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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.Conway SJ, Woster PM, Greenlee WJ, Georg G, Wang S. Epigenetics: Novel Therapeutics Targeting Epigenetics. J Med Chem. .59(4):1247-8, 2016. PMID: 26824165
View in: PubMed

2.Maganti AV, Maier B, Tersey SA, Sampley ML, Mosley AL, Özcan S, Pachaiyappan B, Woster PM, Hunter CS, Stein R, Mirmira RG. Transcriptional activity of the islet ß cell factor Pdx1 is augmented by lysine methylation catalyzed by the methyltransferase Set7/9. J Biol Chem. .290(15):9812-22, 2015. PMID: 25713082 PMCID: PMC4392279
View in: PubMed

3.Nowotarski SL, Pachaiyappan B, Holshouser SL, Kutz CJ, Li Y, Huang Y, Sharma SK, Casero RA, Woster PM. Structure-activity study for (bis)ureidopropyl- and (bis)thioureidopropyldiamine LSD1 inhibitors with 3-5-3 and 3-6-3 carbon backbone architectures. Bioorg Med Chem. .23(7):1601-12, 2015. PMID: 25725609 PMCID: PMC4396983
View in: PubMed

4.Verlinden BK, de Beer M, Pachaiyappan B, Besaans E, Andayi WA, Reader J, Niemand J, van Biljon R, Guy K, Egan T, Woster PM, Birkholtz LM. Interrogating alkyl and arylalkylpolyamino (bis)urea and (bis)thiourea isosteres as potent antimalarial chemotypes against multiple lifecycle forms of Plasmodium falciparum parasites. Bioorg Med Chem. .23(16):5131-43, 2015. PMID: 25684422 PMCID: PMC4517987
View in: PubMed

5.Conway SJ, Woster PM, Shen JK, Georg G, Wang S. Epigenetics: novel therapeutics targeting epigenetics. J Med Chem. .58(2):523-4, 2014. PMID: 25532017
View in: PubMed

6.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. .34(26):3429-40, 2014. PMID: 25174398 PMCID: PMC4345146
View in: PubMed

7.Pachaiyappan B, Woster PM. Design of small molecule epigenetic modulators. Bioorg Med Chem Lett. .24(1):21-32, 2013. PMID: 24300735 PMCID: PMC3879946
View in: PubMed

8.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. PMID: 24883177 PMCID: PMC4027766
View in: PubMed

9.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. PMID: 24291501 PMCID: PMC4520429
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10.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. PMID: 24128815
View in: PubMed

11.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. PMID: 23943804 PMCID: PMC3808125
View in: PubMed

12.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. PMID: 23884694
View in: PubMed

13.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. PMID: 23508577 PMCID: PMC3692581
View in: PubMed

14.Nowotarski SL, Woster PM, Casero RA. Polyamines and cancer: implications for chemotherapy and chemoprevention. Expert Rev Mol Med. .15:e3, 2013. PMID: 23432971 PMCID: PMC4027058
View in: PubMed

15.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. PMID: 23072722 PMCID: PMC3525012
View in: PubMed

16.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. PMID: 22876979 PMCID: PMC3482425
View in: PubMed

17.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. PMID: 22469467 PMCID: PMC3351498
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18.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. PMID: 22406747 PMCID: PMC3539284
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19.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. PMID: 23293738 PMCID: PMC3535317
View in: PubMed

20.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. PMID: 22025614 PMCID: PMC3234850
View in: PubMed

21.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. PMID: 21882831 PMCID: PMC3191323
View in: PubMed

22.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. PMID: 21876161 PMCID: PMC3174648
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23.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. PMID: 21814790 PMCID: PMC3240712
View in: PubMed

24.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. PMID: 21805138 PMCID: PMC3240695
View in: PubMed

25.Woster PM. Use of polyamine derivatives as selective histone deacetylase inhibitors. Methods Mol Biol. .720:475-91, 2011. PMID: 21318894 PMCID: PMC3925779
View in: PubMed

26.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. PMID: 20946629 PMCID: PMC3027604
View in: PubMed

27.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. PMID: 20568780 PMCID: PMC2920492
View in: PubMed

28.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. PMID: 20438064
View in: PubMed

29.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. PMID: 20212040 PMCID: PMC2865325
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30.Woster PM. Foreword: American Chemical Society Division of Medicinal Chemistry. Celebrating 100 years of excellence. J Med Chem. .52(23):7333-8, 2009. PMID: 19954244
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31.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. PMID: 19934284 PMCID: PMC2927136
View in: PubMed

32.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. PMID: 20095971 PMCID: PMC3564240
View in: PubMed

33.Huang Y, Marton LJ, Woster PM, Casero RA. Polyamine analogues targeting epigenetic gene regulation. Essays Biochem. .46:95-110, 2009. PMID: 20095972 PMCID: PMC3564236
View in: PubMed

34.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. PMID: 19773450 PMCID: PMC2756327
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35.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. PMID: 19727732 PMCID: PMC2840063
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36.Casero RA, Woster PM. Recent advances in the development of polyamine analogues as antitumor agents. J Med Chem. .52(15):4551-73, 2009. PMID: 19534534 PMCID: PMC2762202
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37.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. PMID: 20141611 PMCID: PMC3852426
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38.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. PMID: 19473115 PMCID: PMC4180119
View in: PubMed

