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Philip H Howe, PhD
Professor of Biochemistry & Molecular Biology
College of Medicine
MUSC

Email: howep@musc.edu
 
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Philip H Howe, PhD

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Research Interest:

The focus of the research in my laboratory is on the role that the TGF and Wnt signaling pathways play in mediating tumorigenesis. I am investigating the role of these signaling pathways in regulating epithelial-mesenchymal transition (EMT) in epithelium and apoptosis in developing B-lymphocytes. My laboratory employs in vitro cellular models of EMT and B-lymphocytes, as well as colon and breast cancer cell lines. We also employ zebrafish and mouse models of tumorigenesis to confirm our studies in vivo. I have been working in the TGF and Wnt signaling fields for ~ 25 years and my laboratory has made significant contributions in elucidating the molecular mechanisms of action of these cytokines. I have maintained continuous funding for over 20 years and have a demonstrated record of successful and productive research projects in these areas.

Honors:
Hans and Helen Koebig Endowed Chair in Clinical Oncology

Positions:
Chair, Department of Biochemistry & Molecular Biology, Medical University of South Carolina

Selected Publications:

1.Nasarre P, Gemmill RM, Potiron VA, Roche J, Lu X, Barón AE, Korch C, Garrett-Mayer E, Lagana A, Howe PH, Drabkin HA. Neuropilin-2 Is upregulated in lung cancer cells during TGF-ß1-induced epithelial-mesenchymal transition. Cancer Res. .73(23):7111-21, 2013. PMCID: PMC3926507
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2.Hussey GS, Link LA, Brown AS, Howley BV, Chaudhury A, Howe PH. Establishment of a TGFß-induced post-transcriptional EMT gene signature. PLoS One. .7(12):e52624, 2012. PMCID: PMC3527574
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3.Jiang Y, He X, Howe PH. Disabled-2 (Dab2) inhibits Wnt/ß-catenin signalling by binding LRP6 and promoting its internalization through clathrin. EMBO J. .31(10):2336-49, 2012. PMCID: PMC3364753
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4.Beach JR, Hussey GS, Miller TE, Chaudhury A, Patel P, Monslow J, Zheng Q, Keri RA, Reizes O, Bresnick AR, Howe PH, Egelhoff TT. Myosin II isoform switching mediates invasiveness after TGF-ß-induced epithelial-mesenchymal transition. Proc Natl Acad Sci U S A. .108(44):17991-6, 2011. PMCID: PMC3207690
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5.Chaudhury A, Hussey GS, Howe PH. 3'-UTR-mediated post-transcriptional regulation of cancer metastasis: beginning at the end. RNA Biol. .8(4):595-9, 2011. PMCID: PMC3360070
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6.Hussey G, Chaudhury A, Howe PH. Discovery of a metastatic pathway: implications for future cancer treatment. Future Oncol. .7(6):703-5, 2011.
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7.Hussey GS, Chaudhury A, Dawson AE, Lindner DJ, Knudsen CR, Wilce MC, Merrick WC, Howe PH. Identification of an mRNP complex regulating tumorigenesis at the translational elongation step. Mol Cell. .41(4):419-31, 2011. PMCID: PMC3061437
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8.Penheiter SG, Singh RD, Repellin CE, Wilkes MC, Edens M, Howe PH, Pagano RE, Leof EB. Type II transforming growth factor-beta receptor recycling is dependent upon the clathrin adaptor protein Dab2. Mol Biol Cell. .21(22):4009-19, 2010. PMCID: PMC2982134
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9.Mayorga ME, Dong F, Sundararaman S, Huang Y, Jiang Y, Howe PH, Penn MS. Central role for disabled-2 in mesenchymal stem cardiac protein expression and functional consequences after engraftment in acute myocardial infarction. Stem Cells Dev. .20(4):681-93, 2010.
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10.Chaudhury A, Chander P, Howe PH. Heterogeneous nuclear ribonucleoproteins (hnRNPs) in cellular processes: Focus on hnRNP E1's multifunctional regulatory roles. RNA. .16(8):1449-62, 2010. PMCID: PMC2905745
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11.Chaudhury A, Hussey GS, Ray PS, Jin G, Fox PL, Howe PH. TGF-beta-mediated phosphorylation of hnRNP E1 induces EMT via transcript-selective translational induction of Dab2 and ILEI. Nat Cell Biol. .12(3):286-93, 2010. PMCID: PMC2830561
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12.Chaudhury A, Howe PH. The tale of transforming growth factor-beta (TGFbeta) signaling: a soigné enigma. IUBMB Life. .61(10):929-39, 2009. PMCID: PMC2810629
