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The mission of the Drug Discovery Platform is to technically support the drug discovery research activities by developing and providing highly innovative techniques such as antibody engineering, cancer cell engineering, and mouse genetic engineering.
Antibody Engineering
Antibodies are key players in the immune system and antibodies are used in many applications, such as immunohistochemistry, FACS and ELISA. Recently, antibodies are also used as antibody therapeutics.
Our team has developed many monoclonal antibodies against secreted proteins or transmembrane proteins. Especially, we are focusing on the development of antibodies against multispanning transmembrane proteins, such as GPCRs or channels. We are now trying to establish a platform for antibody development against GPCRs through installing or developing new technologies. Monoclonal antibodies are made by a conventional method; injecting the antigen into mouse or rat. Because the antibodies produced this way are potentially immunogenic when administered to human patients, humanization process in which these antibodies are modified to increase their similarity to human antibodies is needed. Development of humanized antibodies produced in-house for new antibody therapeutics is ongoing.
Cancer Cell Engineering
 The mission of this team is engineering cancer cell models which are useful to discover novel targets or concepts for innovative cancer therapy.
Considering that more than 85% of human cancer has epithelial origin, it is quite important to use human epithelial cells for the study of oncogenic transformation. So far, though, this type of experiment has been conducted extensively with rodent cells but only very limitedly with human cells, because it is empirically known that human cells are much more resistant to oncogenic transformation. However, an increasing body of evidence indicates the existence of fundamental differences in cancer biology between human and rodent cells. For instance, there are considerable differences in the regulation of telomerase, an enzyme involved in cellular senescence, and several tumor suppressors including p53, p16INK4, p19ARF. Therefore, it is now considered impossible to fully understand the mechanism of malignant transformation of human cells using rodent cells.
Starting from normal human epithelial cells, we have already succeeded in engineering several kinds of tumor cells with different levels of differentiation and malignancy by improving the culture conditions and gene transfer methods. Some of them have shown to form tumors with histopathological features similar to those of clinically observed non-small cell lung cancer (NSCLC) when xenografted into nude mice. Besides continuing the characterization of these NSCLC models, we are trying to establish new more clinically relevant cancer cell models to contribute to discovery of novel therapeutic targets and novel therapeutic concepts.
Transgenic Engineering
Our body is composed of multiple tissues that contain many types of cells and these tissues cooperatively function to maintain the life. Disruption or dysfunction of some tissues or cells causes disease. To elucidate the function of specific tissues, cell types or genes, particularly in disease progression or tissue homeostasis, in vivo analyses of transgenic knockout or knockin mice is a powerful method. In some cases, transgenic mice exhibit a phenotype similar that of a specific human disease and can be used as a model system for this disease. Our group's aim is to efficiently generate transgenic mice using new technologies, in order to analyze gene function and establish new disease models.
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