PROJECT SUMMARY/ABSTRACT The Imaging and Engineering Core includes the following components: 1) Imaging platforms that harness UCI's proficiency in multiphoton microscopy, fluorescence dynamics, and diffuse optical imaging. These platforms enable data acquisition across various scales, from laboratory experiments to animal models and clinical environments. 2) Tissue engineering and labeling approaches that, in conjunction with tissue clearing and advanced imaging techniques, facilitate the exploration of genotype-phenotype relationships in the epidermis. In the last four years, Core investigators have employed state-of-the-art technologies, including Multiphoton Microscopy, Fluorescence Lifetime Imaging Microscopy, Coherent Raman Scattering, Spatial Frequency Domain Imaging (SFDI), and Laser Speckle Imaging (LSI), to obtain groundbreaking findings in skin homeostasis and disease. This research has yielded 28 peer-reviewed papers utilizing core services and 13 papers contributing to the advancement of skin imaging technologies. Over this same timeframe, UCI Skin investigators have expressed a need for advanced spatial phenotyping methods capable of visualizing molecular contrast at cellular/subcellular resolution in vitro, in vivo, and in human skin at the bedside. In response to this need, we develop advanced imaging methods capable of visualizing molecular contrast at subcellular resolution. To explore how genotype impacts the spatial distribution of molecular contrast in tissue, we engineer tissue models to examine genotype-phenotype relationships relevant to skin disease. The Imaging and Engineering Core has a crucial role in offering resources for training, dissemination, and collaboration that foster and bolster interdisciplinary efforts. Our aim is to unite technology developers, modeling experts, biologists, and clinicians from UCI and the broader skin research community, forming teams that can exchange knowledge and utilize new tools to address persistent challenges. This will be achieved through hands-on and didactic training, as well as dissemination activities designed to equip skin biology researchers with advanced imaging tools for their research.