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Joe Ramos, PhD

TitleDeputy Director
Faculty RankProfessor
InstitutionUniversity of Hawaii
DepartmentCancer Biology
AddressUniversity of Hawaii Cancer Center
701 Ilalo Street
B-620
Honolulu HI 96813
Phone8085645843
Fax8085870742
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    Collapse Overview 
    Collapse overview
    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.

    Collapse Research 
    Collapse research activities and funding
    F32CA074529     (RAMOS, JOE WILLIAM)Oct 31, 1997
    NIH
    INTEGRIN CYTOPLASMIC DOMAIN FUNCTION IN FIBRONECTIN
    Role: Principal Investigator

    R01CA093849     (RAMOS, JOE WILLIAM)Jul 1, 2002 - Jun 30, 2007
    NIH
    Regulation of Cell Signaling and Adhesion
    Role: Principal Investigator

    R56CA093849     (RAMOS, JOE WILLIAM)Jul 1, 2002 - Aug 31, 2008
    NIH
    Regulation of Cell Signaling and Adhesion
    Role: Principal Investigator

    R01CA096841     (RAMOS, JOE WILLIAM)Aug 1, 2002 - Apr 30, 2017
    NIH
    Regulation of tumor promotion by RasGRP1
    Role: Principal Investigator

    R01GM088266     (RAMOS, JOE WILLIAM)Sep 30, 2010 - Aug 31, 2015
    NIH
    RSK-2 regulates integrin-mediated adhesion and migration
    Role: Principal Investigator

    R03CA165128     (RAMOS, JOE WILLIAM)Dec 1, 2011 - Nov 30, 2014
    NIH
    Ras activation pathways in UVR-induced epidermal transformation
    Role: Principal Investigator

    R25CA244073     (MASKARINEC, GERTRAUD)Aug 1, 2020 - Jul 31, 2025
    NIH
    Cancer Research Education, Advancement, Training and Empowerment (CREATE) in the Pacific
    Role: Co-Principal Investigator

