Joe W. Ramos, PhD
Joe W. Ramos, PhD
- Co-Director, Associate Professor
Cancer Biology Program
University of Hawaii Cancer Center
- Adjunct Associate Professor
Cell and Molecular Biology
John A. Burns School of Medicine, University of Hawaii at Manoa;
Molecular Biosciences and Bioengineering, University of Hawaii at Manoa
- PhD, Cell Biology
University of Virginia
Dr. Ramos's research focuses on understanding the underlying mechanisms that control cancer cell proliferation and metastasis. In particular, his interests include how regulation of the ERK MAP kinase pathway contributes to pathogenic behaviors.
As a first step, he used expression cloning to isolate proteins that interfere with ERK MAP kinase signaling to the cell adhesion proteins the integrins. One such protein is PEA-15. PEA-15 can alter ERK signaling to other proteins as well, including the transcription factor Elk1 and the kinase Rsk2.
PEA-15 is widely expressed throughout the body, with particularly high levels expressed in astrocytes and lymphocytes. The structure of PEA-15 is striking in that the N-terminal half of the protein consists of a conserved death effector domain. This domain is usually found in proteins involved in apoptosis. Indeed, PEA-15 prevents FADD-mediated apoptosis. The C-terminal half of the protein contains two phosphorylated serines that appear to regulate PEA-15 function. Dr Ramos' work has shown that PEA-15 binds directly to ERK and maintains it in the cytoplasm. Similarly, PEA-15 can also bind to Rsk2 and may therefore affect ERK activation of Rsk2 in the cytoplasm. By determining the location in the cell of these kinases PEA-15 can channel ERK signaling to cytoplasmic substrates to the exclusion of nuclear targets like the transcription factor ELK1 and thus modify the outcome of ERK activation.
Ramos and colleagues are using PEA-15 null mice and molecular and cell biological approaches to better understand the function of PEA-15. They have also begun to isolate and characterize related proteins. In collaboration with fellow chemists, they are developing new drugs to target cancer based on basic research findings. Currently they are examining the deregulation of cell signaling in neuroblastoma, glioma and breast cancer.
- Z. Liang, A. Sorribas, F.J. Sulzmaier, J.I. JimĂ©nez, X. Wang, T. Sauvage, W.Y. Yoshida, G.Wang, J.W. Ramos, and P.G. Williams. Stictamides A-C, 4-amino-3-hydroxy-4-phenylpentanoic acid containing MMP12 inhibitors. J.Org Chem, 76(10):3635-3643 (2011). PMCID: In process
- S. Pastorino, H. Renganathan, M. Caliva, E. Filbert, J. Opoku-Ansah, F.J. Sulzmaier, J.E. Gawecka, G. Werlen, A.S. Shaw and J.W. Ramos. The Death Effector Domain protein PEA-15 negatively regulates T cell receptor signaling. FASEB J, 24(8):2818-28 (2010). PMCID: PMC2909277
- J.E. Gawecka, G.S. Griffiths, B. Ek-Rylander, J.W. Ramos, and M.L. Matter. R-Ras regulates migration through an interaction with Filamin A in melanoma cells. PLoS ONE 5(6): e11269. doi:10.1371/journal.pone.0011269 (2010). PMCID: PMC2890414
- J.W. Ramos. (2008). The Regulation of Extracellular Signal-Regulated Kinase (ERK) in Mammalian Cells. IJBCB, 40(12):2707-2719.
- H. Vaidyanathan, J. Opoku-Ansah, S. Pastorino, H. Renganathan, M.L. Matter and J.W. Ramos. (2007). ERK MAP kinase is targeted to RSK2 by the phosphoprotein PEA-15. PNAS, 105(50):19837-19842.
Publication list via PubMed
- J.W. Ramos, Principal Investigator
"RSK-2 regulates integrin-mediated adhesion and migration"
- J.W. Ramos, Co-Principal Investigator (P.G. Williams, Principal Investigator)
The Victoria S. and Bradley L. Geist Foundation
"Ras/ERK MAP kinase inhibitors from marine sources"