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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 Dr. Howe's laboratory is on the role that the TGF and Wnt signaling pathways play in mediating tumorigenesis. He is investigating the role of these signaling pathways in regulating epithelial-mesenchymal transition (EMT) in epithelium and apoptosis in developing B-lymphocytes. His laboratory employs in vitro cellular models of EMT and B-lymphocytes, as well as colon and breast cancer cell lines. He also employs zebrafish and mouse models of tumorigenesis to confirm his studies in vivo.

Honors:
Hans and Helen Koebig Endowed Chair in Oncology

Positions:
Chair, Department of Biochemistry & Molecular Biology, Medical University of South Carolina
Interim Leader, Cancer Genes & Molecular Regulation Program, Hollings Cancer Center, Medical University of South Carolina

Selected Publications:

1.Brown AS, Mohanty BK, Howe PH. Computational Identification of Post Translational Modification Regulated RNA Binding Protein Motifs. PLoS One. .10(9):e0137696, 2015. PMID: 26368004 PMCID: PMC4569568
View in: PubMed

2.Hussey GS, Howley BV, Howe PH. Post-transcriptional mapping reveals critical regulators of metastasis. Oncoscience. .2(10):831-2, 2015. PMID: 26682267 PMCID: PMC4671942
View in: PubMed

3.Howley BV, Hussey GS, Link LA, Howe PH. Translational regulation of inhibin ßA by TGFß via the RNA-binding protein hnRNP E1 enhances the invasiveness of epithelial-to-mesenchymal transitioned cells. Oncogene. ., 2015. PMID: 26096938
View in: PubMed

4.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. PMID: 24121493 PMCID: PMC3926507
View in: PubMed

5.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. PMID: 23285117 PMCID: PMC3527574
View in: PubMed

6.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. PMID: 22491013 PMCID: PMC3364753
View in: PubMed

7.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. PMID: 22025714 PMCID: PMC3207690
View in: PubMed

8.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. PMID: 21654215 PMCID: PMC3360070
View in: PubMed

9.Hussey G, Chaudhury A, Howe PH. Discovery of a metastatic pathway: implications for future cancer treatment. Future Oncol. .7(6):703-5, 2011. PMID: 21675832
View in: PubMed

10.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. PMID: 21329880 PMCID: PMC3061437
View in: PubMed

11.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. PMID: 20881059 PMCID: PMC2982134
View in: PubMed

12.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. PMID: 20666606
View in: PubMed

13.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. PMID: 20584894 PMCID: PMC2905745
View in: PubMed

14.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. PMID: 20154680 PMCID: PMC2830561
View in: PubMed

15.Chaudhury A, Howe PH. The tale of transforming growth factor-beta (TGFbeta) signaling: a soigné enigma. IUBMB Life. .61(10):929-39, 2009. PMID: 19787707 PMCID: PMC2810629
View in: PubMed

16.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. PMID: 19581931 PMCID: PMC2804437
View in: PubMed

17.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. PMID: 19494111 PMCID: PMC2740449
View in: PubMed

18.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. PMID: 19106608 PMCID: PMC3191464
View in: PubMed

19.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. PMID: 18704116 PMCID: PMC2572119
View in: PubMed

20.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. PMID: 17922036 PMCID: PMC2810718
View in: PubMed

21.Rula ME, Cai KQ, Moore R, Yang DH, Staub CM, Capo-Chichi CD, Jablonski SA, Howe PH, Smith ER, Xu XX. Cell autonomous sorting and surface positioning in the formation of primitive endoderm in embryoid bodies. Genesis. .45(6):327-38, 2007. PMID: 17506089
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22.Bandyopadhyay S, Ashraf MZ, Daher P, Howe PH, DiCorleto PE. HOXA9 participates in the transcriptional activation of E-selectin in endothelial cells. Mol Cell Biol. .27(12):4207-16, 2007. PMID: 17452460 PMCID: PMC1900059
View in: PubMed