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Shi GX, Yang WS, Jin L, Matter ML, Ramos JW. RSK2 drives cell motility by serine phosphorylation of LARG and activation of Rho GTPases. Proc Natl Acad Sci U S A. 2018 01 09; 115(2):E190-E199. PMID: 29279389.
      Citations: 21     Fields:    Translation:HumansCells
    2. Greig FH, Kennedy S, Gibson G, Ramos JW, Nixon GF. PEA-15 (Phosphoprotein Enriched in Astrocytes 15) Is a Protective Mediator in the Vasculature and Is Regulated During Neointimal Hyperplasia. J Am Heart Assoc. 2017 Sep 11; 6(9). PMID: 28893763.
      Citations: 6     Fields:    Translation:HumansAnimalsCells
    3. Doe J, Kaindl AM, Jijiwa M, de la Vega M, Hu H, Griffiths GS, Fontelonga TM, Barraza P, Cruz V, Van Ry P, Ramos JW, Burkin DJ, Matter ML. PTRH2 gene mutation causes progressive congenital skeletal muscle pathology. Hum Mol Genet. 2017 04 15; 26(8):1458-1464. PMID: 28175314.
      Citations: 6     Fields:    Translation:HumansAnimalsCells
    4. Sulzmaier FJ, Young-Robbins S, Jiang P, Geerts D, Prechtl AM, Matter ML, Kesari S, Ramos JW. RSK2 activity mediates glioblastoma invasiveness and is a potential target for new therapeutics. Oncotarget. 2016 Nov 29; 7(48):79869-79884. PMID: 27829215.
      Citations: 19     Fields:    Translation:HumansAnimalsCells
    5. Jorand R, Biswas S, Wakefield DL, Tobin SJ, Golfetto O, Hilton K, Ko M, Ramos JW, Small AR, Chu P, Singh G, Jovanovic-Talisman T. Molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer. Mol Biol Cell. 2016 11 07; 27(22):3659-3672. PMID: 27682590.
      Citations: 14     Fields:    Translation:HumansCells
    6. Fash DM, Peer CJ, Li Z, Talisman IJ, Hayavi S, Sulzmaier FJ, Ramos JW, Sourbier C, Neckers L, Figg WD, Beutler JA, Chain WJ. Synthesis of a stable and orally bioavailable englerin analogue. Bioorg Med Chem Lett. 2016 06 01; 26(11):2641-4. PMID: 27107948.
      Citations: 7     Fields:    Translation:HumansAnimalsCells
    7. Fern?ndez-Gallardo J, Elie BT, Sadhukha T, Prabha S, Sana? M, Rotenberg SA, Ramos JW, Contel M. Heterometallic titanium-gold complexes inhibit renal cancer cells in vitro and in vivo. Chem Sci. 2015 Sep 01; 6(9):5269-5283. PMID: 27213034.
      Citations:    
    8. Griffiths GS, Doe J, Jijiwa M, Van Ry P, Cruz V, de la Vega M, Ramos JW, Burkin DJ, Matter ML. Bit-1 is an essential regulator of myogenic differentiation. J Cell Sci. 2015 May 01; 128(9):1707-17. PMID: 25770104.
      Citations: 11     Fields:    Translation:AnimalsCells
    9. Liang Z, Sulzmaier FJ, Yoshida WY, Kelly M, Ramos JW, Williams PG. Neopetrocyclamines A and B, polycyclic diamine alkaloids from the sponge Neopetrosia cf exigua. J Nat Prod. 2015 Mar 27; 78(3):543-7. PMID: 25585025.
      Citations: 6     Fields:    Translation:HumansAnimalsCells
    10. Frik M, Mart?nez A, Elie BT, Gonzalo O, Ram?rez de Mingo D, Sana? M, S?nchez-Delgado R, Sadhukha T, Prabha S, Ramos JW, Marzo I, Contel M. In vitro and in vivo evaluation of water-soluble iminophosphorane ruthenium(II) compounds. A potential chemotherapeutic agent for triple negative breast cancer. J Med Chem. 2014 Dec 11; 57(23):9995-10012. PMID: 25409416.
      Citations: 19     Fields:    Translation:HumansAnimalsCells
    11. Fern?ndez-Gallardo J, Elie BT, Sulzmaier FJ, Sana? M, Ramos JW, Contel M. Organometallic Titanocene-Gold Compounds as Potential Chemotherapeutics in Renal Cancer. Study of their Protein Kinase Inhibitory Properties. Organometallics. 2014 Nov 24; 33(22):6669-6681. PMID: 25435644.
      Citations:    
    12. Sharma A, Fonseca LL, Rajani C, Yanagida JK, Endo Y, Cline JM, Stone JC, Ji J, Ramos JW, Lorenzo PS. Targeted deletion of RasGRP1 impairs skin tumorigenesis. Carcinogenesis. 2014 May; 35(5):1084-91. PMID: 24464785.
      Citations: 9     Fields:    Translation:Animals
    13. Sulzmaier FJ, Ramos JW. RSK isoforms in cancer cell invasion and metastasis. Cancer Res. 2013 Oct 15; 73(20):6099-105. PMID: 24097826.
      Citations: 55     Fields:    Translation:HumansAnimalsCells
    14. Gawecka JE, Young-Robbins SS, Sulzmaier FJ, Caliva MJ, Heikkil? MM, Matter ML, Ramos JW. RSK2 protein suppresses integrin activation and fibronectin matrix assembly and promotes cell migration. J Biol Chem. 2012 Dec 21; 287(52):43424-37. PMID: 23118220.
      Citations: 32     Fields:    Translation:HumansAnimalsCells
    15. Sulzmaier FJ, Li Z, Nakashige ML, Fash DM, Chain WJ, Ramos JW. Englerin a selectively induces necrosis in human renal cancer cells. PLoS One. 2012; 7(10):e48032. PMID: 23144724.
