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Patrick M Woster, PhD
Professor of Drug Discovery & Biomedical Sciences
College of Pharmacy
MUSC

Email: woster@musc.edu
 
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Patrick M Woster, PhD

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Research Interest:

My laboratory is particularly interested in the design, synthesis, and evaluation of antitumor agents that produce epigenetic effects through inhibition of histone deacetylases and specific histone demethylases typified by lysine specific demethylase 1 (LSD1). This project grew out of our long-standing interest in the design and development of a variety of analogues with potent activity against a variety of cancer cell lines. I serve as Director for the MUSC Drug Design & Synthesis Core (DDSC), which combines synthetic chemistry and powerful computational resources to support high-throughput screening and pre-clinical experimental therapeutics, thus facilitating an iterative interdisciplinary framework for drug discovery. The DDSC is equipped to provide a full range of discovery chemistry services including synthetic method development, hit-to-lead structure optimization, scale-up synthesis, virtual screening, virtual docking, fragment-based drug discovery and QSAR.

Honors:
Endowed Chair in Medicinal Chemistry, SmartState Center of Economic Excellence

Positions:
Director, Drug Design & Synthesis Core, Medical University of South Carolina

Selected Publications:

1.Chaturvedi R, de Sablet T, Asim M, Piazuelo MB, Barry DP, Verriere TG, Sierra JC, Hardbower DM, Delgado AG, Schneider BG, Israel DA, Romero-Gallo J, Nagy TA, Morgan DR, Murray-Stewart T, Bravo LE, Peek RM, Fox JG, Woster PM, Casero RA, Correa P, Wilson KT. Increased Helicobacter pylori-associated gastric cancer risk in the Andean region of Colombia is mediated by spermine oxidase. Oncogene. ., 2014.
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2.Pachaiyappan B, Woster PM. Design of small molecule epigenetic modulators. Bioorg Med Chem Lett. .24(1):21-32, 2013. PMCID: PMC3879946
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3.Kumarasinghe IR, Woster PM. Synthesis and evaluation of novel cyclic Peptide inhibitors of lysine-specific demethylase 1. ACS Med Chem Lett. .5(1):29-33, 2013. PMCID: PMC4027766
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4.Yedidi RS, Liu Z, Kovari IA, Woster PM, Kovari LC. P1 and P1' para-fluoro phenyl groups show enhanced binding and favorable predicted pharmacological properties: structure-based virtual screening of extended lopinavir analogs against multi-drug resistant HIV-1 protease. J Mol Graph Model. .47:18-24, 2013.
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5.Dewdney TG, Wang Y, Liu Z, Sharma SK, Reiter SJ, Brunzelle JS, Kovari IA, Woster PM, Kovari LC. Ligand modifications to reduce the relative resistance of multi-drug resistant HIV-1 protease. Bioorg Med Chem. .21(23):7430-4, 2013.
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6.Murray-Stewart T, Hanigan CL, Woster PM, Marton LJ, Casero RA. Histone deacetylase inhibition overcomes drug resistance through a miRNA-dependent mechanism. Mol Cancer Ther. .12(10):2088-99, 2013. PMCID: PMC3808125
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7.Hayes CS, DeFeo-Mattox K, Woster PM, Gilmour SK. Elevated ornithine decarboxylase activity promotes skin tumorigenesis by stimulating the recruitment of bulge stem cells but not via toxic polyamine catabolic metabolites. Amino Acids. .46(3):543-52, 2013.
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8.Murray-Stewart T, Woster PM, Casero RA. The re-expression of the epigenetically silenced e-cadherin gene by a polyamine analogue lysine-specific demethylase-1 (LSD1) inhibitor in human acute myeloid leukemia cell lines. Amino Acids. .46(3):585-94, 2013. PMCID: PMC3692581
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9.Nowotarski SL, Woster PM, Casero RA. Polyamines and cancer: implications for chemotherapy and chemoprevention. Expert Rev Mol Med. .15:e3, 2013. PMCID: PMC4027058
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10.Jin L, Hanigan CL, Wu Y, Wang W, Park BH, Woster PM, Casero RA. Loss of LSD1 (lysine-specific demethylase 1) suppresses growth and alters gene expression of human colon cancer cells in a p53- and DNMT1(DNA methyltransferase 1)-independent manner. Biochem J. .449(2):459-68, 2013. PMCID: PMC3525012
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11.Hazeldine S, Pachaiyappan B, Steinbergs N, Nowotarski S, Hanson AS, Casero RA, Woster PM. Low molecular weight amidoximes that act as potent inhibitors of lysine-specific demethylase 1. J Med Chem. .55(17):7378-91, 2012. PMCID: PMC3482425
