We are requesting funds to purchase a ArcturusXT? Laser Capture Microdissection (LCM) System from Life Technologies. We chose this instrument because it specifically suits the needs of our users, who need the ability to isolate and enrich specific populations of cells for molecular analysis. The ArcturusXT? LCM instrument is a dual laser system that combines ultraviolet (UV) laser cutting with gentle capture by infrared (IR) laser. The ArcturusXT? LCM is based on the Nikon Eclipse Ti-E research microscope and is completely modular and fully upgradeable. This system allows rapid and accurate microdissection of both small and large groups of cells and can be used with phase contrast for live-cell applications, with stained tissue samples and transmitted light, or with epi-fluorescence for fluorescence tagged targets. This system will be used to support the work of several VA investigators interested in cancer biology and diabetes. Several of the proposed users are focused on melanoma, the deadliest skin cancer whose occurrence is steadily increasing in the US military, especially in Veterans who served outdoors and were exposed to UV radiation for prolonged periods. Melanoma can be cured if diagnosed early, but advanced melanoma that has spread beyond skin is often deadly because there are not many effective treatments. Dr. B. Jack Longley who studies early events in the development of melanoma from melanocytic nevi will use LCM to isolate cells of defined phenotypes and perform unbiased analysis of nevomelanocyte heterogeneity, increasing understanding of the mechanisms involved melanomagenesis. Dr. Nihal Ahmad, a VA Research Career Scientist focused on melanoma development and progression, will use LCM to isolate and analyze single cells from preserved melanoma tissue samples. Dr. Vijay Setaluri focuses on the molecular mechanisms involved in homeostasis of melanocytes and their malignant transformation. Dr. Setaluri will use LCM to isolate and analyze subpopulations of melanoma tumor cells in an attempt to discover novel biomarkers. Dr. Gary S. Wood is an expert in expert in cutaneous lymphomas and plans to use LCM to better understand epigenetic regulation of tumor suppressor genes important in cutaneous T-cell lymphoma?a cancer type that has been linked to linked to Agent Orange exposure by the VA. Dr. Stefan Schieke is also interested in cutaneous T cell lymphoma and will use LCM of archived tissue sections from patients paired with transcriptome analysis to obtain a molecular signature of the relapse-inducing cells in cutaneous lymphoma. Dr. Dawn Davis, a diabetes researcher, studies the role of specific genes in the regulation of growth and survival of pancreatic beta cells that synthesize, store, and release insulin. She will use LCM to isolate beta cells from pancreatic islets for further molecular analysis. Finally, Dr. Stefanie McGregor will use LCM to isolate and study precursor lesions of vulvar cancer with the goal of more accurately and reproducibly diagnosing vulvar cancer. The long-term objective of the investigators involved in this application is to obtain a better understanding of molecular underpinnings of disease (malignant transformation and diabetes) with the ultimate goal of improving healthcare for Veterans. The requested ArcturusXT? Laser Capture Microdissection System is critical for progress in these important areas.