PROJECT SUMMARY/ABSTRACT The Experimental Irradiators Shared Resource (EISR) maintains and operates sources of ionizing radiation for use in experimental and preclinical studies by Sidney Kimmel Comprehensive Cancer Center (SKCCC) Members. The resource supports discovery research in DNA damage, cancer biology, radiation biology, immunology and preclinical and translational research using cell models; xenograft, orthotopic and syngeneic tumor models; and advanced genetically modified mouse models of cancer. Services performed by the resource staff include training in the operation of the instruments, advising users on the design of experiments, treatment planning (dosimetry) and educating users on new technologies. Resource staff oversee all instrument operations, assist users and operate the instruments when necessary, and conduct appropriate instrument maintenance and repair. The resource is also available to nonmembers on an increased-fee basis when not in use by Members. EISR resources include a parallel-opposed dual X-ray source system, an X-ray source system, an image-guided orthovoltage small-animal radiation research platform (SARRP) and two Cs-137 irradiators. The SARRP, located in the SKCCC Cancer Research Building II, is equipped with onboard cone beam CT to guide precise focal irradiation of small animals, mimicking human radiation treatments. SARRP represents highly sophisticated technology initially developed at Johns Hopkins and is under continuous development to incorporate molecular optical (bioluminescence and fluorescence) tomography for response assessment. These advances offer users unparalleled opportunities for precision radiation treatments and testing in model systems relevant for clinical translation. SKCCC Managed Shared Resource Reporting Period: January 1, 2020 to December 31, 2020