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12.Yedidi RS, Liu Z, Wang Y, Brunzelle JS, Kovari IA, Woster PM, Kovari LC, Gupta D. Crystal structures of multidrug-resistant HIV-1 protease in complex with two potent anti-malarial compounds. Biochem Biophys Res Commun. .421(3):413-7, 2012. PMCID: PMC3351498
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13.Schenk T, Chen WC, Göllner S, Howell L, Jin L, Hebestreit K, Klein HU, Popescu AC, Burnett A, Mills K, Casero RA, Marton L, Woster P, Minden MD, Dugas M, Wang JC, Dick JE, Müller-Tidow C, Petrie K, Zelent A. Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia. Nat Med. .18(4):605-11, 2012. PMCID: PMC3539284
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14.Sharma SK, Hazeldine S, Crowley ML, Hanson A, Beattie R, Varghese S, Senanayake TM, Hirata A, Hirata F, Huang Y, Wu Y, Steinbergs N, Murray-Stewart T, Bytheway I, Casero RA, Woster PM. Polyamine-based small molecule epigenetic modulators. Medchemcomm. .3(1):14-21, 2011. PMCID: PMC3535317
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15.Hanfrey CC, Pearson BM, Hazeldine S, Lee J, Gaskin DJ, Woster PM, Phillips MA, Michael AJ. Alternative spermidine biosynthetic route is critical for growth of Campylobacter jejuni and is the dominant polyamine pathway in human gut microbiota. J Biol Chem. .286(50):43301-12, 2011. PMCID: PMC3234850
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16.Verlinden BK, Niemand J, Snyman J, Sharma SK, Beattie RJ, Woster PM, Birkholtz LM. Discovery of novel alkylated (bis)urea and (bis)thiourea polyamine analogues with potent antimalarial activities. J Med Chem. .54(19):6624-33, 2011. PMCID: PMC3191323
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17.Goodwin AC, Destefano Shields CE, Wu S, Huso DL, Wu X, Murray-Stewart TR, Hacker-Prietz A, Rabizadeh S, Woster PM, Sears CL, Casero RA. Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis. Proc Natl Acad Sci U S A. .108(37):15354-9, 2011. PMCID: PMC3174648
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18.Fraser AV, Goodwin AC, Hacker-Prietz A, Sugar E, Woster PM, Casero RA. Knockdown of ornithine decarboxylase antizyme 1 causes loss of uptake regulation leading to increased N1, N11-bis(ethyl)norspermine (BENSpm) accumulation and toxicity in NCI H157 lung cancer cells. Amino Acids. .42(2-3):529-38, 2011. PMCID: PMC3240712
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19.Zhu Q, Huang Y, Marton LJ, Woster PM, Davidson NE, Casero RA. Polyamine analogs modulate gene expression by inhibiting lysine-specific demethylase 1 (LSD1) and altering chromatin structure in human breast cancer cells. Amino Acids. .42(2-3):887-98, 2011. PMCID: PMC3240695
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20.Woster PM. Use of polyamine derivatives as selective histone deacetylase inhibitors. Methods Mol Biol. .720:475-91, 2011. PMCID: PMC3925779
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21.Cervelli M, Bellavia G, Fratini E, Amendola R, Polticelli F, Barba M, Federico R, Signore F, Gucciardo G, Grillo R, Woster PM, Casero RA, Mariottini P. Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm. BMC Cancer. .10:555, 2010. PMCID: PMC3027604
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22.Sharma SK, Wu Y, Steinbergs N, Crowley ML, Hanson AS, Casero RA, Woster PM. (Bis)urea and (bis)thiourea inhibitors of lysine-specific demethylase 1 as epigenetic modulators. J Med Chem. .53(14):5197-212, 2010. PMCID: PMC2920492
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23.Gupta D, Yedidi RS, Varghese S, Kovari LC, Woster PM. Mechanism-based inhibitors of the aspartyl protease plasmepsin II as potential antimalarial agents. J Med Chem. .53(10):4234-47, 2010.
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24.Lee SB, Park JH, Woster PM, Casero RA, Park MH. Suppression of exogenous gene expression by spermidine/spermine N1-acetyltransferase 1 (SSAT1) cotransfection. J Biol Chem. .285(20):15548-56, 2010. PMCID: PMC2865325
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25.Huang Y, Stewart TM, Wu Y, Baylin SB, Marton LJ, Perkins B, Jones RJ, Woster PM, Casero RA. Novel oligoamine analogues inhibit lysine-specific demethylase 1 and induce reexpression of epigenetically silenced genes. Clin Cancer Res. .15(23):7217-28, 2009. PMCID: PMC2927136
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26.Senanayake MD, Amunugama H, Boncher TD, Casero RA, Woster PM. Design of polyamine-based therapeutic agents: new targets and new directions. Essays Biochem. .46:77-94, 2009. PMCID: PMC3564240
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27.Huang Y, Marton LJ, Woster PM, Casero RA. Polyamine analogues targeting epigenetic gene regulation. Essays Biochem. .46:95-110, 2009. PMCID: PMC3564236
