Division of Molecular Neurobiology
Prof. Dr. Ana Martin-Villalba
Unraveling the complex functions of CD95 in the central nervous system has been the main focus of our research in the past years. In particular, we discovered the multiple roles played by CD95 in different neural, immune and tumor cells. We have identified the CD95 as a major trigger of cell migration/invasion leading to recruitment of inflammatory cells and tumor progression. On the other side, CD95 crucially contributes to stem cell survival and lineage differentiation. Our current research focus on further characterisation of the role of CD95 in stem cell homeostasis and response to injury; the role of CD95-induced inflammation in neurodegenerative diseases such as Parkinson disease and autoimmune diseases; and the role of CD95 in glioblastoma- and pancreatic adenocarcinoma-derived "cancer stem cells". To dissect CD95‘s biology we combine biochemical and modern genomic technologies as well as cell biology and genetics in human cells and the mouse model systems.
Adult stem cells are found in every organ and are involved in tissue homeostasis and response to injury. More and more molecular players involved in regulation of stem cell homeostasis are recognized as crucial determinants of axonal regeneration and vice versa. Our future research centers on understanding this molecular program, with special focus on the role of CD95/CD95 ligand, Wnt signals and RNA translation/degradation. As an additional level of complexity, we study the modulation of these processes by the immune system. Alteration of the default program controlling stem cell‘s proliferation, survival and differentiation set the ground for tumor initiation. Likewise, interaction of the immune system with the tumor are crucial to tumor progression. Findings from adult stem cells will be further examined in human cancer stem cells and animal models of glioblastoma and pancreatic adenocarcinoma. Our research intends to contribute to the identification of molecular mechanisms involved in stem cell's biology, axonal regeneration and tumor initiation and/or progression.
Letellier, E., Kumar, S., Sancho-Martinez, I., Krauth, S., Funke-Kaiser, A., Laudenklos, S., Konecki, K., Klussmann, S., Corsini, N.S., Kleber, S., Drost, N., Neumann, A., Levi-Strauss, M., Brors, B., Gretz, N., Edler, L., Fischer, C., Hill, O., Thiemann, M., Biglari, B., Karray, S., and Martin-Villalba, A. (2010). CD95-ligand on peripheral myeloid cells activates Syk kinase to trigger their recruitment to the inflammatory site. Immunity 32, 240-252. This article was picked and evaluated by “Faculty of 1000” with a F1000 Factor of 6 http://f1000biology.com/article/id/2629957
Corsini, N., Sancho-Martinez, I., Laudenklos, S., Glagow, D., Kumar, S., Letellier, E., Koch, P., Teodorczyk, M., Kleber, S., Klussmann, S., Wiestler, B., Brüstle, O., Gieffers, C., Hill, O., Thiemann, M., Seedorf, M., Gretz, N., Sprengel, R., Celikel, T., and Martin-Villalba, A. (2009). The death receptor CD95 activates adult neural stem cells for working memory formation and brain repair. Cell Stem Cell 5, 178-190.
Kleber, S., Sancho-Martinez, I., Wiestler, B., Beisel, A., Gieffers, C., Hill, O., Thiemann, M., Mueller, W., Sykora, J., Kuhn, A., Schreglmann, N., Letellier, E., Zuliani, C., Klussmann, S., Teodorczyk, M., Grone, H.J., Ganten, T.M., Sultmann, H., Tuttenberg, J, von Deimling, A., Regnier-Vigouroux, A., Herold-Mende, C., and Martin-Villalba, A (2008) Yes and PI3K bind CD95 to signal invasion of glioblastoma. Cancer Cell, 13, 235-248. This article was picked and evaluated by “Faculty of 1000” members with a F1000 Factor of 3.2.http://f1000medicine.com/article/id/1119774/evaluation
Sancho-Martinez, I. and Martin-Villalba,A. (2009). Tyrosine phosphorylation and CD95: a FAScinating switch. Cell Cycle 8, 838-842.