      Citations: 16     Fields:    Translation:HumansCells
    16. Sulzmaier F, Opoku-Ansah J, Ramos JW. Phosphorylation is the switch that turns PEA-15 from tumor suppressor to tumor promoter. Small GTPases. 2012 Jul-Sep; 3(3):173-7. PMID: 22694972.
      Citations: 23     Fields:    Translation:HumansAnimalsCells
    17. Gawecka JE, Geerts D, Koster J, Caliva MJ, Sulzmaier FJ, Opoku-Ansah J, Wada RK, Bachmann AS, Ramos JW. PEA15 impairs cell migration and correlates with clinical features predicting good prognosis in neuroblastoma. Int J Cancer. 2012 Oct 01; 131(7):1556-68. PMID: 22213050.
      Citations: 10     Fields:    Translation:HumansAnimalsCells
    18. Sulzmaier FJ, Valmiki MK, Nelson DA, Caliva MJ, Geerts D, Matter ML, White EP, Ramos JW. PEA-15 potentiates H-Ras-mediated epithelial cell transformation through phospholipase D. Oncogene. 2012 Jul 26; 31(30):3547-60. PMID: 22105357.
      Citations: 21     Fields:    Translation:HumansAnimalsCells
    19. Liang Z, Sorribas A, Sulzmaier FJ, Jim?nez JI, Wang X, Sauvage T, Yoshida WY, Wang G, Ramos JW, Williams PG. Stictamides A-C, MMP12 inhibitors containing 4-amino-3-hydroxy-5-phenylpentanoic acid subunits. J Org Chem. 2011 May 20; 76(10):3635-43. PMID: 21500817.
      Citations: 6     Fields:    Translation:HumansCells
    20. Griffiths GS, Grundl M, Leychenko A, Reiter S, Young-Robbins SS, Sulzmaier FJ, Caliva MJ, Ramos JW, Matter ML. Bit-1 mediates integrin-dependent cell survival through activation of the NFkappaB pathway. J Biol Chem. 2011 Apr 22; 286(16):14713-23. PMID: 21383007.
      Citations: 25     Fields:    Translation:HumansAnimalsCells
    21. Hunter I, Mascall KS, Ramos JW, Nixon GF. A phospholipase C?1-activated pathway regulates transcription in human vascular smooth muscle cells. Cardiovasc Res. 2011 Jun 01; 90(3):557-64. PMID: 21285289.
      Citations: 8     Fields:    Translation:HumansCells
    22. Gawecka JE, Griffiths GS, Ek-Rylander B, Ramos JW, Matter ML. R-Ras regulates migration through an interaction with filamin A in melanoma cells. PLoS One. 2010 Jun 23; 5(6):e11269. PMID: 20585650.
      Citations: 34     Fields:    Translation:HumansCells
    23. Pastorino S, Renganathan H, Caliva MJ, Filbert EL, Opoku-Ansah J, Sulzmaier FJ, Gawecka JE, Werlen G, Shaw AS, Ramos JW. The death effector domain protein PEA-15 negatively regulates T-cell receptor signaling. FASEB J. 2010 Aug; 24(8):2818-28. PMID: 20354143.
      Citations: 15     Fields:    Translation:HumansAnimalsCells
    24. Ramos JW, Townsend DA, Piarulli D, Kolata S, Light K, Hale G, Matzel LD. Deletion of PEA-15 in mice is associated with specific impairments of spatial learning abilities. BMC Neurosci. 2009 Nov 16; 10:134. PMID: 19917132.
      Citations: 7     Fields:    Translation:Animals
    25. Valmiki MG, Ramos JW. Death effector domain-containing proteins. Cell Mol Life Sci. 2009 Mar; 66(5):814-30. PMID: 18989622.
      Citations: 42     Fields:    Translation:HumansAnimalsCells
    26. Ramos JW. The regulation of extracellular signal-regulated kinase (ERK) in mammalian cells. Int J Biochem Cell Biol. 2008; 40(12):2707-19. PMID: 18562239.
      Citations: 207     Fields:    Translation:HumansAnimalsCells
    27. Pastorino S, Ramos JW. Glioma: challenges and new insights in the development of effective therapies. Hawaii Med J. 2008 Jan; 67(1):20-3, 25. PMID: 18309836.
      Citations:    Fields:    Translation:HumansAnimals
    28. Vaidyanathan H, Opoku-Ansah J, Pastorino S, Renganathan H, Matter ML, Ramos JW. ERK MAP kinase is targeted to RSK2 by the phosphoprotein PEA-15. Proc Natl Acad Sci U S A. 2007 Dec 11; 104(50):19837-42. PMID: 18077417.
      Citations: 31     Fields:    Translation:HumansAnimalsCells
    29. Renault-Mihara F, Beuvon F, Iturrioz X, Canton B, De Bouard S, L?onard N, Mouhamad S, Sharif A, Ramos JW, Junier MP, Chneiweiss H. Phosphoprotein enriched in astrocytes-15 kDa expression inhibits astrocyte migration by a protein kinase C delta-dependent mechanism. Mol Biol Cell. 2006 Dec; 17(12):5141-52. PMID: 16987961.
      Citations: 18     Fields:    Translation:HumansAnimalsCells
    30. Matter ML, Ramos JW. Expression cloning of signaling proteins regulated by cell adhesion. Methods Mol Biol. 2006; 341:155-65. PMID: 16799197.
      Citations:    Fields:    Translation:AnimalsCells
    31. Renganathan H, Vaidyanathan H, Knapinska A, Ramos JW. Phosphorylation of PEA-15 switches its binding specificity from ERK/MAPK to FADD. Biochem J. 2005 Sep 15; 390(Pt 3):729-35. PMID: 15916534.
