University of Hawai‘i at Manoa Homepage
Hawaiian Fern

Joe W. Ramos, PhD

Joe W. Ramos, PhD

Joe W. Ramos, PhD
  • Program Director and Professor
    Cancer Biology Program
    University of Hawaii Cancer Center
  • Professor
    Cell Biology;
    Graduate Faculty
    Cell and Molecular Biology
    John A. Burns School of Medicine,
    University of Hawaii at Manoa;
    Molecular Biosciences and Bioengineering,
    University of Hawaii at Manoa

Degrees

  • PhD, Cell Biology
    University of Virginia

Research Focus

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.

Publications

  • F.J. Sulzmaier and J.W. Ramos. RSK isoforms in cancer cell invasion and metastasis. Cancer Res., Oct 15;73(20):6099-105. doi: 10.1158/0008-5472.CAN-13-1087. (2013) PMID: 24097826 PMCID: In Process
  • J.E. Gawecka, S.S. Young-Robbins, F.J. Sulzmaier, M.J. Caliva, M.M. Heikkilä, M.L. Matter, and J.W. Ramos. RSK2 protein suppresses integrin activation and fibronectin matrix assembly and promotes cell migration. J. Biol. Chem., 287: 43424-43437 (2012). PMCID: PMC3527930.
  • F.J. Sulzmaier, Z. Li, M.L. Nakashige, D.M. Fish, W.J. Chain, J.W. Ramos. Englerin A selectively induces necrosis in human renal cells. PLOS ONE, 7(10):e48032. doi:10.1371/journal.pone.0048032  (2012) PMCID: PMC3481555.
  • F.J. Sulzmaier, M.K. Gudur-Valmiki, M.J. Caliva, D.A. Nelson, D. Geerts, M.L. Matter, E.P. White and J.W. Ramos. PEA-15 enhances H-Ras mediated epithelial cell transformation through Phospholipase D. Oncogene 31(30):3547-60 (2012). PMCID: PMC3295902.
  • J.E. Gawecka, D. Geerts, J. Koster, M.J. Caliva, F.J. Sulzmaier, J. Opoku-Ansah, R.K. Wada, A.S. Bachmann, and J.W. Ramos. PEA-15 impairs cell migration and correlates with genetic and clinical features predicting good prognosis in neuroblastoma. International Journal of Cancer, 131(7):1556-68 (2011). PMCID: PMC3757132.
  • H. Vaidyanathan, J. Opoku-Ansah, S. Pastorino, H. Renganathan, M.L. Matter and J.W. Ramos. ERK MAP kinase is targeted to RSK2 by the phosphoprotein PEA-15. PNAS, 105(50):19837-19842 (2007). Direct Submission-Peer reviewed. PMCID: PMC2148384

Publication list via PubMed

Active Grants

  • J.W. Ramos, Principal Investigator
    RO1 GM088266-A1
    "RSK-2 regulates integrin-mediated adhesion and migration"
    2010-2014
  • J.W. Ramos, Principal Investigator
    ID# HCF44279
    The Ingeborg v.F. Mckee Fund
    "Molecular mechanisms underlying metastatic recurrence of
    neuroblastoma"
    2013-2014
  • 5R01CA096841-08 and -08S1 (parent grant and diversity supplement):
    "Regulation of Tumor Promotion by RASGRP1"
    08/02/02 - 04/30/16, (Multiple PIs)
  • 5R03CA165128-02
    "Ras activation pathways in UVR-induced epidermal transformation "
    12/01/11 - 11/30/13, (Multiple PIs)
Joomla16 Appliance - Powered by TurnKey Linux