Hamid Kashkar

Institute for Molecular Immunology

Prof. Dr. Hamid Kashkar CECAD Cologne
Prof. Dr. Hamid Kashkar

Principal Investigator
Director of Institute for Molecular Immunology

Research Areas

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Cell Death and Immunity

We investigate how cell death impacts on tissue surveillance mechanisms and controls immunity. We aim to explore how alteration of cell death contributes to pathogenesis of human diseases and will exploit this knowledge in therapeutic interventions.

Research Focus

Cell death is a basic biological phenomenon which is fundamental for development and tissue homeostasis. Alterations of cell death processes cause a plethora of diseases and its therapeutic targeting is considered a valuable strategy to treat human diseases. Inhibition of cell death represents one of the hallmarks of cancer and its acceleration has been viewed as the driver of degenerative diseases. Whereas initial studies considered cell death as a quantitative counterbalance of mitosis, it is increasingly evident that dying cells efficiently coordinate the fate of the surrounding tissue by emitting different factors. Different modes of cellular death processes have been identified that involve distinct cellular death machineries and release a battery of different mediators ultimately leading to beneficial or detrimental tissue outcomes. Recent discoveries indicated that different cell death modalities are molecularly interlinked to safeguard the removal of “unwanted” cells, at the same time, the switch to another mode of cell death provokes diverse tissue reactions culminating in distinct phenotypic alterations.

The plasticity of cell death pathways safeguards the efficient removal of “unwanted cells” but can provoke diverse tissue reactions. Cell death can thereby be beneficial or detrimental for the tissues during the course of disease pathogenesis or therapeutic interventions.

Our Goals

Our research focuses on the role of different modes of cell death in the context of human diseases involving the immune system. We aim to exploit this knowledge to design novel therapeutic protocols for cancer, immune disorders, and degenerative diseases. The molecular link between different cellular death modalities and inflammation represents the central objective of our research group.Our results that the therapeutic modalities initially designed to induce cell death also interfere with cellular immune signaling and impact on immunity.

  • We are, in particular, investigating the role of caspases, inhibitor of apoptosis proteins (IAPS) and mitochondria as signalling components that mediate cell death and inflammation. By modelling human diseases in appropriate in vivo model-systems, we will discover the physiological roles of theses processes in tissue homeostasis and their contribution to pathophysiology of human diseases. The molecular knowledge obtained will be exploited to design novel therapeutic protocols for human diseases by targeting cellular death pathways.

Key Publications

  1. Schorn F, Werthenbach JP, Hoffmann M, Daoud M, Stachelscheid J, Schiffmann LM, Hildebrandt X, Lyu SI, Peltzer N, Quaas A, Vucic D, Silke J, Pasparakis M, Kashkar H. (2023) cIAPs control RIPK1 kinase activity-dependent and -independent cell death and tissue inflammation. EMBO J. 42(22):e113614. doi: 10.15252/embj.2023113614
     
  2. Daoud M, Broxtermann PN, Schorn F, Werthenbach JP, Seeger JM, Schiffmann LM, Brinkmann K, Vucic D, Tüting T, Mauch C, Kulms D, Zigrino P, Kashkar H. (2022) XIAP promotes melanoma growth by inducing tumour neutrophil infiltration. EMBO Rep 23(6):e53608 doi: 10.15252/embr.202153608
     
  3. Schiffmann LM, Werthenbach JP, Heintges-Kleinhofer F, Seeger JM, Fritsch M, Günther SD, Willenborg S, Brodesser S, Lucas C, Jüngst C, Albert MC, Schorn F, Witt A, Moraes CT, Bruns CJ, Pasparakis M, Krönke M, Eming SA, Coutelle O, Kashkar H. (2020) Mitochondrial respiration controls neoangiogenesis during wound healing and tumour growth. Nat Commun. 11(1):3653. doi: 10.1038/s41467-020-17472-2
     
  4. Günther SD, Fritsch M, Seeger JM, Schiffmann LM, Snipas SJ, Coutelle M, Kufer TA, Higgins PG, Hornung V, Bernardini ML, Höning S, Krönke M, Salvesen GS, Kashkar H. (2020) Cytosolic Gram-negative bacteria prevent apoptosis by inhibition of effector caspases through lipopolysaccharide. Nat Microbiol. 5(2):354-367. doi: 10.1038/s41564-019-0620-5
     
  5. Fritsch M, Günther SD, Schwarzer R, Albert MC, Schorn F, Werthenbach JP, Schiffmann LM, Stair N, Stocks H, Seeger JM, Lamkanfi M, Krönke M, Pasparakis M, Kashkar H. (2019) Caspase-8 is the molecular switch for apoptosis, necroptosis and pyroptosis. Nature 575(7784):683-687. doi: 10.1038/s41586-019-1770-6
Prof. Dr. Hamid Kashkar CECAD Cologne
Prof. Dr. Hamid Kashkar

Principal Investigator
Director of Institute for Molecular Immunology

Research Areas

1
2
3