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B06 - The role of programmed cell death in mitochondrial hepatopathy

Hamid Kashkar
CECAD Research Center/Institute for Medical Microbiology, Immunology and Hygiene (IMMIH), University Hospital Cologne

E-mail: H.KashkarSpamProtectionuni-koeln.de
Phone: +49 - 221 / 478 84091
For more information and contact please visit the KASHKAR LAB.

Mitochondrial dysfunction result in tissue degeneration; frequently associated with elevated apoptosis within the affected tissues. However, whether and how apoptosis interferes with disease pathogenesis is still not determined. The central objective of this project is to mechanistically determine the role of apoptosis in tissue damage upon mitochondrial dysfunction by employing a model for mitochondrial hepatopathy. This knowledge will expand our view about the pathophysiology of mitochondrial diseases and will drive the development of therapeutically relevant agents that interfere with the dynamic interconnection between cell death and mitochondrial dysfunction.

Latest publications
Habich, M., Salscheider, S.L., Murschall, L.M., Hoehne, M.N., Fischer, M., Schorn, F., Petrungaro, C., Ali, M., Erdogan, A.J., Abou-Eid, S., Kashkar, H., Dengjel, J., and Riemer, J. (2019). Vectorial import via a metastable disulfide-linked complex allows for a quality control step and import by the mitochondrial disulfide relay. Cell Rep. 26, 759-774.

Schiffmann, L.M., Fritsch, M., Gebauer, F., Günther, S.D., Stair, N.R., Seeger, J.M., Thangarajah, F., Dieplinger, G., Bludau, M., Alakus, H., Göbel, H., Quaas, A., Zander, T., Hilberg, F., Bruns, C.J., Kashkar, H., and Coutelle, O. (2019). Tumour-infiltrating neutrophils counteract anti-VEGF therapy in metastatic colorectal cancer. Br. J. Cancer 120, 69-78.

Chauhan, D., Bartok, E., Gaidt, M.M., Bock, F.J., Herrmann, J., Seeger, J.M., Broz, P., Beckmann, R., Kashkar, H., Tait, S.W.G., Müller, R., and Hornung, V. (2018). BAX/BAK-Induced Apoptosis Results in Caspase-8-Dependent IL-1β Maturation in Macrophages. Cell Rep. 25, 2354-2368.

Saita, S., Nolte, H., Fiedler, K.U., Kashkar, H., Venne, A.S., Zahedi, R.P., Krüger, M., and Langer, T. (2017). PARL mediates Smac proteolytic maturation in mitochondria to promote apoptosis. Nat Cell Biol. 19, 318-328.

Schiffmann, L.M., Brunold, M., Liwschitz, M., Goede, V., Loges, S., Wroblewski, M., Quaas, A., Alakus, H., Stippel, D., Bruns, C.J., Hallek, M., Kashkar, H., Hacker, U.T., Coutelle, O. (2017). A combination of low-dose bevacizumab and imatinib enhances vascular normalisation without inducing extracellular matrix deposition. Br. J. Cancer. 116, 600-608.

Knittel, G., Liedgens, P., Korovkina, D., Seeger, J. M., Al-Baldawi, Y., Al-Maarri, M., Fritz, C., Vlantis, K., Bezhanova, S., Scheel, A. H., Wolz, O. O., Reimann, M., Möller, P., López, C., Schlesner, M., Lohneis, P., Weber, A. N., Trümper, L., German International Cancer Genome Consortium Molecular Mechanisms in Malignant Lymphoma by Sequencing Project Consortium, Staudt, L. M., Ortmann, M., Pasparakis, M., Siebert, R., Schmitt, C. A., Klatt, A. R., Wunderlich, F. T., Schäfer, S. C., Persigehl, T., Montesinos-Rongen, M., Odenthal, M., Büttner, R., Frenzel, L. P., Kashkar, H., Reinhardt, H. C. (2016). B-cell-specific conditional expression of Myd88p.L252P leads to the development of diffuse large B-cell lymphoma in mice. Blood 127, 2732-41.