Tumors of all tissues emerge due to the sequential acquisition of genetic alterations, leading to oncogene activation and loss of tumor suppressor functions. Our research focus is on the ErbB/HER family of receptor tyrosine kinases and the DLC family of tumor suppressors and their contribution to cancer cell survival and proliferation, invasive migration, and drug resistance when deregulated. We further have a special interest in understanding how cellular membranes assemble and regulate protein signaling complexes. To address these scientific questions, the lab utilizes advanced biochemical and molecular biology techniques, 2D/3D cell and organoid culture models in combination with state-of-the-art imaging and genome editing approaches.
Tumor Suppressors in Invasive Cell Migration
Rho GTPases play a pivotal role in the regulation of cytoskeletal dynamics associated with diverse cellular processes such as membrane trafficking, cell migration and invasion. Rho signaling is regulated positively by GEF proteins on the one hand and negatively by GAP proteins on the other. The GAP protein Deleted in Liver Cancer 1 (DLC1) has emerged as an important tumor suppressor, whose downregulation in various types of cancer may be as common as that of p53. Our work has shown that DLC1 loss facilitates the aberrant migration of breast cancer cells, whereas DLC3 expression is crucial for the establishment and maintenance of cell polarity and cell-cell adhesions. We are especially interested in unraveling how specific GEF-GAP networks regulate spatiotemporal Rho signaling and how dysregulation contributes to the metastatic behavior of cancer cells.
Oncogenic Signaling Networks in Cell Transformation
The ErbB family of receptor tyrosine kinases plays a well-established role in cancer development and progression. ErbB2/HER2, for example, is amplified and/or overexpressed in approximately 25% of breast cancer patients, correlating with poor clinical prognosis, whereas EGFR/ErbB1 expression is elevated in 70% of triple-negative breast cancers. Despite being prime targets for pharmacological intervention in the clinic, cancer cells are often non-responsive or become resistant to treatment. We aim to increase the understanding of how ErbB receptor signaling is regulated by cell-autonomous mechanisms and interactions with the tumor microenvironment. In collaboration with the lab of Prof. Roland Kontermann we are developing bispecific antibodies that target defined combinations of receptor tyrosine kinases as a strategy for the improved treatment of solid cancers.
Collaborative Research Projects: PKD signaling networks in cancer (with PD Dr. Angelika Hausser)
The PKD family of serine/threonine kinases plays an established function at Golgi membranes where it controls vesicle fission. However, the PKD substrates that mediate this function have long been elusive. In a team effort with the Hausser lab, we identified the ceramide transfer protein CERT as a PKD substrate within a signaling loop required for Golgi secretory function. Our work has further uncovered novel roles for PKD in the regulation of actin dynamics and cell motility. Importantly, we found PKD3 to be upregulated in triple-negative breast cancer where it drives cell proliferation. By mapping the PKD3 interactome and kinome our goal is to identify druggable signaling nodes for this cancer type.
We further work in close collaboration with Prof. Matthias Schwab (Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart), Prof. Christine Sers (Charité, Berlin), Prof. Tilman Brummer and Dr. Dr. Melanie Boerries (University of Freiburg), Prof. Hauke Busch (University of Luebeck), and Prof. Boris Macek (Proteome Center Tübingen).
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Monilola Olayioye (PI)
Cristiana Lungu (Postdoctoral Scientist)
Raluca Tamas (Postdoctoral Scientist)
Bettina Noll (Postdoctoral Scientist)
Yannick Frey (PhD student)
Lisa Brenner (PhD student)
Merih Özverin (PhD student)
Florian Meyer (PhD student)
Lennart Kühl (joint PhD student with the Kontermann lab)
Alex Rau (joint PhD student with the Kontermann lab)
Simone Schmid (Technician)
How to join our Group
Undergraduate students interested in conducting a BSc/MSc research project should get in touch at an early stage with their CV as space is limited. PhD and postdoctoral positions are advertised on the institute website. We are happy to support highly qualified and competitive candidates that wish to apply for fellowship funding programs to join our research team