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Arun Sharma
Title Associate Professor
Institution College of Medicine
Department Pharmacology
Address 500 University Drive Hershey PA 17033
Mailbox: CH72
Telephone 7175310003 x285016
Email
Background
PREFERRED TITLE/ROLE:

Associate Professor of Pharmacology

SECONDARY APPOINTMENT(S)/ INSTITUTE(S)/ CENTER(S):

Penn State Hershey Cancer Institute, The Huck Institutes of the Life Sciences

GRADUATE PROGRAM AFFILIATIONS:

Biomedical Sciences: Tranlational Therapeutics Option, Pharmacology, Integrative Biosciences: Molecular Toxicology

EDUCATION:

M.S., Chemistry, Organic Chemistry; North Eastern Hill University, 1991
Ph.D., Organic Synthesis; North Eastern Hill University, 1997

NARRATIVE:

The main focus of research in this lab has been to develop novel molecules for cancer therapy and prevention, and test them in vitro and in vivo on different cancer models. The strategies that we generally adapt for designing new agents include optimization of (i) naturally occurring agents, that are known for their anticancer properties, (ii) existing drugs or agents that fail in clinical trials, and (iii) lead compounds obtained from chemical library screening, to enhance potency, bioavailability and therapeutic/chemopreventive index. An example of natural product optimization includes the development of ISC-4, an organoselenium analog of isothiocyanates (ITCs) that occur naturally in cruciferous vegetables. ISC-4 was shown to be a PI3K/Akt inhibitor that effectively inhibited tumor growth in melanoma and colon cancer xenograft models without any apparent systemic toxicity. Our ongoing studies have also shown ISC-4 to be an effective in preventing against NNK induced lung tumorigenesis. Currently, a project is assessing the therapeutic efficacy of this agent as a lung cancer therapeutic agent. Our lab is intensively involved in elucidating the underlying mechanisms that could explain better anticancer efficacy of ISC-4 and other isoselenocyanate compounds as compared to ITCs. Extensive structure-activity studies exploiting these functionalities are underway. In addition, this lab has been engaged in optimization of inhibitors of sphingosine kinase, farnesyl transferase, topoisomerase, and Mek etc.

Our laboratory is also involved in structure-activity studies with mutagenic and carcinogenic polycyclic aromatic hydrocarbons (PAHs) and tobacco-specific N-nitrosoamines (TSNAs), wherein we prepare specific carcinogens and their metabolites for bioassays and for the exploration of DNA adduct formation. We use mechanisms of chemical carcinogenesis as a tool for developing chemopreventive strategies to reduce the morbidity and mortality from cancer.
Publications
1. Allen JE, Gallant JN, Dicker DT, Amin S, Irby RB, Sharma AK, El-Deiry WS. The Akt Inhibitor ISC-4 Synergizes with Cetuximab in 5-FU-Resistant Colon Cancer. PLoS One. 2013; 8(3):e59380.
  View in: PubMed
 
2. Sharma AK, Amin S. Post SELECT: selenium on trial. Future Med Chem. 2013 Feb; 5(2):163-74.
  View in: PubMed
 
3. Crampsie MA, Pandey MK, Desai D, Spallholz J, Amin S, Sharma AK. Phenylalkyl isoselenocyanates vs phenylalkyl isothiocyanates: Thiol reactivity and its implications. Chem Biol Interact. 2012 Oct 25; 200(1):28-37.
  View in: PubMed
 
4. Cheng Y, Sk UH, Zhang Y, Ren X, Zhang L, Huber-Keener KJ, Sun YW, Liao J, Amin S, Sharma AK, Yang JM. Rational incorporation of selenium into temozolomide elicits superior antitumor activity associated with both apoptotic and autophagic cell death. PLoS One. 2012; 7(4):e35104.
  View in: PubMed
 
5. Lin JM, Prakasha Gowda AS, Sharma AK, Amin S. In vitro growth inhibition of human cancer cells by novel honokiol analogs. Bioorg Med Chem. 2012 May 15; 20(10):3202-11.
  View in: PubMed
 
6. Young MM, Takahashi Y, Khan O, Park S, Hori T, Yun J, Sharma AK, Amin S, Hu CD, Zhang J, Kester M, Wang HG. Autophagosomal membrane serves as platform for intracellular death-inducing signaling complex (iDISC)-mediated caspase-8 activation and apoptosis. J Biol Chem. 2012 Apr 6; 287(15):12455-68.
  View in: PubMed
 
