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My current research interests, which I share with my wife and scientific partner, Dr. Vera Donnenberg, focus on cancer stem cells and their role in tumorigenesis, invasion and metastasis. We view stemness in epithelial cancers as a state rather than the property of a unique cell type, with individual tumor cells transiting in and out of the cancer stem cell state. According to this interpretation, the more aggressive the tumor, the more cells exist in the stem-like state at any given time. In xenograft models, tumorigenicity is dependent on this state, which can be recognized by the expression of a number of markers that are associated with normal mesenchymal stem cells. In epithelial cancers mesenchymal markers are associated with invasion, immune suppression and drug resistance. Taken together, the cancer stem cell paradigm has converged with the bidirectional epithelial to mesenchymal/mesenchymal to epithelial transitions (EMT/MET). Our working hypothesis is that neoplastic transformation and conferral of invasiveness are often independent processes, the later on wound-healing signals present in the tumor microenvironment. Thus, a carcinoma in situ and an invasive carcinoma may share a common mutational profile but exist in very different microenvironments. Since the environment is controlled to a large part by tissue macrophages and stromal cells, which interact at close distances with tumor cells, our research efforts are currently aimed at understanding how polarization toward wound healing influences tumor cell behavior, and how tumor cells influence polarization.
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