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Scott T. Eblen

Title
InstitutionMedical University of South Carolina
DepartmentCell and Molecular Pharmacology and Experimental Therapeutics
AddressP.O. Box MSC 509
BSB 313F
Basic Science Building - 173 Ashley Ave.
Phone843-792-8367
Fax843-792-9588
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    Collapse Overview 
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    Research in the Eblen lab focuses on the roles of serine-threonine protein kinases in cancer biology, particularly in ovarian and breast cancer. The research is primarily focused on the MAP kinase family, which regulate a number of cellular processes throughout the cell, including proliferation, migration, gene expression and drug resistance. These diverse roles are carried out by phosphorylation of dozens of target proteins throughout the cell. Changes in gene expression and kinase activation can greatly affect the biology of cancer cells. Areas of research interest include identification of novel MAP kinase substrates, regulation of MAP kinase activation by cellular adhesion and biological outcomes of signaling events.

    The laboratory uses a bioengineered system to identify novel MAP kinase substrates through use of a mutant MAP kinase that has been designed to uniquely utilize analogs of ATP. This method allows for the specific labeling of direct substrates of MAP kinases in a complex mixture of proteins, followed by the identification of the substrates by mass spectrometry. The laboratory has identified novel targets of the MAP kinase ERK2, some of which may have specific implications for ovarian cancer. In addition, similar mutants of p38 are used in a mouse model system of breast cancer to determine substrates of p38 involved in breast cancer progression.

    Another research interest in the lab is the regulation of MAP Kinase activation by cellular adhesion, which is important for anchorage independent growth and metastasis. We have uncovered some novel aspects of this regulation specific to ovarian cancer cell lines and are currently characterizing them. These mechanisms appear to be involved in the acquisition of anchorage-independent growth of ovarian cancer cells, which could have implications for cell survival and proliferation in peritoneal ascites fluid.

    Multicellular spheroids in the ascites fluid of ovarian cancer patients represent a population of cells that increase intraperitoneal metastasis and exhibit greater resistance to chemotherapeutic agents. The laboratory has a focus in determining how protein kinase signaling in spheroids regulates acquired drug resistance. The goal of this work is to develop novel therapeutic interventions in kinase signaling pathways for the treatment of ovarian cancer.
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    Signal Transduction in Cancer Biology

