Hormone Dependent Cancer

Histone modifications such as acetylation, methylation, and phosphorylation are dynamically deposited and removed by histone code 'writer' and 'eraser' enzymes, and specifically recognized by 'reader' proteins. Together, writers, readers, and erasers contribute to the control of cell functions by regulating chromatin structure and gene transcription. Importantly, these epigenetic regulators have been implicated in various types of disease including cancer, which makes them an interesting class of potential therapeutic targets.

One research focus of our laboratory is the investigation of in vivo functions of methyl lysine reader proteins. Projects combine the generation and characterization of transgenic and knockout mouse models with genome-wide epigenetic, proteomic, and molecular biology analyses to identify epigenetic mechanisms relevant to normal and aberrant cell function.

In addition, we aim to identify small molecule inhibitors of methyl lysine reader domains. Inhibitor-reader complexes are characterized structurally and functionally in order to evaluate the potential of small molecules as molecular probes or therapeutics.

In summary, our laboratory applies multiple techniques ranging from protein crystallography and molecular biology to genetic manipulation of mice in order to gain mechanistic insight into the functions of epigenetic regulators under physiological and patho-physiological conditions.

Literature

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. 23;8(11):e3173. doi: 10.1038/cddis.2017.468.

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