23.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. PMID: 17068152 PMCID: PMC1801063
View in: PubMed

24.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. PMID: 16282323
View in: PubMed

25.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. PMID: 15894542
View in: PubMed

26.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. PMID: 15734730
View in: PubMed

27.Prunier C, Hocevar BA, Howe PH. Wnt signaling: physiology and pathology. Growth Factors. .22(3):141-50, 2004. PMID: 15518237
View in: PubMed

28.Chandrasekharan UM, Yang L, Walters A, Howe P, DiCorleto PE. Role of CL-100, a dual specificity phosphatase, in thrombin-induced endothelial cell activation. J Biol Chem. .279(45):46678-85, 2004. PMID: 15339908
View in: PubMed

29.Bayon Y, Ortiz MA, Lopez-Hernandez FJ, Howe PH, Piedrafita FJ. The retinoid antagonist MX781 induces clusterin expression in prostate cancer cells via heat shock factor-1 and activator protein-1 transcription factors. Cancer Res. .64(16):5905-12, 2004. PMID: 15313936
View in: PubMed

30.Lu T, Burdelya LG, Swiatkowski SM, Boiko AD, Howe PH, Stark GR, Gudkov AV. Secreted transforming growth factor beta2 activates NF-kappaB, blocks apoptosis, and is essential for the survival of some tumor cells. Proc Natl Acad Sci U S A. .101(18):7112-7, 2004. PMID: 15118089 PMCID: PMC406474
View in: PubMed

31.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. PMID: 12805222 PMCID: PMC162138
View in: PubMed

32.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. PMID: 12732634
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33.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. PMID: 12637528
View in: PubMed

34.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. PMID: 11387212 PMCID: PMC125498
View in: PubMed

35.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. PMID: 10995749
View in: PubMed

36.Hocevar BA, Howe PH. Analysis of TGF-beta-mediated synthesis of extracellular matrix components. Methods Mol Biol. .142:55-65, 2000. PMID: 10806613
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37.Hocevar BA, Howe PH. Regulation of AP-1 activity by TGF-beta. Methods Mol Biol. .142:97-108, 2000. PMID: 10806616
View in: PubMed

38.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. PMID: 10438500
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39.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. PMID: 10406964
View in: PubMed

40.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. PMID: 10064600 PMCID: PMC1171224
View in: PubMed

41.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. PMID: 9790498
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42.Brown TL, Howe PH. MADD is highly homologous to a Rab3 guanine-nucleotide exchange protein (Rab3-GEP) Curr Biol. .8(6):R191, 1998. PMID: 9512424
View in: PubMed

43.Hocevar BA, Howe PH. Mechanisms of TGF-beta-induced cell cycle arrest. Miner Electrolyte Metab. .24(2-3):131-5, 1998. PMID: 9525695
View in: PubMed

44.Jin G, Howe PH. Regulation of clusterin gene expression by transforming growth factor beta. J Biol Chem. .272(42):26620-6, 1997. PMID: 9334243
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45.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. PMID: 9036950
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46.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. PMID: 8755531 PMCID: PMC38802
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47.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. PMID: 8637577
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48.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. PMID: 8555189
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49.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. PMID: 7876335
View in: PubMed

50.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. PMID: 8407989
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51.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. PMID: 8391008
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52.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. PMID: 1630817
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53.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. PMID: 1996085 PMCID: PMC369389
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54.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. PMID: 2156499 PMCID: PMC1131165
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55.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. PMID: 2153688
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56.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. PMID: 2507140
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57.Howe PH, Abdel-Latif AA. Purification and characterization of protein kinase C from rabbit iris smooth muscle. Myosin light-chain phosphorylation in vitro and in intact muscle. Biochem J. .255(2):423-9, 1988. PMID: 3202827 PMCID: PMC1135245
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58.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. PMID: 3500300
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59.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. PMID: 3021957
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