Signal Transduction Pathways in Normal and Neoplastic Cells

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

Ligand-receptor interactions trigger a number of cytoplasmic as well as nuclear signaling pathways that directly control normal cellular functions, including cell proliferation and differentiation, cell cycle progression, apoptosis and cell migration. Consequently, aberrant signaling due to altered expression and/or mutational activation or inactivation of signaling proteins has emerged as key element of oncogenic transformation. The role of crucial signaling pathways such as MAPK, JNK/p38, PI 3-kinase and small G-proteins in normal and neoplastic signaling is being investigated by members of the program with a particular focus on hormonal regulation of developmental processes (Budunova, Clevenger, Jameson, Linzer, Mayo, Woodruff), signaling by protein kinases involved in solid tumor and leukemia/lymphoma pathogenesis (Band, Bentram, Freyman, Lupu, Mayo, Platanias, Pelling, Rosen, Stein, Woodruff), transcriptional and non-genomic mechanisms of nuclear hormone receptor function and its control by co-activators and co-repressors, and chromatin associated proteins (Budunova, Bulun, Chakravarti, Clevenger, Jameson, Mayo, Rodriguez, Rosen, Woodruff), in vivo genetic model systems to investigate tumor-relevant signaling mechanisms (Band, Budunova, Bulun, Mayo, Stein, Iwasaki, Woodruff,) and signaling pathways downstream of mutant signaling receptors or intermediates (Band, Jameson, Platanias, Rosen). By targeting the signal transduction pathways that are causally linked to abnormal growth, differentiation, migration and survival of a tumor cell, the oncogenic process can be halted, leading to the elimination of the tumor. Finally, in vitro and in vivo models to screen for inhibitors of specific oncogenic signaling pathways as well as to identify newer signaling components through genome-scale strategies are being developed by the program investigators (Band, Bulun, Chakravarti, Jameson, Pelling, Platanias, Rosen, Woodruff). Collectively, these studies will help elucidate how specific ligands regulate cellular responses, elucidate how aberrations of signaling pathways may play a vital role in the pathogenesis of cancer and other human diseases, identify signaling mechanisms that can be targeted in neoplastic cells, and help develop model systems for high-throughput screening for new inhibitors of signaling pathways for therapeutics development.

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