Cellular Responses to Tumor-Derived Hormones and Growth Factors

Research Team:  Band, Bentram, Budunova, Bulun, Chakravarti, Clevenger, Jameson, Linzer, Lupu, Mayo, Pelling, Platanias, Rodriguez, Rosen, Stein, Woodruff

The levels and activities of ligands and receptors as well as their signaling intermediates are tightly regulated to ensure physiological responses. Alterations in these regulatory mechanisms can thereby deregulate cellular responses to hormone and growth factors, promoting oncogenic behavior. Members of the program are investigating the role of phosphorylation/dephosphorylation, ubiquitination and other post-translational modifications (Band, Bentram, Budunova, Bulun, Chakravarti, Clevenger, Jameson, Linzer, Lupu, Mayo, Pelling, Platanias, Rodriguez, Rosen, Stein, Woodruff), DNA- and histone ( chromatin)-based modifications such as methylation and acetylation (Bulun, Chakravarti, Clevenger, Jameson, Linzer, Lupu, Mayo, Platanias, Rosen, Woodruff) and other mechanisms that control the intensity and duration as well as the nature of signals downstream of productive ligand-receptor interactions, and how these control mechanisms are altered in neoplastic cells. In addition, subcellular trafficking events that control the proper localization of receptors and signaling proteins as well as their post-activation degradation through endocytic or proteasomal pathways are under active investigation (Band, Budunova, Bulun, Clevenger, Jameson, Linzer, Lupu, Mayo, Pelling, Platanias, Rosen, Stein, Woodruff). Insights derived from the identification of cellular pathways that endow a normal cell with the ability to process exogenous information into coordinated responses will permit a more comprehensive understanding of how these responses are altered in tumor cells. Importantly, these insights should help the investigators in designing translational efforts to target regulatory components of signaling pathways and also provide extended molecular signatures for molecular diagnosis and prediction of therapeutic responses.

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