Patrick M. Woster

Prof. Patrick M. Woster

Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA
orcid

Research Focus & Metrics

Academic Career Length

41Years (1986-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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11 March 2012 in Nature Medicine
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Journal Article
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TSTino Schenk
Tino Schenk
WCWeihsu Claire Chen
Weihsu Claire Chen
SGStefanie Göllner
Stefanie Göllner
LHLouise Howell
Louise Howell
LJLiqing Jin
Liqing Jin
AZArthur Zelent
Arthur Zelent

29 August 2011 in Proceedings of the National Academy of Sciences
Verified
Journal Article
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AGAndrew C. Goodwin
Andrew C. Goodwin
CSChristina E. Destefano Shields
Christina E. Destefano Shields
SWShaoguang Wu
Shaoguang Wu
DHDavid L. Huso
David L. Huso
XWXinQun Wu
XinQun Wu
RJRobert A. Casero, Jr.
Robert A. Casero, Jr.
It is estimated that the etiology of 20–30% of epithelial cancers is directly associated with inflammation, although the direct molecular events linking inflammation and carcinogenesis are poorly defined. In the context of gastrointestinal disease, the bacterium enterotoxigenicBacteroides fragilis(ETBF) is a significant source of chronic inflammation and has been implicated as a risk factor for colorectal cancer. Spermine oxidase (SMO) is a polyamine catabolic enzyme that is highly inducible by inflammatory stimuli resulting in increased reactive oxygen species (ROS) and DNA damage. We now demonstrate that purifiedB. fragilistoxin (BFT) up-regulates SMO in HT29/c1 and T84 colonic epithelial cells, resulting in SMO-dependent generation of ROS and induction of γ-H2A.x, a marker of DNA damage. Further, ETBF-induced colitis in C57BL/6 mice is associated with increased SMO expression and treatment of mice with an inhibitor of polyamine catabolism,N1,N4-bis(2,3-butandienyl)-1,4-butanediamine (MDL 72527), significantly reduces ETBF-induced chronic inflammation and proliferation. Most importantly, in the multiple intestinal neoplasia (Min) mouse model, treatment with MDL 72527 reduces ETBF-induced colon tumorigenesis by 69% (P< 0.001). The results of these studies indicate that SMO is a source of bacteria-induced ROS directly associated with tumorigenesis and could serve as a unique target for chemoprevention.

15 September 1998 in Proceedings of the National Academy of Sciences
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Journal Article
Open access
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HHHyo Chol Ha
Hyo Chol Ha
NSNilantha S. Sirisoma
Nilantha S. Sirisoma
PKPeriannan Kuppusamy
Periannan Kuppusamy
JZJay L. Zweier
Jay L. Zweier
Patrick M. WosterPatrick M. Woster
Patrick M. Woster
RJRobert A. Casero, Jr.
Robert A. Casero, Jr.
The polyamines are small organic cations that are absolutely required for eukaryotic cell growth. Although their growth requirements are well established, the molecular functions of the polyamines are ill-defined. Oxidative damage to DNA by reactive oxygen species is a continual problem that cells must guard against to survive. The polyamine spermine, which is normally found in millimolar concentrations in the nucleus, is shown here to function directly as a free radical scavenger, and adducts formed as a result of this function are identified. These data suggest that spermine is a major natural intracellular compound capable of protecting DNA from free radical attack.

30 March 2007 in Amino Acids
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Journal Article
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JRJ. E. Rider
J. E. Rider
AHA. Hacker
A. Hacker
CMC. A. Mackintosh
C. A. Mackintosh
APA. E. Pegg
A. E. Pegg
Patrick M. WosterPatrick M. Woster
Patrick M. Woster
RJRobert A. Casero, Jr.
Robert A. Casero, Jr.

22 February 2013 in Expert Reviews in Molecular Medicine
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Journal Article
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SNShannon L. Nowotarski
Shannon L. Nowotarski
Patrick M. WosterPatrick M. Woster
Patrick M. Woster
RJRobert A. Casero, Jr.
Robert A. Casero, Jr.
Polyamines are small organic cations that are essential for normal cell growth and development in eukaryotes. Under normal physiological conditions, intracellular polyamine concentrations are tightly regulated through a dynamic network of biosynthetic and catabolic enzymes, and a poorly characterised transport system. This precise regulation ensures that the intracellular concentration of polyamines is maintained within strictly controlled limits. It has frequently been observed that the metabolism of, and the requirement for, polyamines in tumours is frequently dysregulated. Elevated levels of polyamines have been associated with breast, colon, lung, prostate and skin cancers, and altered levels of rate-limiting enzymes in both biosynthesis and catabolism have been observed. Based on these observations and the absolute requirement for polyamines in tumour growth, the polyamine pathway is a rational target for chemoprevention and chemotherapeutics. Here we describe the recent advances made in the polyamine field and focus on the roles of polyamines and polyamine metabolism in neoplasia through a discussion of the current animal models for the polyamine pathway, chemotherapeutic strategies that target the polyamine pathway, chemotherapeutic clinical trials for polyamine pathway-specific drugs and ongoing clinical trials targeting polyamine biosynthesis.

8 May 2007 in Proceedings of the National Academy of Sciences
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Journal Article
Closed access
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YHYi Huang
Yi Huang
EGEriko Greene
Eriko Greene
Tracy Murray StewartTracy Murray Stewart
Tracy Murray Stewart
AGAndrew C. Goodwin
Andrew C. Goodwin
SBStephen B. Baylin
Stephen B. Baylin
RJRobert A. Casero, Jr.
Robert A. Casero, Jr.
Epigenetic chromatin modification is a major regulator of eukaryotic gene expression, and aberrant epigenetic silencing of gene expression contributes to tumorigenesis. Histone modifications include acetylation, phosphorylation, and methylation, resulting in a combination of histone marks known collectively as the histone code. The chromatin marks at a given promoter determine, in part, whether specific promoters are in an open/active conformation or closed/repressed conformation. Dimethyl-lysine 4 histone H3 (H3K4me2) is a transcription-activating chromatin mark at gene promoters, and demethylation of this mark by the lysine-specific demethylase 1 (LSD1), a homologue of polyamine oxidases, may broadly repress gene expression. We now report that novel biguanide and bisguanidine polyamine analogues are potent inhibitors of LSD1. These analogues inhibit LSD1 in human colon carcinoma cells and affect a reexpression of multiple, aberrantly silenced genes important in the development of colon cancer, including members of the secreted frizzle-related proteins ( SFRPs ) and the GATA family of transcription factors. Furthermore, we demonstrate by chromatin immunoprecipitation analysis that the reexpression is concurrent with increased H3K4me2 and acetyl-H3K9 marks, decreased H3K9me1 and H3K9me2 repressive marks. We thus define important new agents for reversing aberrant repression of gene transcription.