Velásquez SY, Kassner N, Schulte J, Barbarossa MV, Lindner HA. 2021. STAT3 governs the HIF-1α response in IL-15 primed human NK cells Sci Rep. 11(1):7023.

2. Coulibaly A, Bettendorf A, Kostina E, Figueiredo AS, Velásquez SY, Bock HG, Thiel M, Lindner HA, Barbarossa MV. 2019. Interleukin-15 signaling in HIF-1α regulation in natural killer cells, insights through mathematical models. Front Immunol 10:2401.

3. Coulibaly A, Velásquez SY, Sticht C, Figueiredo AS, Himmelhan BS, Schulte J, Sturm T, Centner FS, Schöttler JJ, Thiel M, Lindner HA. 2019. AKIRIN1: A potential new reference gene in human natural killer cells and granulocytes in sepsis. Int J Mol Sci 20(9): 2290.

4. Velásquez SY, Himmelhan BS, Kassner N, Coulibaly A, Schulte J, Brohm K, Lindner HA. 2020. Innate cytokine induced early release of IFNγ and CC chemokines from hypoxic human NK cells is independent of glucose. Cells 9(3):734.

5. Velásquez SY, Killian D, Schulte J, Sticht C, Thiel M, Lindner HA. 2016. Short term hypoxia synergizes with interleukin 15 priming in driving glycolytic gene Transcription and supports human natural killer cell activities. J Biol Chem 291(25):12960-77.
Sonstiges: Please send your application to

Holger.Lindner@medma.uni-heidelberg.de;
grk2727@uni-heidelberg.de

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