Project Summary Career Development Plan: This supplement will support Alex Smith, M.S. for 1 year while he is applying to graduate school. Alex’s career goals are to attend graduate school and then long term to become an academic researcher and educator in cancer immunology. This research year will provide Alex with time to master new technical skills, expand cognitive experimental design skills, practice interpreting results and planning appropriate next steps, and gain additional education in research, including ethics and communication. Alex will complete a detailed plan of research and career development activities outlined in the proposal, which will support his application for PhD programs. He will regularly interact with the PI, Dr. Tennis, and a career development advisory committee, who will monitor the successful completion of the proposal and will provide feedback on the experimental research plan and training. Alex will also complete courses at the University of Colorado Anschutz Medical Campus to expand the knowledge base to guide him through his training, including training in the responsible conduct of research. We expect that Alex will attend and present at divisional conferences and a national meeting, and publish a first author paper reporting his findings. Research Plan: Lung Cancer continues to be the leading cause of cancer death in the United States. Most of lung cancer research is focused on therapy rather than preventing the progression of premalignant lesions. Frizzled 9 is a key receptor for chemoprevention with the prostacyclin analogue iloprost. The research goal of this supplement will be to expand investigation of role of Frizzled9 (Fzd9) in lung epithelial cells by exploring interactions with the microenvironment. The goal of Aim 1 is to establish if Fzd9 and cytokine production are linked in lung epithelial cells. To do this, we will treat epithelial cells with various cytokines to measure Fzd9 expression and test the effects of manipulation of Fzd9 expression on cytokine production. The goal of Aim 2 is to understand the role of Fzd9 in primary macrophage cytokine expression and function. We will use macrophages from bronchoalveolar lavages of wildtype and Fzd9 -/- mice. This supplement will increase our understanding of the activity of Fzd9 in epithelial cells and macrophages and build a foundation for future studies investigating Fzd9 and the microenvironment.