Departmental Seminar: Dr. Hartmut Land

Event Date: 11.25.2013 Day: Monday Time: 12:00 pm Location: 700 Fairchild Event Type: Departmental

Abstract

Carcinogenesis is a process driven by multiple co-operating oncogenic mutations in which features of the cancer cell phenotype, such as proliferative advantage, only emerge as a result of the interplay between these mutations. This is consistent with the notion that many divergent cancers share a limited number of disease mechanisms with common underlying signaling networks, despite the many genes implicated in the disease. The Land laboratory has pioneered investigation of the nature and underlying principles of cancer gene cooperation originating with the discovery that multiple oncogenic mutations are required for malignant cell transformation. Using a wide variety of experimental approaches, the laboratory has demonstrated that the cooperation of cancer-promoting genetic lesions is strongly reflected by synergistic modulation in signaling and the gene networks of malignant cells. The lab has identified molecular events downstream of cooperating oncogenic mutations that are critical to cell transformation. Using genomic approaches, approximately 100 genes that alter their expression synergistically in response to the combined effect of two oncogenic mutations were identified. Importantly, the regulation of these ‘cooperation response genes' (CRG) is critical for the cancer phenotype at surprisingly high frequency, indicating that oncogenic mutations cooperate through synergistic regulation of downstream gene networks. CRGs control diverse cellular processes, including cell signaling, motility, survival and cell metabolism etc., thus indicating how cooperating oncogenic mutations ultimately affect multiple parallel cancer cell traits.