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    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.
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    1. Williams CB, Phelps-Polirer K, Dingle IP, Williams CJ, Rhett MJ, Eblen ST, Armeson K, Hill EG, Yeh ES. Correction: HUNK phosphorylates EGFR to regulate breast cancer metastasis. Oncogene. 2021 May; 40(20):3635-3636. PMID: 33958726.
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    2. Zambrano JN, Eblen ST, Abt M, Rhett JM, Muise-Helmericks R, Yeh ES. HUNK Phosphorylates Rubicon to Support Autophagy. Int J Mol Sci. 2019 Nov 19; 20(22). PMID: 31752345.
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    3. Williams CB, Phelps-Polirer K, Dingle IP, Williams CJ, Rhett MJ, Eblen ST, Armeson K, Hill EG, Yeh ES. HUNK phosphorylates EGFR to regulate breast cancer metastasis. Oncogene. 2020 01; 39(5):1112-1124. PMID: 31597954.
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    4. Kaur J, Daoud A, Eblen ST. Targeting Chromatin Remodeling for Cancer Therapy. Curr Mol Pharmacol. 2019; 12(3):215-229. PMID: 30767757.
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    5. Zambrano JN, Williams CJ, Williams CB, Hedgepeth L, Burger P, Dilday T, Eblen ST, Armeson K, Hill EG, Yeh ES. Staurosporine, an inhibitor of hormonally up-regulated neu-associated kinase. Oncotarget. 2018 Nov 13; 9(89):35962-35973. PMID: 30542510.
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    6. Eblen ST. Extracellular-Regulated Kinases: Signaling From Ras to ERK Substrates to Control Biological Outcomes. Adv Cancer Res. 2018; 138:99-142. PMID: 29551131.
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    7. Eblen ST, Bradley A. MOAP-1, UBR5 and cisplatin resistance in ovarian cancer. Transl Cancer Res. 2017 Feb; 6(Suppl 1):S18-S21. PMID: 29607295.
      View in: PubMed
    8. Collier JB, Whitaker RM, Eblen ST, Schnellmann RG. Rapid Renal Regulation of Peroxisome Proliferator-activated Receptor ? Coactivator-1a by Extracellular Signal-Regulated Kinase 1/2 in Physiological and Pathological Conditions. J Biol Chem. 2016 Dec 23; 291(52):26850-26859. PMID: 27875304.
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    9. Bradley A, Zheng H, Ziebarth A, Sakati W, Branham-O'Connor M, Blumer JB, Liu Y, Kistner-Griffin E, Rodriguez-Aguayo C, Lopez-Berestein G, Sood AK, Landen CN, Eblen ST. EDD enhances cell survival and cisplatin resistance and is a therapeutic target for epithelial ovarian cancer. Carcinogenesis. 2014 May; 35(5):1100-9. PMID: 24379240.
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    10. Ali MW, Cacan E, Liu Y, Pierce JY, Creasman WT, Murph MM, Govindarajan R, Eblen ST, Greer SF, Hooks SB. Transcriptional suppression, DNA methylation, and histone deacetylation of the regulator of G-protein signaling 10 (RGS10) gene in ovarian cancer cells. PLoS One. 2013; 8(3):e60185. PMID: 23533674.
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    11. Liu Y, Conaway L, Rutherford Bethard J, Al-Ayoubi AM, Thompson Bradley A, Zheng H, Weed SA, Eblen ST. Phosphorylation of the alternative mRNA splicing factor 45 (SPF45) by Clk1 regulates its splice site utilization, cell migration and invasion. Nucleic Acids Res. 2013 May; 41(9):4949-62. PMID: 23519612.
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    12. Mueller KL, Powell K, Madden JM, Eblen ST, Boerner JL. EGFR Tyrosine 845 Phosphorylation-Dependent Proliferation and Transformation of Breast Cancer Cells Require Activation of p38 MAPK. Transl Oncol. 2012 Oct; 5(5):327-34. PMID: 23066441.
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    13. Gault CR, Eblen ST, Neumann CA, Hannun YA, Obeid LM. Oncogenic K-Ras regulates bioactive sphingolipids in a sphingosine kinase 1-dependent manner. J Biol Chem. 2012 Sep 14; 287(38):31794-803. PMID: 22833671.
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    14. Al-Ayoubi AM, Zheng H, Liu Y, Bai T, Eblen ST. Mitogen-activated protein kinase phosphorylation of splicing factor 45 (SPF45) regulates SPF45 alternative splicing site utilization, proliferation, and cell adhesion. Mol Cell Biol. 2012 Jul; 32(14):2880-93. PMID: 22615491.
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    15. Eblen ST. Regulation of chemoresistance via alternative messenger RNA splicing. Biochem Pharmacol. 2012 Apr 15; 83(8):1063-72. PMID: 22248731.
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    16. Bethard JR, Zheng H, Roberts L, Eblen ST. Identification of phosphorylation sites on the E3 ubiquitin ligase UBR5/EDD. J Proteomics. 2011 Dec 21; 75(2):603-9. PMID: 21924388.
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    17. Li Q, Wu J, Zheng H, Liu K, Guo TL, Liu Y, Eblen ST, Grant S, Zhang S. Discovery of 3-(2-aminoethyl)-5-(3-phenyl-propylidene)-thiazolidine-2,4-dione as a dual inhibitor of the Raf/MEK/ERK and the PI3K/Akt signaling pathways. Bioorg Med Chem Lett. 2010 Aug 01; 20(15):4526-30. PMID: 20580230.