39.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. PMID: 19223636 PMCID: PMC2687184
View in: PubMed

40.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. PMID: 18381427 PMCID: PMC2392890
View in: PubMed

41.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. PMID: 18348516 PMCID: PMC3556737
View in: PubMed

42.Wang X, Feith DJ, Welsh P, Coleman CS, Lopez C, Woster PM, O'Brien TG, Pegg AE. Studies of the mechanism by which increased spermidine/spermine N1-acetyltransferase activity increases susceptibility to skin carcinogenesis. Carcinogenesis. .28(11):2404-11, 2007. PMID: 17675337
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43.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. PMID: 17463086 PMCID: PMC1857229
View in: PubMed

44.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. PMID: 17371278
View in: PubMed

45.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. PMID: 16616495
View in: PubMed

46.Khan FD, Roychowdhury S, Nemes R, Vyas PM, Woster PM, Svensson CK. Effect of pro-inflammatory cytokines on the toxicity of the arylhydroxylamine metabolites of sulphamethoxazole and dapsone in normal human keratinocytes. Toxicology. .218(2-3):90-9, 2005. PMID: 16289751
View in: PubMed

47.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. PMID: 16190761 PMCID: PMC3554812
View in: PubMed

48.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. PMID: 16207710
View in: PubMed

49.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. PMID: 16131835 PMCID: PMC3639297
View in: PubMed

50.Vyas PM, Roychowdhury S, Woster PM, Svensson CK. Reactive oxygen species generation and its role in the differential cytotoxicity of the arylhydroxylamine metabolites of sulfamethoxazole and dapsone in normal human epidermal keratinocytes. Biochem Pharmacol. .70(2):275-86, 2005. PMID: 15894292
View in: PubMed

51.Wang Y, Hacker A, Murray-Stewart T, Frydman B, Valasinas A, Fraser AV, Woster PM, Casero RA. Properties of recombinant human N1-acetylpolyamine oxidase (hPAO): potential role in determining drug sensitivity. Cancer Chemother Pharmacol. .56(1):83-90, 2005. PMID: 15791459
View in: PubMed

52.Wang Y, Hacker A, Murray-Stewart T, Fleischer JG, Woster PM, Casero RA. Induction of human spermine oxidase SMO(PAOh1) is regulated at the levels of new mRNA synthesis, mRNA stabilization and newly synthesized protein. Biochem J. .386(Pt 3):543-7, 2005. PMID: 15496143 PMCID: PMC1134873
View in: PubMed

53.Casero RA, Frydman B, Stewart TM, Woster PM. Significance of targeting polyamine metabolism as an antineoplastic strategy: unique targets for polyamine analogues. Proc West Pharmacol Soc. .48:24-30, 2005. PMID: 16416654
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54.Goosen TC, Cillié D, Bailey DG, Yu C, He K, Hollenberg PF, Woster PM, Cohen L, Williams JA, Rheeders M, Dijkstra HP. Bergamottin contribution to the grapefruit juice-felodipine interaction and disposition in humans. Clin Pharmacol Ther. .76(6):607-17, 2004. PMID: 15592332
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55.Bacchi CJ, Rattendi D, Faciane E, Yarlett N, Weiss LM, Frydman B, Woster P, Wei B, Marton LJ, Wittner M. Polyamine metabolism in a member of the phylum Microspora (Encephalitozoon cuniculi): effects of polyamine analogues. Microbiology. .150(Pt 5):1215-24, 2004. PMID: 15133083 PMCID: PMC3109667
View in: PubMed

56.Ndjonka D, Zou Y, Bi X, Woster P, Walter RD, Lüersen K. The activator-binding site of Onchocerca volvulus S-adenosylmethionine decarboxylase, a potential drug target. Biol Chem. .384(8):1195-201, 2003. PMID: 12974388
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57.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. PMID: 12827295
View in: PubMed

58.Wang Y, Murray-Stewart T, Devereux W, Hacker A, Frydman B, Woster PM, Casero RA. Properties of purified recombinant human polyamine oxidase, PAOh1/SMO. Biochem Biophys Res Commun. .304(4):605-11, 2003. PMID: 12727196
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59.Fraser AV, Woster PM, Wallace HM. Induction of apoptosis in human leukaemic cells by IPENSpm, a novel polyamine analogue and anti-metabolite. Biochem J. .367(Pt 1):307-12, 2002. PMID: 12086584 PMCID: PMC1222862
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60.Carlisle DL, Devereux WL, Hacker A, Woster PM, Casero RA. Growth status significantly affects the response of human lung cancer cells to antitumor polyamine-analogue exposure. Clin Cancer Res. .8(8):2684-9, 2002. PMID: 12171901
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61.Lawson KR, Marek S, Linehan JA, Woster PM, Casero RA, Payne CM, Gerner EW. Detoxification of the polyamine analogue N1-ethyl-N11-[(cycloheptyl)methy]-4,8-diazaundecane (CHENSpm) by polyamine oxidase. Clin Cancer Res. .8(5):1241-7, 2002. PMID: 12006544
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