My laboratory investigates how oncogenes initiate and sustain tumorigenesis. I have developed model systems whereby I can conditionally activate oncogenes in normal human and mouse cells in tissue culture or in specific tissues of transgenic mice. In particular using the tetracycline regulatory system, I have generated a conditional model system for MYC-induced tumors. I have shown that cancers caused by the conditional over-expression of the MYC proto-oncogene regress with its inactivation. Thus, even though cancer is a multi-step process, the inactivation of one oncogene can be sufficient to induce tumor regression. Now, I am using these model systems to address three questions:

1. How do oncogenes initiate tumorigenesis?
2. How does oncogene inactivation cause tumor regression?
3. How do tumors escape dependence on oncogenes?

• Wu CH, van Riggelen J, Yetil A, Fan AC, Bachireddy P, Felsher DW "Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation." Proc Natl Acad Sci U S A 2007; More
• Ray S, Atkuri KR, Deb-Basu D, Adler AS, Chang HY, Herzenberg LA, Felsher DW "MYC Can Induce DNA Breaks In vivo and In vitro Independent of Reactive Oxygen Species." Cancer Res 2006; 66: 13: 6598-6605 More
• Giuriato S, Ryeom S, Fan AC, Bachireddy P, Lynch RC, Rioth MJ, van Riggelen J, Kopelman AM, Passegué E, Tang F, Folkman J, Felsher DW "Sustained regression of tumors upon MYC inactivation requires p53 or thrombospondin-1 to reverse the angiogenic switch." Proc Natl Acad Sci U S A 2006; More
• Shachaf CM, Kopelman AM, Arvanitis C, Karlsson A, Beer S, Mandl S, Bachmann MH, Borowsky AD, Ruebner B, Cardiff RD, Yang Q, Bishop JM, Contag CH, Felsher DW "MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer." Nature 2004; More
• Beer S, Zetterberg A, Ihrie RA, McTaggart RA, Yang Q, Bradon N, Arvanitis C, Attardi LD, Feng S, Ruebner B, Cardiff RD, Felsher DW "Developmental Context Determines Latency of MYC-Induced Tumorigenesis." PLoS Biol 2004; 2: 11: E332 More