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Ramos, Joe
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overview
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My lab’s mission is to determine the underlying mechanisms that control cancer cell invasion and to exploit this knowledge in drug development. Currently we are examining the dysregulation of cell signaling in glioblastoma, skin cancer, and kidney cancer and developing drugs to block growth and invasion of these tumors. Because of my research, we better understand how cell adhesion mechanisms drive developmental and pathological processes and have validated some of these mechanisms as targets for novel therapeutic interventions. Working with collaborators I have identified important spatio-temporal regulation of integrin mediated cell adhesion and signaling during gastrulation and muscle development. I elucidated underlying mechanisms mediating adhesion changes during epithelial to mesenchymal transitions. Our work on the signaling that regulates adhesive changes led to the identification of the death effector domain containing protein PEA-15 as a potent regulator of ERK1/2 and thereby integrin activity. We further identified ERK-dependent physiological and pathological effects of PEA-15. In examining the molecular mechanisms by which PEA15 works we found that it also interacts with the kinase RSK2 and acts as a scaffold to direct ERK to RSK2 and enhance RSK2 activity. We defined RSK2 as a primary mediator of Ras signals to integrins and an essential regulator of integrin activation and cell migration. Finally, in our collaborations with chemists we have developed new anti-cancer drug leads (GBM and Kidney) from organometallic and natural product structures.
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