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13.Jiang Y, Luo W, Howe PH. Dab2 stabilizes Axin and attenuates Wnt/beta-catenin signaling by preventing protein phosphatase 1 (PP1)-Axin interactions. Oncogene. .28(33):2999-3007, 2009. PMCID: PMC2804437
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14.Wildey GM, Howe PH. Runx1 is a co-activator with FOXO3 to mediate transforming growth factor beta (TGFbeta)-induced Bim transcription in hepatic cells. J Biol Chem. .284(30):20227-39, 2009. PMCID: PMC2740449
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15.Ramesh S, Wildey GM, Howe PH. Transforming growth factor beta (TGFbeta)-induced apoptosis: the rise & fall of Bim. Cell Cycle. .8(1):11-7, 2009. PMCID: PMC3191464
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16.Ramesh S, Qi XJ, Wildey GM, Robinson J, Molkentin J, Letterio J, Howe PH. TGF beta-mediated BIM expression and apoptosis are regulated through SMAD3-dependent expression of the MAPK phosphatase MKP2. EMBO Rep. .9(10):990-7, 2008. PMCID: PMC2572119
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17.Jiang Y, Prunier C, Howe PH. The inhibitory effects of Disabled-2 (Dab2) on Wnt signaling are mediated through Axin. Oncogene. .27(13):1865-75, 2007. PMCID: PMC2810718
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18.Chandrasekharan UM, Siemionow M, Unsal M, Yang L, Poptic E, Bohn J, Ozer K, Zhou Z, Howe PH, Penn M, DiCorleto PE. Tumor necrosis factor alpha (TNF-alpha) receptor-II is required for TNF-alpha-induced leukocyte-endothelial interaction in vivo. Blood. .109(5):1938-44, 2006. PMCID: PMC1801063
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19.Qi XJ, Wildey GM, Howe PH. Evidence that Ser87 of BimEL is phosphorylated by Akt and regulates BimEL apoptotic function. J Biol Chem. .281(2):813-23, 2005.
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20.Hocevar BA, Prunier C, Howe PH. Disabled-2 (Dab2) mediates transforming growth factor beta (TGFbeta)-stimulated fibronectin synthesis through TGFbeta-activated kinase 1 and activation of the JNK pathway. J Biol Chem. .280(27):25920-7, 2005.
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21.Prunier C, Howe PH. Disabled-2 (Dab2) is required for transforming growth factor beta-induced epithelial to mesenchymal transition (EMT). J Biol Chem. .280(17):17540-8, 2005.
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22.Prunier C, Hocevar BA, Howe PH. Wnt signaling: physiology and pathology. Growth Factors. .22(3):141-50, 2004.
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23.Hocevar BA, Mou F, Rennolds JL, Morris SM, Cooper JA, Howe PH. Regulation of the Wnt signaling pathway by disabled-2 (Dab2). EMBO J. .22(12):3084-94, 2003. PMCID: PMC162138
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24.Prunier C, Pessah M, Ferrand N, Seo SR, Howe P, Atfi A. The oncoprotein Ski acts as an antagonist of transforming growth factor-beta signaling by suppressing Smad2 phosphorylation. J Biol Chem. .278(28):26249-57, 2003.
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25.Wildey GM, Patil S, Howe PH. Smad3 potentiates transforming growth factor beta (TGFbeta )-induced apoptosis and expression of the BH3-only protein Bim in WEHI 231 B lymphocytes. J Biol Chem. .278(20):18069-77, 2003.
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26.Hocevar BA, Smine A, Xu XX, Howe PH. The adaptor molecule Disabled-2 links the transforming growth factor beta receptors to the Smad pathway. EMBO J. .20(11):2789-801, 2001. PMCID: PMC125498
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27.Patil S, Wildey GM, Brown TL, Choy L, Derynck R, Howe PH. Smad7 is induced by CD40 and protects WEHI 231 B-lymphocytes from transforming growth factor-beta -induced growth inhibition and apoptosis. J Biol Chem. .275(49):38363-70, 2000.
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28.Hocevar BA, Howe PH. Regulation of AP-1 activity by TGF-beta. Methods Mol Biol. .142:97-108, 2000.
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29.Hocevar BA, Howe PH. Analysis of TGF-beta-mediated synthesis of extracellular matrix components. Methods Mol Biol. .142:55-65, 2000.
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30.Brown TL, Patil S, Cianci CD, Morrow JS, Howe PH. Transforming growth factor beta induces caspase 3-independent cleavage of alphaII-spectrin (alpha-fodrin) coincident with apoptosis. J Biol Chem. .274(33):23256-62, 1999.
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31.Jin G, Howe PH. Transforming growth factor beta regulates clusterin gene expression via modulation of transcription factor c-Fos. Eur J Biochem. .263(2):534-42, 1999.
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32.Hocevar BA, Brown TL, Howe PH. TGF-beta induces fibronectin synthesis through a c-Jun N-terminal kinase-dependent, Smad4-independent pathway. EMBO J. .18(5):1345-56, 1999. PMCID: PMC1171224
