Despite almost two decades of tobacco treatment research, treatment options for smoking cessation remain limited. Over the past 4 years, our TTURC has begun to address this gap in knowledge and practice. In our pharmacogenetic trials of nicotine dependence treatment, we have provided the first evidence for effects of specific genetic variants on smoking cessation and response to pharmacotherapy, generated new data on bio-behavioral mechanisms of response to treatment, developed new tools and applied new methods to analyze smoking cessation clinical trial data, and identified pre-treatment measures that can be used in clinical practice to tailor choice of treatment for individual smokers. In addition, we have completed a national survey of over 1000 physicians in the AMA, and have begun to identify emerging health policy and ethical issues in the translation of our research to clinical practice. A milestone event in the evolution of our TTURC was the move to the University of Pennsylvania in 2001. This move provided new opportunities for transdisciplinary collaboration, an enhanced institutional commitment, and access to state-of-the art facilities for biomedical informatics, genotyping, and animal models research. The mission of this competing renewal application for the Penn TTURC is to translate new discoveries in basic neuroscience, pharmacology, genetics, and behavioral science to improve treatment for nicotine dependence. The specific aims are: (1) To conduct 4 inter-related projects which test new treatments for nicotine dependence and test novel approaches to optimize the use of existing treatments; (2) To support and integrate TTURC research through a state-of-the-art Biomedical Informatics Core and Genetics Core; (3) To facilitate the diffusion and clinical integration of TTURC research through a novel Research to Practice Core which addresses key policy and ethical issues; (4) To train tobacco control scientists through a Training Core; and (5) To coordinate and facilitate transdisciplinary collaboration through an Administrative Core. Spanning from basic animal research to clinical trials ("bench to trench"), the ultimate objective of the TTURC is to develop new treatment models that can be readily translated to the clinical setting in order to maximize the efficacy of pharmacotherapy for individual smokers.