Werr Lab

Telomerase is activated in the majority of human cancers and considered to essentially contribute to immortalization of malignant cells. Reactivation of telomerase enables cells to overcome replicative senescence by maintaining telomeres above a critical threshold, and thus provide cancer cells with the capacity to divide indefinitely. The significance of telomerase activation in tumorigenesis has been substantiated by several animal models, in which constitutive telomerase expression led to an increased incidence of spontaneously developing tumors. Conversely, the phenomenon of spontaneous tumor regression - frequently observed in neuroblastoma and occasionally in other cancers such as melanoma, renal cell carcinoma, and CLL - remains poorly understood at the mechanistic level.

Our research focus:

Activation of telomere maintenance is a key event in malignant transformation and most frequently conferred by induction of the reverse transcriptase telomerase encoded by TERT. In previous studies, we demonstrated that spontaneous regression and maturation occur frequently in Tert-deficient tumors, however, the mechanisms underlying these phenomena have remained uncertain. In our current research focus, we will investigate the molecular mechanisms underlying spontaneous regression in SCLC, with a special focus on cell death mechanisms.

Our goals:

Unraveling the exact mechanisms of spontaneous regression and the predominant cell death mechanism is essential to develop therapies targeting telomere maintenance and possible therapeutic combinations to not only cause telomere dysfunction but to also enhance the resulting cell death mechanism to induce tumor regression that translates to a clinical response of the patient.

Our approach:

Using genetically engineered mouse models and in-depth comparison of murine and human tumors, we analyze processes and cell death mechanisms involved in spontaneous regression. Tumors will be analyzed using bulk and single nuclei RNA sequencing to generate testable hypotheses, which will subsequently be evaluated through complementary analyses.