Hormone Dependent Cancer

Propagation and differentiation of stem cell populations are tightly regulated to provide sufficient cell numbers for tissue formation while maintaining the stem cell pool. We are interested in molecular mechanisms that link cell signaling, gene transcription, and chromatin modification with the threshold level for differentiation onset and with the determination of cell fate.

The generation of conditional gene deletions and mutations using the mouse as model system allows us to unveil the impact of signaling molecules, epigenetic enzymes, and transcription factors on the retention of homeostasis. In addition, we establish primary stem cell cultures from various organs.

Targeted genome editing by introduction of heterozygous or homozygous mutations and reporters enables us to study the molecular mechanisms directing stemness and differentiation in these cell lines. We use state-of-the-art technology to detect interacting proteins and differential gene expression and epigenetic modifications on a genome-wide basis. The comprehension of stem cell maintenance and differentiation is essential for the generation of induced pluripotent stem cells, tissue engineering, and treatment of cancer stem cells.

Literature

Koch S.C., Del Barrio M.G., Dalet A., Gatto G., Günther T., Zhang J., Seidler B., Saur D., Schüle R., Goulding M. (2017). RORβ Spinal Interneurons Gate Sensory Transmission during Locomotion to Secure a Fluid Walking Gait. Neuron 96(6):1419-1431.e5

Greschik H., Duteil D., Messaddeq N., Willmann D., Arrigoni L., Sum M., Jung M., Metzger D., Manke T., Günther T., Schüle R. (2017). The histone code reader Spin1 controls skeletal muscle development. Cell Death Dis. 8(11):e3173.

Castex J., Willmann D., Kanouni T., Arrigoni L., Li Y., Friedrich M., Schleicher M., Wöhrle S., Pearson M., Kraut N., Méret M., Manke T., Metzger E., Schüle R., Günther T. (2017 )  Inactivation of Lsd1 triggers senescence in trophoblast stem cells by induction of Sirt4. Cell Death Dis. 8(2):e2631. doi: 10.1038/cddis.2017.48.

Greschik H., Schüle R., Günther T. (2017) Selective targeting of epigenetic reader domains. Expert Opin Drug Discov. Mar 14:1-15.

Fedorov O, Castex J, Tallant C, Owen DR, Martin S, Aldeghi M, Monteiro O, Filippakopoulos P, Picaud S, Trzupek JD, Gerstenberger BS, Bountra C, Willmann D, Wells C, Philpott M, Rogers C, Biggin PC, Brennan PE, Bunnage ME, Schüle R, Günther T, Knapp S, Müller S (2015) Selective targeting of the BRG/PB1 bromodomains impairs embryonic and trophoblast stem cell maintenance..Sci Adv. 1(10):e1500723

Zhu, D., Hölz, S., Metzger, E., Pavlovic, M., Jandausch, A., Jilg, C., Galgoczy, P., Herz, C., Moser, M., Metzger, D., Günther, T., Arnold, S.J. and Schüle, R. (2014) Lsd1 regulates differentiation onset and migration of trophoblast stem cells Nat. Commun. 5, 3174-3184.