7. Guttenplan JB, Kosinska W, Zhao ZL, Chen KM, Aliaga C, DelTondo J, Cooper T, Sun YW, Zhang SM, Jiang K, Bruggeman R, Sharma AK, Amin S, Ahn K, El-Bayoumy K. Mutagenesis and carcinogenesis induced by dibenzo[a,l]pyrene in the mouse oral cavity: a potential new model for oral cancer. Int J Cancer. 2012 Jun 15; 130(12):2783-90.
  View in: PubMed
 
8. Crowell SR, Amin SG, Anderson KA, Krishnegowda G, Sharma AK, Soelberg JJ, Williams DE, Corley RA. Preliminary physiologically based pharmacokinetic models for benzo[a]pyrene and dibenzo[def,p]chrysene in rodents. Toxicol Appl Pharmacol. 2011 Dec 15; 257(3):365-76.
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9. Krishnegowda G, Prakasha Gowda AS, Tagaram HR, Carroll KF, Irby RB, Sharma AK, Amin S. Synthesis and biological evaluation of a novel class of isatin analogs as dual inhibitors of tubulin polymerization and Akt pathway. Bioorg Med Chem. 2011 Oct 15; 19(20):6006-14.
  View in: PubMed
 
10. Olson KC, Sun D, Chen G, Sharma AK, Amin S, Ropson IJ, Spratt TE, Lazarus P. Characterization of dibenzo[a,l]pyrene-trans-11,12-diol (dibenzo[def,p]chrysene) glucuronidation by UDP-glucuronosyltransferases. Chem Res Toxicol. 2011 Sep 19; 24(9):1549-59.
  View in: PubMed
 
11. Crampsie MA, Jones N, Das A, Aliaga C, Desai D, Lazarus P, Amin S, Sharma AK. Phenylbutyl isoselenocyanate modulates phase I and II enzymes and inhibits 4-(methylnitrosamino)-1-(3-pyridyl)- 1-butanone-induced DNA adducts in mice. Cancer Prev Res (Phila). 2011 Nov; 4(11):1884-94.
  View in: PubMed
 
12. Zhang SM, Chen KM, Aliaga C, Sun YW, Lin JM, Sharma AK, Amin S, El-Bayoumy K. Identification and quantification of DNA adducts in the oral tissues of mice treated with the environmental carcinogen dibenzo[a,l]pyrene by HPLC-MS/MS. Chem Res Toxicol. 2011 Aug 15; 24(8):1297-303.
  View in: PubMed
 
13. Sharma AK, Kline CL, Berg A, Amin S, Irby RB. The Akt inhibitor ISC-4 activates prostate apoptosis response protein-4 and reduces colon tumor growth in a nude mouse model. Clin Cancer Res. 2011 Jul 1; 17(13):4474-83.
  View in: PubMed
 
14. Sk UH, Prakasha Gowda AS, Crampsie MA, Yun JK, Spratt TE, Amin S, Sharma AK. Development of novel naphthalimide derivatives and their evaluation as potential melanoma therapeutics. Eur J Med Chem. 2011 Aug; 46(8):3331-8.
  View in: PubMed
 
15. Krishnegowda G, Sharma AK, Krzeminski J, Gowda AS, Lin JM, Desai D, Spratt TE, Amin S. Facile syntheses of O(2)-[4-(3-pyridyl-4-oxobut-1-yl]thymidine, the major adduct formed by tobacco specific nitrosamine 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) in vivo, and its site-specifically adducted oligodeoxynucleotides. Chem Res Toxicol. 2011 Jun 20; 24(6):960-7.
  View in: PubMed
 
16. Sharma AK. Sphingo-guanidines and their use as inhibitors of sphingosine kinase (WO2010078247). Expert Opin Ther Pat. 2011 May; 21(5):807-12.
  View in: PubMed
 
17. Murray IA, Flaveny CA, Chiaro CR, Sharma AK, Tanos RS, Schroeder JC, Amin SG, Bisson WH, Kolluri SK, Perdew GH. Suppression of cytokine-mediated complement factor gene expression through selective activation of the Ah receptor with 3',4'-dimethoxy-a-naphthoflavone. Mol Pharmacol. 2011 Mar; 79(3):508-19.
  View in: PubMed
 
18. Nguyen N, Sharma A, Nguyen N, Sharma AK, Desai D, Huh SJ, Amin S, Meyers C, Robertson GP. Melanoma chemoprevention in skin reconstructs and mouse xenografts using isoselenocyanate-4. Cancer Prev Res (Phila). 2011 Feb; 4(2):248-58.
  View in: PubMed
 
