Jonathan W. Simons is an American physician-scientist, medical oncologist, and leader in prostate cancer research. Simons’ laboratories at Johns Hopkins University and Emory University made original basic science contributions to understand the HIF-1 transcription factor in the molecular biology of cancer metastases and to defining the functions of immunomodulatory cytokines in prostate cancer bone metastases. Simons translational research program and young investigators in Simons’s laboratory proved the possibility of breaking pre-existing T-cell and B-cell immune tolerance to metastatic prostate cancer by using GM-CSF gene transduced prostate cancer vaccines in proof of concept clinical trials.