SUMMARY This proposal requests funds to acquire a hypoxic incubator and workstation in one, which provides precise control of temperature, humidity, oxygen and carbon dioxide levels. Oxygen levels can be controlled in 0.1% increments from 0.1% to 20%, thus encompassing the various levels found in tissues, including in tumors which often are extremely hypoxic with levels ranging between 0.3 and 2.0% oxygen. This application will directly support 6 NIH-funded investigators and 3 young investigators currently applying for NIH funding. Each of these investigators has specific projects that benefits from the unique aspects of the HypOxystation® H35 workstation. Cells that are under low oxygen tension accumulate and activate hypoxia-inducible transcription factor alpha- subunits HIF-1a and HIF-2a, leading to pleiotropic effects including modulating cellular metabolism, cell cycle and anti-inflammatory activities. Availability of this instrument will enable crucial investigations of the role of hypoxia in modulating the immunogenic effects of radiation, antigen presentation in cancer and diabetes, and mitochondrial dysfunction in autoimmunity. Unique features of the HypOxystation® H35, including a large workspace, sample input/output port, sleeve ports and precise environmental control and monitoring produce stable atmospheric conditions for culturing and manipulating samples, which is required for carrying out rigorous research into the role of oxygen tension within a biological system. The HypOxystation® H35 will provide capabilities to Weill Cornell Medicine and neighboring institutions and will be supervised by an advisory committee, overseen by the Radiation Oncology department, and will thus positively impact basic and translational NIH-funded research. The NIH-funded research programs supported by this instrumentation have relevance to cancer biology and treatment, immunology, metabolism, and autoimmunity.