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Shivendra Singh, PhD
Professor and UPMC Chair in Cancer Prevention Research
2.32a Hillman Cancer Center
5117 Centre Avenue, Pittsburgh, Pa 15232
MSc (Biochemistry), Banaras Hindu University, India, 1979. PhD (Biochemistry), Banaras Hindu University, India, 1984. Postdoctoral Fellow, University of Texas Medical Branch at Galveston, 1984-1988.
Cancer chemoprevention is a relatively new but rapidly emerging sub-discipline in oncology and signifies the use of natural or synthetic agents to reverse or delay the process of carcinogenesis. Long latency of most epithelial cancers presents a large window of opportunity for intervention to prevent or slow disease progression. The research interests of the Singh laboratory include molecular characterization of novel cancer chemopreventive agents and rational design of mechanism-driven combination chemoprevention regimens. Cellular and transgenic animal models are used to screen potential cancer chemopreventive constituents from dietary and medicinal plants. Cutting edge cellular, molecular biological, Omics (metabolomics and proteomics), structural biology, and imaging techniques (MRI and bioluminescence) are used to (a) determine the mechanism of action of promising cancer chemopreventive agents, (b) monitor effects on cancer progression, and <div style="FLOAT: left; TEXT-ALIGN: center; WIDTH: 50%"><a href="http://www.pharmacology.us/FacultyPics/635073236528506318singhResearchImage.jpg" target="_blank"><img style="HEIGHT: 400px" src="http://www.pharmacology.us/FacultyPics/635073236528506318singhResearchImage.jpg">
(c) identify biomarkers predictive of tissue exposure and possibly response. Some of the agents under active investigation in the Singh laboratory include: cruciferous vegetable-derived isothiocyanates, garlic-derived organosulides, and medicinal plant constituent withaferin A. As an example, recent published work from the Singh laboratory indicates suppression of glycolysis in mammary cancer prevention by withaferin A in a transgenic mouse model (JNCI, In Press, 2013). Likewise, complementary cellular and molecular biological, targeted proteomics, and molecular modeling techniques were used to identify beta-tubulin as a novel target of cancer cell growth arrest by withaferin A (WA).
Hahm ER, J Lee, SH Kim, A Sehrawat, JA Arlotti, SS Shiva, R Bhargava and
. Metabolic alterations in mammary cancer prevention by withaferin A in a clinically-relevant mouse model. J Natl Cancer Inst, in press, 2013.
, SH Kim, A Sehrawat, JA Arlotti, ER Hahm, K Sakao, JH Beumer, RC Jankowitz, K Chandra-Kuntal, J Lee, AA Powolny and R Dhir. Biomarkers of phenethyl isothiocyanate-mediated mammary cancer chemoprevention in a clinically relevant mouse model. J Natl Cancer Inst 104:1228-1239, 2012.
Powolny AA, A Bommareddy, ER Hahm, DP Normolle, JH Beumer, JB Nelson and
. Chemopreventative potential of the cruciferous vegetable constituent phenethyl isothiocyanate in a mouse model of prostate cancer. J Natl Cancer Ins 103:571-584, 2011.
Xiao D and
. p66shc is indispensable for phenethyl isothiocyanate-induced apoptosis in human prostate cancer cells. Cancer Res 70:3150-3158, 2010.
Bommareddy A, ER Hahm, D Xiao, AA Powolny, AL Fisher, Y Jiang and
. Atg5 regulates phenethyl isothiocyanate-induced autophagic and apoptotic cell death in human prostate cancer cells. Cancer Res 69:3704-3712, 2009.
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