DESCRIPTION (provided by applicant): As a Nuclear Medicine physician and translational Neuroscientist, my long-term career goal is to establish an independent career in patient-oriented research (POR), focused on understanding the changes in brain function which occur in nicotine dependence, and how they can be shaped to achieve cessation and improve public health. My prior training has enabled me to help design and conduct translational positron emission tomography brain imaging studies in humans. My graduate level training in neuroscience focused on pre- clinical animal models and wet-laboratory techniques used to study the dynamic reorganization of the mammalian central nervous system. This training in basic science research will serve as the foundation for the design of the translational studies I plan on pursuing as a clinician-scientist. My medical training including medical school, internship and Nuclear Medicine residency provided me with fundamental knowledge of health and disease, and directed me to a clinical specialty in Nuclear Medicine, in which I am board certified. As I move to independence in my research career, it is critical that I address gaps in my knowledge and training to achieve my long-term goals. I was appointed to Assistant Professor of Radiology at the University of Pennsylvania's (UPenn) Perelman School of Medicine on January 1, 2012. Despite a significant burden of clinical and teaching responsibilities, I have been able to pursue my interests and passions in translational neuroreceptor research at UPenn. However, to make a significant contribution to the neurobiology of substance abuse, I require additional training and protected research time. The goal of this K23 award is to enable me to focus at least 75% of my time to conduct the research and complete the training described in this grant proposal that will help me develop as an independent investigator. My proposed training objectives will empower me to progress in a logical trajectory towards this goal. These include (1) acquiring new knowledge in PET quantification techniques, and the design of neuroreceptor imaging studies capable of probing the relationship between addiction pharmacogenetics and the behavioral pharmacology of craving of nicotine; (2) conducting a novel study examining the dynamic interaction between a psychoactive compound (i.e., nicotine) and receptor occupancy (α4β2 receptors and dopamine D3 receptors) in order to further understand the neurochemical mechanisms of drug craving (3) developing the tools to communicate my research findings, collaborate in a dynamic multidisciplinary environment, and secure extramural funding of my research program. I will accomplish these training objectives through the proposed research, relevant coursework, guidance from my mentor and mentorship committee, attendance at seminars and workshops, and applied hands-on research training as the research evolves. This multi-faceted approach will empower me wi...