In spite of the long history of achievements in the study of the critical effects of radiation on normal tissues in vitro and in vivo, there is a dearth of agents immediately available for prophylaxis, mitigation and treatment of radiation injury, a lack of high throughput methods to assess efficacy, an absence of biodosimetry devices to identify individuals who need treatment, and a shortfall in the number of personnel appropriately trained to advance these fields. The goal of the UCLA-CMCR is to develop a drug discovery, evaluation, and development infrastructure that can identify novel agents and test them, alongside agents of known potential, for their ability to ameliorate the effects of radiation on normal tissue damage. Their potential to enhance radio-carcinogenesis will also be assessed, since this is an important aspect of radiation exposure. Multiple high and low throughput screening assays will be performed that will allow compounds to be selected for further characterization by LTS assays. One concept that will be explored is that molecular """"""""signatures"""""""" can be used to classify modulators of radiation responses and can be exploited for rational development of effective agents. After further selection, compounds will be tested in vivo for efficacy and toxicity and, if successful, will be entered into as product development plan. The ordered evaluation of agents within one center is the optimum way of speeding up product development for validation, licensing, and inclusion of products in the Strategic National Stockpile. The UCLA CMCR will have a lean structure but a broad focus. It integrates harnesses multiple strengths at UCLA to the CMCR Program and builds a rich environment for research, training, and product development in radiation sciences. Other members of the CMCR network, groups and individuals in academic and commercial entities will evaluate agents in our model systems and we will utilize other CMCRs to test our compounds for efficacy in their systems. In this way it will link to industry and to the CMCR Program as a whole.
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