John Condeelis' research interests are in optical physics, cell biology and biophysics, cancer biology and mouse models of cancer. He and his collaborators developed the multiphoton imaging technology and animal models used to identify invasion and dissemination micro-environments in breast, pancreas and lung carcinoma. Integration of intravital multiphoton imaging with computational /systems analysis of living breast tumors identified the dominant tumor cell phenotypes contributing to invasion and dissemination during metastasis. This led to the discovery and verification of the paracrine interaction between tumor cells and macrophages in vivo, the role of macrophages in the migration of tumor cells during HGF-dependent tumor cell streaming to blood vessels and the mechanism of tumor cell dissemination from primary tumors via TMEM (Tumor MicroEnvironment of Metastasis) doorways to distant metastatic sites, and from those metastatic sites. Based on these results, cell collection techniques, including the in vivo invasion assay were developed for the collection of migrating and disseminating macrophages and tumor cells. This led to the discovery of the mouse and human invasion signatures, and the TMEM doorway, MenaCalc and MenaINV markers for assessing risk of metastasis and prediction of response in breast cancer patients to both chemotherapy, and receptor tyrosine kinase and tyrosine kinase inhibitors used to suppress metastasis.
He also helped lead the effort to develop a TMEM-activity-MRI for use in standard of care MRI prognosis of breast cancer patients. He is one of the founding co-directors of the Integrated Imaging Program dedicated to the integration and validation of clinical imaging platforms, including digital pathology, with high resolution optical imaging in the Gruss Lipper Biophotonics Center. He has authored more than 350 scientific papers on various aspects of his research.