X-ray irradiation is widely used in both imaging applications and radiotherapy. Small-animal imaging plays an important role in phenotyping, drug discovery, and in providing information on mechanisms of disease. Imaging-guided irradiation of small animal is crucial in implementing novel radiation therapy as well as in understanding molecular mechanisms of early and late effects of ionizing radiation. Recently an advanced small animal radiation research platform (SARRP) was made commercially available with the support of the Bioengineering Research Partnership mechanism. This system, which uses a dual focused X-ray tube for both imaging and radiation delivery, is an important advancement in addressing the needs of clinical, translational, and basic radiation research in that it provides real time imaging for target localization. At the cancer center of Columbia University, there are many NIH funded research projects that require partial-body or organ-specific X-ray irradiation of small animals. Examples of the many applications are: development and assessment of an organ-specific chemo- radiotherapy technique based on the mouse model;irradiate one kidney and examine the bystander signaling pathways involved in the other kidney to understand the cellular and molecular mechanisms of the bystander effect;partial-body irradiation animal studies to address issues of partial-body exposure from a Radiological Dispersal Device (RDD) or an Improvised Nuclear Device (IND) event. As such, the ability to target specific tissues/organs with high precision, without affecting adjacent tissues, is highly desirable but currently not available at Columbia. The shared instrument we request fills this need is the SARRP 200, which supports (1) isocentric and noncoplanar conformal irradiation;(2) onboard CT guidance to facilitate accurate repositioning for fractionated irradiation schemes and co-registration with other small animal imaging modalities;and (3) 3D conformal treatment planning to provide quantitative dosimetry. This instrument will be maintained and operated as part of the established Radiation Research Core Facility of the Columbia Herbert Irving Comprehensive Cancer Center. Using SARRP, we will develop and test imaging and treatment techniques applicable to radiation oncology, and support physicians and radiation biologists to address issues encountered in radiotherapy. To meet the unique needs of different researchers, an internal advisory committee has been formed not only to assist the PI of this proposal to administer the grant, and oversee the maintenance and use of the instrument, but also to offer advice on research design to investigators as needed.