19. Hengst JA, Wang X, Sk UH, Sharma AK, Amin S, Yun JK. Development of a sphingosine kinase 1 specific small-molecule inhibitor. Bioorg Med Chem Lett. 2010 Dec 15; 20(24):7498-502.
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20. Sun D, Chen G, Dellinger RW, Sharma AK, Lazarus P. Characterization of 17-dihydroexemestane glucuronidation: potential role of the UGT2B17 deletion in exemestane pharmacogenetics. Pharmacogenet Genomics. 2010 Oct; 20(10):575-85.
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21. Sharma AK, Sk UH, Gimbor MA, Hengst JA, Wang X, Yun J, Amin S. Synthesis and bioactivity of sphingosine kinase inhibitors and their novel aspirinyl conjugated analogs. Eur J Med Chem. 2010 Sep; 45(9):4149-56.
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22. Palkar PS, Borland MG, Naruhn S, Ferry CH, Lee C, Sk UH, Sharma AK, Amin S, Murray IA, Anderson CR, Perdew GH, Gonzalez FJ, Müller R, Peters JM. Cellular and pharmacological selectivity of the peroxisome proliferator-activated receptor-beta/delta antagonist GSK3787. Mol Pharmacol. 2010 Sep; 78(3):419-30.
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23. Sharma AK, Sk UH, He P, Peters JM, Amin S. Synthesis of isosteric selenium analog of the PPARbeta/delta agonist GW501516 and comparison of biological activity. Bioorg Med Chem Lett. 2010 Jul 15; 20(14):4050-2.
  View in: PubMed
 
24. Murray IA, Krishnegowda G, DiNatale BC, Flaveny C, Chiaro C, Lin JM, Sharma AK, Amin S, Perdew GH. Development of a selective modulator of aryl hydrocarbon (Ah) receptor activity that exhibits anti-inflammatory properties. Chem Res Toxicol. 2010 May 17; 23(5):955-66.
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25. Wang BD, Kline CL, Pastor DM, Olson TL, Frank B, Luu T, Sharma AK, Robertson G, Weirauch MT, Patierno SR, Stuart JM, Irby RB, Lee NH. Prostate apoptosis response protein 4 sensitizes human colon cancer cells to chemotherapeutic 5-FU through mediation of an NF kappaB and microRNA network. Mol Cancer. 2010; 9:98.
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26. Sk UH, Sharma AK, Ghosh S, Bhattacharya S. Synthesis and biological evaluation of novel spiro 6-methoxytetralin-1,3'-pyrrolidine based organoselenocyanates against cadmium-induced oxidative and hepatic damage in mice. Eur J Med Chem. 2010 Aug; 45(8):3265-73.
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27. Foreman JE, Sharma AK, Amin S, Gonzalez FJ, Peters JM. Ligand activation of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) inhibits cell growth in a mouse mammary gland cancer cell line. Cancer Lett. 2010 Feb 28; 288(2):219-25.
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28. Blevins-Primeau AS, Sun D, Chen G, Sharma AK, Gallagher CJ, Amin S, Lazarus P. Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites. Cancer Res. 2009 Mar 1; 69(5):1892-900.
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29. Sharma A, Sharma AK, Madhunapantula SV, Desai D, Huh SJ, Mosca P, Amin S, Robertson GP. Targeting Akt3 signaling in malignant melanoma using isoselenocyanates. Clin Cancer Res. 2009 Mar 1; 15(5):1674-85.
  View in: PubMed
 
