Cancer Genetics and Cellular Stress Responses


Head of the Group

Prof. Dr. Clemens Schmitt

31.1: Max Delbrück House (Hochbau)

Room 1023

Tel. 9406-3370

Fax. 9406-3364

31.1: Max Delbrück House (Hochbau)

Room 1042

Tel. 9406-3758


Our program is driven by our interest in cellular stress responses (so called ‘failsafe mechanisms’) that may serve as anti-tumor barriers when challenged by transforming oncogenes, and, in turn, must be bypassed or inactivated before a full-blown malignancy can actually form. Importantly, ultimate stress responses such as apoptosis or cellular senescence – both terminal ‘cell-cycle exit’ programs – do not only counter tumorigenesis, but are utilized as chemotherapy-induced stress responses as well. Hence, principles of oncogenesis and mechanisms of treatment sensitivity seem to critically overlap and impinge on each other during tumor formation, cancer therapy and relapsed or progressive disease conditions. Our scientific scope spans from basic biology (e.g. chromatin remodeling in senescence) to conceptually novel therapies (especially strategies that utilize cancer ‘liabilities’ or build on synthetic lethal interactions). We are particularly interested in the connection of failsafe programs and cell metabolism as well as non-cell-autonomous implications of these programs, and, thus, primarily utilize mouse models harboring lymphomas (and other tumor entities) with defined genetic lesions as experimental platforms.

image B image C

Signaling oncogenes like Ras promote oncogene-induced senescence (OIS), while Myc-driven lymphomas, when expressing a strong anti-apoptotic activity such as Bcl2, will undergo therapy-induced senescence (TIS) in response to chemotherapy – which we model in cell culture and in transgenic lymphomas in mice (A). OIS and TIS are controlled by H3K9me3-governed chromatin remodeling, leading to firm silencing of S-phase-promoting genes (B). We are particularly interested in the function and fate of TIS lymphoma cells – in terms of their cellular condition (e.g. metabolic state, propensity to die) as well their interactive capabilities (i.e. to promote secondary senescence and to crosstalk to the host immune system (C).


Selected Publications