Marcus Thelen

Marcus Thelen studied biochemistry at the University of Tübingen (DE) and received his PhD from the University of Bern in 1985. As postdoc at the Theodor-Kocher-Institute in Bern, his interests focused on inflammation and chemokines. In 1989, he went to the Rockefeller University in New York, joining the group of Alan Aderem in the Laboratory of Cellular Physiology and Immunology of the Cohn/Steinman department. Biochemical aspects of cytokine- and endotoxin-mediated phagocyte priming and cytoskeleton-mediated signal transduction were the topics of his studies. In 1992, he received a career development award (START) from the Swiss National Science Foundation and returned to the Theodor-Kocher-Institute at the University of Bern. He created his own research group working on molecular mechanisms of signal transduction in leukocytes, focusing on PI 3-kinase-dependent pathways and chemokine-mediated receptor activation. He obtained the venia docendi in 1994 and received an honorary professorship in 2001 from the University of Bern. In 2000, he moved to Bellinzona and assisted in the opening of the IRB. Marcus Thelen heads since then the Laboratory of Signal Transduction.

Publications

Cell migration and positioning is principal feature in the organization of multicellular organisms. Cells migrate along predefined gradients to find their destinations. In adults, the most prominent cell movement is the continuous migration of immune cells during immune surveillance and host defense after infection. The chemokine system plays a critical role in these processes by orchestrating cell migration. In addition, the chemokine system can guide non-hematopoietic cells, e.g. during neovascularization. Many tumors express chemokine receptors und use chemokines for tissue invasion and metastasis.

Locally produced chemokines are presented on the surface of cells or extracellular matrix to form haptotactic gradients in close vicinity of the source (~100-150µm). Cells are guided by the gradients through the activation of G-protein coupled chemokine receptors. An important aspect for the maintenance and local confinement of gradients is the requirement of sinks in apposition to the source of attractant. Atypical chemokine receptors (ACKRs), recently defined as a separate group of receptors, which are structurally related to typical chemokine receptors, act mainly as sinks for chemokines. Through the scavenging activity, ACKRs can promote cell migration.

Since its discovery as receptor for CXCL12, ACKR3 (formerly CXCR7) emerged as critical regulator of the CXCL12/CXCR4 axis. ACKR3, which binds CXCL12 with higher affinity than CXCR4, modulates the activity of CXCR4 through the availability of CXCL12. The team is investigating on one side the role of ACKR3 in the formation and maintenance of local gradients in lymphoid tissue in the generation of efficient humoral immune responses; on the other side, the laboratory explores the function of ACKR3 in tumor development. Recent findings revealed that ACKR3 plays a critical role in lymphoma dissemination and might therefore be a potential target for therapeutic intervention.