不良研究所

Dr. Brodt and her group are studying the molecular aspects of cancer metastasis. In particular, the roles of cell adhesion receptors, cytokines and growth factors in the regulation of angiogenesis, cancer cell invasion and metastasis. One project looks at the role of the type 1 Insulin-like growth factor receptor (IGF-1R) in metastasis and the signal transduction pathways involved in transcriptional regulation by IGF-IR, using a combination of approaches that include gene transfer, use of dominant negative mutants and promoter assays. The contribution of different receptor domains to the transcriptional regulation of different genes is also being investigated, as is the role of post- internalization receptor processing in trafficking and signaling.

Another area of interest to the group is gene therapy of cancer metastases. Multiple strategies are being developed for gene therapy of metastases based on the targeting and disruption of IGF-IR synthesis and/or signaling. These strategies are being tested in several cancer types including lung carcinomas, colorectal carcinomas, breast carcinomas and brain tumours.

Finally, Dr. Brodt and her team are also looking at the role of the host inflammatory response in liver metastasis. The molecular cascade that is initiated following tumour cell entry into the hepatic circulation is being investigated by a combination of in vivo and in vitro techniques. In particular, the role of cytokines such as TNF飦� and IL-1 and of vascular endothelial adhesion receptors such as E-selectin, VCAM-1, PECAM-1 and ICAM-1 are being analysed using a combination of immunohistochemistry, fluorescence based techniques, molecular analyses and animal studies.