Monday 8th September 2008
John Condeelis, PhD
John Condeelis is Professor and co-Chairman of the Department of Anatomy and Structural Biology at the Albert Einstein College of Medicine (AECOM). He is the director of the Cancer Center program “Tumor microenvironment and metastasis” and co-Director, with Robert Singer, of the Gruss Lipper Biophotonics Center of AECOM, a center dedicated to the development and application of optical imaging technologies. His training is in nuclear physics, optical physics and cell biology. He worked for the US Navy on particle accelerators and wave guides, and was a PhD student of Robert Allen, the developer of video microscope imaging, with whom he learned live cell microscopy and polarized optics. His current research interest is in tumor cell motility, chemotaxis and invasion during metastasis. He has pioneered the use of combined multiphoton imaging with expression analysis to derive gene expression signatures that define the pathways used by tumor cells in mammary tumors to move and invade blood vessels. He discovered the Invasion Signature of breast tumors. He has devised optical microscopes for uncaging, biosensor detection and multiphoton imaging for these studies and has used novel caged-enzymes and biosensors to test, in vivo, the predictions of the invasion signature regarding the mechanisms of tumor cell chemotaxis to EGF. He has authored more than 200 scientific papers on various aspects of cell and cancer biology, and optical imaging. He has held elected office in national societies including President of the New York Society of Experimental Microscopists, 2006-2009 Council of the American Society of Cell Biology, and 2006-2007 Centennial Program Committee of the American Association of Cancer Research. He has served on numerous study sections at NIH and the ACS and as Chairman of the Physiology and Cell Biology Study Section, the Gordon Conference on Motile Systems, and the Board of Scientific Councilors of the Heart, Lung and Blood Institute at NIH. He has served on editorial boards of prominent journals including Journal of Cell Biology. His honors include the Allen Foundation Scholar Award, the Hirschl Career Scientist Award, and election as a fellow of the American Association for the Advancement of Science. He has served as a consultant to the NCI for planning 3 programs: 1.Tumor Microenvironment, 2.Tumor cell dormancy and 3.Tumor Metastasis.
High resolution optical in vivo imaging of tumor cell motility, chemotaxis, invasion and metastasis in breast tumors
John Condeelis, PhD
The recent convergence of technologies for expression profiling and multi-photon based intravital imaging has revealed the behavior of individual tumor cells in mammary tumors in vivo, and the identities of the genes involved in the survival, adjuvant-resistance and chemotaxis of invasive cancer cells in vivo. These genes fall into well defined pathways and are coordinately regulated in invasive tumor cells. This pattern is called the Invasion Signature. The Invasion Signature indicates that invasive cancer cells are a population that is neither proliferating nor apoptotic but highly chemotactic to macrophage-secreted EGF. Of particular relevance to the migratory behavior of invasive cancer cells is the finding that the genes coding for pathways leading to chemotaxis and invadopod formation are up-regulated. Several pathways of the Invasion Signature are particularly relevant to the contribution of the tumor microenvironment to metastasis because 1) they describe the molecular basis of chemotaxis to blood vessels as it is involved in the escape of cancer cells from primary mammary tumors, and 2) these pathways contain makers that can be used to define the microenvironment of metastasis including the stromal cells that support tumor cell invasion and intravasation. Key genes in the Invasion Signature have been studied for their ability to alter metastatic outcome and these results confirm the importance of the Invasion Signature in predicting metastasis. The Invasion Signature predicts that invasive tumor cells, upon escaping the primary tumor, are non-dividing and resistant to chemotherapy, predictions that have been confirmed in animal models using high resolution optical intravital imaging. The Invasion Signature provides several new target opportunities both as biomarkers for predicting prognosis and as therapeutic targets.
Wang, Goswami, Sahai, Wyckoff, Segall, Condeelis (2005) Tumor Cells caught in the act of invading: How they revealed their strategy for enhanced cell motility. Trends Cell Biol. 15:138-145.
Condeelis, Singer and Segall (2005) The great escape: When cancer cells hijack the genes for chemotaxis and motility. Annual Rev. Cell and Developmental Biology. 21:695-718.
Condeelis and Pollard (2006) Macrophages: obligate partners for tumor cell migration, invasion and metastasis. Cell 124:263-266.
Wyckoff , Wang, Lin, Li, Goswami, Stanley, Segall, Pollard, and Condeelis (2007) Direct visualization of macrophage mediated tumor cell intravasation in mammary tumors. Cancer Research. 67:2649-56.
Wang, Eddy, and Condeelis (2007) The cofilin pathway in mammary tumor invasion and metastasis. Nature Reviews Cancer 7:429-440.