Johannes Hanewinkel

Validation of novel substrates of the tumor suppressor LKB1

As a cellular master kinase, Liver Kinase B1 (LKB1) regulates major cellular processes including polarity, migration, apoptosis, metabolism and inflammation through activation of several downstream proteins. On a molecular basis, LKB1 also plays a role in tumor suppression controlling apoptosis and cell cycle arrest.

To obtain further insights into LKB1-dependent regulation and the consequences of impaired LKB1 function, my project aims to investigate the interaction between LKB1 and three novel target proteins: End-binding 1, Histone 2B and Lethal(2) Giant Larvae. Therefore, transgenic Drosophila flies will be used as in vivo model organisms, while MDCK cells and DLD1 colorectal cancer cells are used as in vitro models. The results of this project will provide new insights into the regulatory mechanisms of LKB1 in these model systems, especially in the context of cell polarity, migration and cell cycle/cell proliferation. In addition, colorectal cancer specimen will be investigated regarding the consequences of LKB1 defects in human gastrointestinal malignancies.