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    18. Zheng H, Al-Ayoubi A, Eblen ST. Identification of novel substrates of MAP Kinase cascades using bioengineered kinases that uniquely utilize analogs of ATP to phosphorylate substrates. Methods Mol Biol. 2010; 661:167-83. PMID: 20811983.
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    19. Li Q, Al-Ayoubi A, Guo T, Zheng H, Sarkar A, Nguyen T, Eblen ST, Grant S, Kellogg GE, Zhang S. Structure-activity relationship (SAR) studies of 3-(2-amino-ethyl)-5-(4-ethoxy-benzylidene)-thiazolidine-2,4-dione: development of potential substrate-specific ERK1/2 inhibitors. Bioorg Med Chem Lett. 2009 Nov 01; 19(21):6042-6. PMID: 19796943.
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    20. Al-Ayoubi A, Tarcsafalvi A, Zheng H, Sakati W, Eblen ST. ERK activation and nuclear signaling induced by the loss of cell/matrix adhesion stimulates anchorage-independent growth of ovarian cancer cells. J Cell Biochem. 2008 Oct 15; 105(3):875-84. PMID: 18726893.
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    21. Eblen ST, Kumar NV, Weber MJ. Using genetically engineered kinases to screen for novel protein kinase substrates: phosphorylation of kinase-associated substrates. CSH Protoc. 2007 Apr 01; 2007:pdb.prot4638. PMID: 21357057.
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    22. Eblen ST, Kumar NV, Weber MJ. Using Genetically Engineered Kinases to Screen for Novel Protein Kinase Substrates: Generation of [{gamma}-32P]ATP Analog from ADP Analog. CSH Protoc. 2007 Apr 01; 2007:pdb.prot4637. PMID: 21357056.
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    23. Eblen ST, Kumar NV, Weber MJ. Using genetically engineered kinases to screen for novel protein kinase substrates: phosphorylation of substrates in cell lysates with exogenous kinase. CSH Protoc. 2007 Apr 01; 2007:pdb.prot4639. PMID: 21357058.
      View in: PubMed
    24. Eblen ST, Kumar NV, Weber MJ. Using Genetically Engineered Kinases to Screen for Novel Protein Kinase Substrates: Identification of a Mutant Kinase/ATP Analog Pair. CSH Protoc. 2007 Apr 01; 2007:pdb.prot4636. PMID: 21357055.
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    25. Park ER, Eblen ST, Catling AD. MEK1 activation by PAK: a novel mechanism. Cell Signal. 2007 Jul; 19(7):1488-96. PMID: 17314031.
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    26. Gioeli D, Black BE, Gordon V, Spencer A, Kesler CT, Eblen ST, Paschal BM, Weber MJ. Stress kinase signaling regulates androgen receptor phosphorylation, transcription, and localization. Mol Endocrinol. 2006 Mar; 20(3):503-15. PMID: 16282370.
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    27. Sharma C, Vomastek T, Tarcsafalvi A, Catling AD, Schaeffer HJ, Eblen ST, Weber MJ. MEK partner 1 (MP1): regulation of oligomerization in MAP kinase signaling. J Cell Biochem. 2005 Mar 01; 94(4):708-19. PMID: 15547943.
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    28. Kumar NV, Eblen ST, Weber MJ. Identifying specific kinase substrates through engineered kinases and ATP analogs. Methods. 2004 Apr; 32(4):389-97. PMID: 15003601.
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    29. Eblen ST, Slack-Davis JK, Tarcsafalvi A, Parsons JT, Weber MJ, Catling AD. Mitogen-activated protein kinase feedback phosphorylation regulates MEK1 complex formation and activation during cellular adhesion. Mol Cell Biol. 2004 Mar; 24(6):2308-17. PMID: 14993270.
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    30. Slack-Davis JK, Eblen ST, Zecevic M, Boerner SA, Tarcsafalvi A, Diaz HB, Marshall MS, Weber MJ, Parsons JT, Catling AD. PAK1 phosphorylation of MEK1 regulates fibronectin-stimulated MAPK activation. J Cell Biol. 2003 Jul 21; 162(2):281-91. PMID: 12876277.
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    31. Eblen ST, Kumar NV, Shah K, Henderson MJ, Watts CK, Shokat KM, Weber MJ. Identification of novel ERK2 substrates through use of an engineered kinase and ATP analogs. J Biol Chem. 2003 Apr 25; 278(17):14926-35. PMID: 12594221.
      View in: PubMed
    32. Eblen ST, Slack JK, Weber MJ, Catling AD. Rac-PAK signaling stimulates extracellular signal-regulated kinase (ERK) activation by regulating formation of MEK1-ERK complexes. Mol Cell Biol. 2002 Sep; 22(17):6023-33. PMID: 12167697.
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    33. Eblen ST, Fautsch MP, Burnette RJ, Snyder M, Leof EB. Dissociation of p34cdc2 complex formation from phosphorylation and histone H1 kinase activity. Cancer Res. 1995 May 01; 55(9):1994-2000. PMID: 7728771.
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    34. Eblen ST, Fautsch MP, Burnette RJ, Joshi P, Leof EB. Cell cycle-dependent inhibition of p34cdc2 synthesis by transforming growth factor beta 1 in cycling epithelial cells. Cell Growth Differ. 1994 Feb; 5(2):109-16. PMID: 8180123.
      View in: PubMed
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