Prof. Dr. Hans Gerd Nothwang
Department of Neuroscience
School of Medicine and Health Sciences
Carl von Ossietzky University Oldenburg
Prof. Kathrin Thedieck
Lab for metabolic signaling
European Medical School Oldenburg-Groningen
Lab of Pediatrics
University Medical Center Groningen (UMCG)
Patricia Razquin Navas
PhD completed in May 2020
PhD completed in December 2020
Summary: The PI3K (phosphoinositide 3-kinase) - mTOR (mammalian target of rapamycin) network senses nutrients, growth factors and cellular energy and is a master regulator of metabolism in all eukaryotes from yeast to mammals. The PI3K-mTOR network is recognized as a central determinant of development and ageing, and harbors numerous drug targets for the treatment of tumors and neurodevelopmental as well as neurodegenerative diseases. Even though PI3K-mTOR signaling is altered in a large proportion of cancers, not all patients respond to the treatments. Due to the network’s complex dynamics and wiring, involving multiply intertwined feedback loops, it is currently impossible to predict therapy response for specific patients and tumor types.
We tackle this complexity by systems approaches to simulate and analyze the PI3K-mTOR network dynamics and to unravel their complex dysregulation in cancer. Using data-driven computational models, we aim at individualized, targeted drug interventions. This also entails molecule quantification in clinical samples to enable higher data accuracy and sensitivity for model parametrization.
- Prentzell, M. T., Rehbein, U., Cadena Sandoval, M., De Meulemeester, A. S., Baumeister, R., Brohée, L., Berdel, B., Bockwoldt, M., Carroll, B., Chowdhury, S. R., von Deimling, A., Demetriades, C., Figlia, G., Genomics England Research Consortium, de Araujo, M., Heberle, A. M., Heiland, I., Holzwarth, B., Huber, L. A., Jaworski, J., … Thedieck, K. (2021). G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling. Cell, 184(3), 655–674.e27
- Heberle, A. M., Rehbein, U., Rodríguez Peiris, M., & Thedieck, K. (2021). Finding new edges: systems approaches to MTOR signaling. Biochemical Society transactions, 49(1), 41–54.
- Heberle, A. M., Razquin Navas, P., Langelaar-Makkinje, M., Kasack, K., Sadik, A., Faessler, E., Hahn, U., Marx-Stoelting, P., Opitz, C. A., Sers, C., Heiland, I., Schäuble, S., & Thedieck, K. (2019). The PI3K and MAPK/p38 pathways control stress granule assembly in a hierarchical manner. Life science alliance, 2(2), e201800257.