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28.Basu HS, Thompson TA, Church DR, Clower CC, Mehraein-Ghomi F, Amlong CA, Martin CT, Woster PM, Lindstrom MJ, Wilding G. A small molecule polyamine oxidase inhibitor blocks androgen-induced oxidative stress and delays prostate cancer progression in the transgenic adenocarcinoma of the mouse prostate model. Cancer Res. .69(19):7689-95, 2009. PMCID: PMC2756327
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29.Pledgie-Tracy A, Billam M, Hacker A, Sobolewski MD, Woster PM, Zhang Z, Casero RA, Davidson NE. The role of the polyamine catabolic enzymes SSAT and SMO in the synergistic effects of standard chemotherapeutic agents with a polyamine analogue in human breast cancer cell lines. Cancer Chemother Pharmacol. .65(6):1067-81, 2009. PMCID: PMC2840063
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30.Casero RA, Woster PM. Recent advances in the development of polyamine analogues as antitumor agents. J Med Chem. .52(15):4551-73, 2009. PMCID: PMC2762202
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31.Susick L, Senanayake T, Veluthakal R, Woster PM, Kowluru A. A novel histone deacetylase inhibitor prevents IL-1beta induced metabolic dysfunction in pancreatic beta-cells. J Cell Mol Med. .13(8B):1877-85, 2009. PMCID: PMC3852426
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32.Uimari A, Keinänen TA, Karppinen A, Woster P, Uimari P, Jänne J, Alhonen L. Spermine analogue-regulated expression of spermidine/spermine N1-acetyltransferase and its effects on depletion of intracellular polyamine pools in mouse fetal fibroblasts. Biochem J. .422(1):101-9, 2009. PMCID: PMC4180119
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33.Bacchi CJ, Yarlett N, Faciane E, Bi X, Rattendi D, Weiss LM, Woster PM. Metabolism of an alkyl polyamine analog by a polyamine oxidase from the microsporidian Encephalitozoon cuniculi. Antimicrob Agents Chemother. .53(6):2599-604, 2009. PMCID: PMC2687184
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34.Wei G, DeFeo K, Hayes CS, Woster PM, Mandik-Nayak L, Gilmour SK. Elevated ornithine decarboxylase levels activate ataxia telangiectasia mutated-DNA damage signaling in normal keratinocytes. Cancer Res. .68(7):2214-22, 2008. PMCID: PMC2392890
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35.Varghese S, Senanayake T, Murray-Stewart T, Doering K, Fraser A, Casero RA, Woster PM. Polyaminohydroxamic acids and polyaminobenzamides as isoform selective histone deacetylase inhibitors. J Med Chem. .51(8):2447-56, 2008. PMCID: PMC3556737
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36.Huang Y, Greene E, Murray Stewart T, Goodwin AC, Baylin SB, Woster PM, Casero RA. Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes. Proc Natl Acad Sci U S A. .104(19):8023-8, 2007. PMCID: PMC1857229
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37.Boncher T, Bi X, Varghese S, Casero RA, Woster PM. Polyamine-based analogues as biochemical probes and potential therapeutics. Biochem Soc Trans. .35(Pt 2):356-63, 2007.
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38.Bi X, Lopez C, Bacchi CJ, Rattendi D, Woster PM. Novel alkylpolyaminoguanidines and alkylpolyaminobiguanides with potent antitrypanosomal activity. Bioorg Med Chem Lett. .16(12):3229-32, 2006.
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39.Varghese S, Gupta D, Baran T, Jiemjit A, Gore SD, Casero RA, Woster PM. Alkyl-substituted polyaminohydroxamic acids: a novel class of targeted histone deacetylase inhibitors. J Med Chem. .48(20):6350-65, 2005. PMCID: PMC3554812
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40.Pledgie A, Huang Y, Hacker A, Zhang Z, Woster PM, Davidson NE, Casero RA. Spermine oxidase SMO(PAOh1), Not N1-acetylpolyamine oxidase PAO, is the primary source of cytotoxic H2O2 in polyamine analogue-treated human breast cancer cell lines. J Biol Chem. .280(48):39843-51, 2005.
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41.Huang Y, Pledgie A, Rubin E, Marton LJ, Woster PM, Sukumar S, Casero RA, Davidson NE. Role of p53/p21(Waf1/Cip1) in the regulation of polyamine analogue-induced growth inhibition and cell death in human breast cancer cells. Cancer Biol Ther. .4(9):1006-13, 2005. PMCID: PMC3639297
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42.Devereux W, Wang Y, Stewart TM, Hacker A, Smith R, Frydman B, Valasinas AL, Reddy VK, Marton LJ, Ward TD, Woster PM, Casero RA. Induction of the PAOh1/SMO polyamine oxidase by polyamine analogues in human lung carcinoma cells. Cancer Chemother Pharmacol. .52(5):383-90, 2003.
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