PROJECT SUMMARY/ABSTRACT With an emphasis on the integration of basic, translational, and clinical approaches, the 65th annual Aspen Lung Conference will focus on a central question: how can knowledge of the molecular, genetic, and environmental mechanisms that underlie the development and phenotypic diversity of asthma be translated into more effective therapies? To address this central question, the program is organized into a series of thematic sessions, with State of the Art speakers framing each topic. The thematic sessions will focus on (i) the developmental origins of asthma, (ii) the role of cell biology in defining asthma endotypes, (iii) microbiome and immune mechanisms underlying asthma pathogenesis, (iv) integrated cell and molecular mechanisms contributing to the clinical complexity of asthma, and (v) the future of asthma therapeutics. By addressing these topics, we seek to accomplish the following: 1) provide an international forum for leading basic, translational, and clinical researchers to exchange ideas regarding the development and cell type specific roles of the airway and immune system in the phenotypic and molecular manifestations of asthma; 2) stimulate interactions between scientific fields to identify emerging and shared interests that may lead to more efficient and productive research; 3) enhance the likelihood of success in translation of preclinical scientific advances into direct patient benefit by developing novel strategies to better understand disease pathogenesis and implement scientific advances in the treatment of asthma; and 4) challenge and stimulate the scientific interests of trainees and attract a new generation of early career investigators into the broad field of asthma, as well as underlying subdisciplines including airway and lung immune cell biology, genetics, and environmental impacts. We have identified 12 outstanding thought leaders to present State of the Art lectures (35 min) on these topics. Each presentation will be followed by 25 minutes of discussion - a hallmark of the Conference. The program continues the Aspen Lung Conference’s dedication to diversity and inclusivity: n=8/13 (62%) of State of the Art speakers/Summarizer are women, and at least 6 of our speakers are from underrepresented racial/ethnic groups. Participation of trainees and early career faculty is facilitated by two 15-minute oral abstracts, selected from submitted abstracts, following each State of the Art speaker (24 total). There will be two evening poster sessions for further presentation opportunities by early career faculty and trainees. The final presentation is provided by a Conference Summarizer, who reviews the impact and common themes of the Conference. The Conference Summary will be published for widespread dissemination, to serve as a “think tank” that not only summarizes the current state of the field, but also identifies key future directions for basic, translational, and clinical asthma research. Finally, and n...