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33.Brown TL, Patil S, Basnett RK, Howe PH. Caspase inhibitor BD-fmk distinguishes transforming growth factor beta-induced apoptosis from growth inhibition. Cell Growth Differ. .9(10):869-75, 1998.
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34.Brown TL, Howe PH. MADD is highly homologous to a Rab3 guanine-nucleotide exchange protein (Rab3-GEP) Curr Biol. .8(6):R191, 1998.
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35.Hocevar BA, Howe PH. Mechanisms of TGF-beta-induced cell cycle arrest. Miner Electrolyte Metab. .24(2-3):131-5, 1998.
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36.Jin G, Howe PH. Regulation of clusterin gene expression by transforming growth factor beta. J Biol Chem. .272(42):26620-6, 1997.
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37.Lee YJ, Han Y, Lu HT, Nguyen V, Qin H, Howe PH, Hocevar BA, Boss JM, Ransohoff RM, Benveniste EN. TGF-beta suppresses IFN-gamma induction of class II MHC gene expression by inhibiting class II transactivator messenger RNA expression. J Immunol. .158(5):2065-75, 1997.
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38.Hocevar BA, Howe PH. Isolation and characterization of mutant cell lines defective in transforming growth factor beta signaling. Proc Natl Acad Sci U S A. .93(15):7655-60, 1996. PMCID: PMC38802
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39.Mal A, Poon RY, Howe PH, Toyoshima H, Hunter T, Harter ML. Inactivation of p27Kip1 by the viral E1A oncoprotein in TGFbeta-treated cells. Nature. .380(6571):262-5, 1996.
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40.Reddy KB, Karode MC, Harmony AK, Howe PH. Interaction of transforming growth factor beta receptors with apolipoprotein J/clusterin. Biochemistry. .35(1):309-14, 1996.
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41.Reddy KB, Hocevar BA, Howe PH. Inhibition of G1 phase cyclin dependent kinases by transforming growth factor beta 1. J Cell Biochem. .56(3):418-25, 1994.
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42.Howe PH, Dobrowolski SF, Reddy KB, Stacey DW. Release from G1 growth arrest by transforming growth factor beta 1 requires cellular ras activity. J Biol Chem. .268(28):21448-52, 1993.
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43.Reddy KB, Howe PH. Transforming growth factor beta 1-mediated inhibition of smooth muscle cell proliferation is associated with a late G1 cell cycle arrest. J Cell Physiol. .156(1):48-55, 1993.
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44.Longstreet M, Miller B, Howe PH. Loss of transforming growth factor beta 1 (TGF-beta 1)-induced growth arrest and p34cdc2 regulation in ras-transfected epithelial cells. Oncogene. .7(8):1549-56, 1992.
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45.Howe PH, Draetta G, Leof EB. Transforming growth factor beta 1 inhibition of p34cdc2 phosphorylation and histone H1 kinase activity is associated with G1/S-phase growth arrest. Mol Cell Biol. .11(3):1185-94, 1991. PMCID: PMC369389
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46.Howe PH, Cunningham MR, Leof EB. Inhibition of mink lung epithelial cell proliferation by transforming growth factor-beta is coupled through a pertussis-toxin-sensitive substrate. Biochem J. .266(2):537-43, 1990. PMCID: PMC1131165
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47.Howe PH, Cunningham MR, Leof EB. Distinct pathways regulate transforming growth factor beta 1-stimulated proto-oncogene and extracellular matrix gene expression. J Cell Physiol. .142(1):39-45, 1990.
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48.Howe PH, Bascom CC, Cunningham MR, Leof EB. Regulation of transforming growth factor beta 1 action by multiple transducing pathways: evidence for both G protein-dependent and -independent signaling. Cancer Res. .49(21):6024-31, 1989.
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49.Akhtar RA, Honkanen RE, Howe PH, Abdel-Latif AA. M2 muscarinic receptor subtype is associated with inositol trisphosphate accumulation, myosin light chain phosphorylation and contraction in sphincter smooth muscle of rabbit iris. J Pharmacol Exp Ther. .243(2):624-32, 1987.
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50.Howe PH, Akhtar RA, Naderi S, Abdel-Latif AA. Correlative studies on the effect of carbachol on myo-inositol trisphosphate accumulation, myosin light chain phosphorylation and contraction in sphincter smooth muscle of rabbit iris. J Pharmacol Exp Ther. .239(2):574-83, 1986.
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