      Citations: 46     Fields:    Translation:HumansAnimalsCells
    32. Sur R, Ramos JW. Vanishin is a novel ubiquitinylated death-effector domain protein that blocks ERK activation. Biochem J. 2005 Apr 15; 387(Pt 2):315-24. PMID: 15537391.
      Citations: 2     Fields:    Translation:HumansAnimalsCells
    33. Ramos JW. Cancer research center hotline: PEA-15 phosphoprotein: a potential cancer drug target. Hawaii Med J. 2005 Mar; 64(3):77-80. PMID: 15892267.
      Citations: 4     Fields:    Translation:Humans
    34. Chou FL, Hill JM, Hsieh JC, Pouyssegur J, Brunet A, Glading A, Uberall F, Ramos JW, Werner MH, Ginsberg MH. PEA-15 binding to ERK1/2 MAPKs is required for its modulation of integrin activation. J Biol Chem. 2003 Dec 26; 278(52):52587-97. PMID: 14506247.
      Citations: 28     Fields:    Translation:AnimalsCells
    35. Vaidyanathan H, Ramos JW. RSK2 activity is regulated by its interaction with PEA-15. J Biol Chem. 2003 Aug 22; 278(34):32367-72. PMID: 12796492.
      Citations: 28     Fields:    Translation:HumansAnimalsCells
    36. Hill JM, Vaidyanathan H, Ramos JW, Ginsberg MH, Werner MH. Recognition of ERK MAP kinase by PEA-15 reveals a common docking site within the death domain and death effector domain. EMBO J. 2002 Dec 02; 21(23):6494-504. PMID: 12456656.
      Citations: 36     Fields:    Translation:AnimalsCells
    37. Ramos JW, Ginsberg M. Expression cloning strategies for the identification of adhesion molecules. Methods Cell Biol. 2002; 69:209-21. PMID: 12070994.
      Citations: 1     Fields:    Translation:AnimalsCells
    38. Matter ML, Ginsberg MH, Ramos JW. Identification of cell signaling molecules by expression cloning. Sci STKE. 2001 Oct 09; 2001(103):pl9. PMID: 11593050.
      Citations: 2     Fields:    Translation:AnimalsCells
    39. Formstecher E, Ramos JW, Fauquet M, Calderwood DA, Hsieh JC, Canton B, Nguyen XT, Barnier JV, Camonis J, Ginsberg MH, Chneiweiss H. PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase. Dev Cell. 2001 Aug; 1(2):239-50. PMID: 11702783.
      Citations: 134     Fields:    Translation:AnimalsCells
    40. Zhang Y, Redina O, Altshuller YM, Yamazaki M, Ramos J, Chneiweiss H, Kanaho Y, Frohman MA. Regulation of expression of phospholipase D1 and D2 by PEA-15, a novel protein that interacts with them. J Biol Chem. 2000 Nov 10; 275(45):35224-32. PMID: 10926929.
      Citations: 24     Fields:    Translation:HumansAnimalsCells
    41. Ramos JW, Hughes PE, Renshaw MW, Schwartz MA, Formstecher E, Chneiweiss H, Ginsberg MH. Death effector domain protein PEA-15 potentiates Ras activation of extracellular signal receptor-activated kinase by an adhesion-independent mechanism. Mol Biol Cell. 2000 Sep; 11(9):2863-72. PMID: 10982386.
      Citations: 26     Fields:    Translation:HumansAnimalsCells
    42. Ramos JW, Kojima TK, Hughes PE, Fenczik CA, Ginsberg MH. The death effector domain of PEA-15 is involved in its regulation of integrin activation. J Biol Chem. 1998 Dec 18; 273(51):33897-900. PMID: 9852038.
      Citations: 34     Fields:    Translation:AnimalsCells
    43. Fenczik CA, Sethi T, Ramos JW, Hughes PE, Ginsberg MH. Complementation of dominant suppression implicates CD98 in integrin activation. Nature. 1997 Nov 06; 390(6655):81-5. PMID: 9363894.
      Citations: 85     Fields:    Translation:HumansAnimalsCells
    44. Ramos JW, Whittaker CA, DeSimone DW. Integrin-dependent adhesive activity is spatially controlled by inductive signals at gastrulation. Development. 1996 Sep; 122(9):2873-83. PMID: 8787760.
      Citations: 22     Fields:    Translation:AnimalsCells
    45. Ramos JW, DeSimone DW. Xenopus embryonic cell adhesion to fibronectin: position-specific activation of RGD/synergy site-dependent migratory behavior at gastrulation. J Cell Biol. 1996 Jul; 134(1):227-40. PMID: 8698817.
      Citations: 36     Fields:    Translation:AnimalsCells
    46. Alfandari D, Ramos J, Clavilier L, DeSimone DW, Darrib?re T. The RGD-dependent and the Hep II binding domains of fibronectin govern the adhesive behaviors of amphibian embryonic cells. Mech Dev. 1996 May; 56(1-2):83-92. PMID: 8798149.
      Citations:    Fields:    Translation:AnimalsCells
    47. Danker K, Hacke H, Ramos J, DeSimone D, Wedlich D. V(+)-fibronectin expression and localization prior to gastrulation in Xenopus laevis embryos. Mech Dev. 1993 Dec; 44(2-3):155-65. PMID: 8155578.
      Citations: 6     Fields:    Translation:AnimalsCells
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