30. Sharma AK, Sharma A, Desai D, Madhunapantula SV, Huh SJ, Robertson GP, Amin S. Synthesis and anticancer activity comparison of phenylalkyl isoselenocyanates with corresponding naturally occurring and synthetic isothiocyanates. J Med Chem. 2008 Dec 25; 51(24):7820-6.
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31. Bedi R, Du J, Sharma AK, Gomes I, Ackerman SJ. Human C/EBP-epsilon activator and repressor isoforms differentially reprogram myeloid lineage commitment and differentiation. Blood. 2009 Jan 8; 113(2):317-27.
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32. He P, Borland MG, Zhu B, Sharma AK, Amin S, El-Bayoumy K, Gonzalez FJ, Peters JM. Effect of ligand activation of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) in human lung cancer cell lines. Toxicology. 2008 Dec 5; 254(1-2):112-7.
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33. Borland MG, Foreman JE, Girroir EE, Zolfaghari R, Sharma AK, Amin S, Gonzalez FJ, Ross AC, Peters JM. Ligand activation of peroxisome proliferator-activated receptor-beta/delta inhibits cell proliferation in human HaCaT keratinocytes. Mol Pharmacol. 2008 Nov; 74(5):1429-42.
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34. Sharma AK, Gowdahalli K, Gimbor M, Amin S. Synthesis, microsome-mediated metabolism, and identification of major metabolites of environmental pollutant naphtho[8,1,2-ghi]chrysene. Chem Res Toxicol. 2008 May; 21(5):1154-62.
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35. Girroir EE, Hollingshead HE, Billin AN, Willson TM, Robertson GP, Sharma AK, Amin S, Gonzalez FJ, Peters JM. Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands inhibit growth of UACC903 and MCF7 human cancer cell lines. Toxicology. 2008 Jan 14; 243(1-2):236-43.
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36. Sharma AK, Gowdahalli K, Krzeminski J, Amin S. Microwave-assisted Suzuki cross-coupling reaction, a key step in the synthesis of polycyclic aromatic hydrocarbons and their metabolites. J Org Chem. 2007 Nov 9; 72(23):8987-9.
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37. Hollingshead HE, Killins RL, Borland MG, Girroir EE, Billin AN, Willson TM, Sharma AK, Amin S, Gonzalez FJ, Peters JM. Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands do not potentiate growth of human cancer cell lines. Carcinogenesis. 2007 Dec; 28(12):2641-9.
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38. Sun D, Sharma AK, Dellinger RW, Blevins-Primeau AS, Balliet RM, Chen G, Boyiri T, Amin S, Lazarus P. Glucuronidation of active tamoxifen metabolites by the human UDP glucuronosyltransferases. Drug Metab Dispos. 2007 Nov; 35(11):2006-14.
  View in: PubMed
 
39. Zheng Y, Sun D, Sharma AK, Chen G, Amin S, Lazarus P. Elimination of antiestrogenic effects of active tamoxifen metabolites by glucuronidation. Drug Metab Dispos. 2007 Oct; 35(10):1942-8.
  View in: PubMed
 
40. Mahadevan B, Luch A, Atkin J, Nguyen T, Sharma AK, Amin S, Baird WM. Investigation of the genotoxicity of dibenzo[c,p]chrysene in human carcinoma MCF-7 cells in culture. Chem Biol Interact. 2006 Dec 15; 164(3):181-91.
  View in: PubMed
 
41. Sharma A, Tran MA, Liang S, Sharma AK, Amin S, Smith CD, Dong C, Robertson GP. Targeting mitogen-activated protein kinase/extracellular signal-regulated kinase kinase in the mutant (V600E) B-Raf signaling cascade effectively inhibits melanoma lung metastases. Cancer Res. 2006 Aug 15; 66(16):8200-9.
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42. Nelson G, Ross JA, Pimentel M, Desai D, Sharma AK, Amin S, Nesnow S. Characterization of naphtho[1,2-a]pyrene and naphtho[1,2-e]pyrene DNA adducts in C3H10T1/2 fibroblasts. Cancer Lett. 2007 Mar 18; 247(2):309-17.
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43. Sharma AK, Amin S. Synthesis and identification of major metabolites of environmental pollutant dibenzo[c,mno]chrysene. Chem Res Toxicol. 2005 Sep; 18(9):1438-43.
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44. Sharma AK, Lin JM, Desai D, Amin S. Convenient syntheses of dibenzo[c,p]chrysene and its possible proximate and ultimate carcinogens: in vitro metabolism and DNA adduction studies. J Org Chem. 2005 Jun 24; 70(13):4962-70.
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45. El-Bayoumy K, Sharma AK, Lin JM, Krzeminski J, Boyiri T, King LC, Lambert G, Padgett W, Nesnow S, Amin S. Identification of 5-(deoxyguanosin-N2-yl)- 1,2-dihydroxy-1,2-dihydro-6-aminochrysene as the major DNA lesion in the mammary gland of rats treated with the environmental pollutant 6-nitrochrysene. Chem Res Toxicol. 2004 Dec; 17(12):1591-9.
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46. Sun YW, Guengerich FP, Sharma AK, Boyiri T, Amin S, el-Bayoumy K. Human cytochromes P450 1A1 and 1B1 catalyze ring oxidation but not nitroreduction of environmental pollutant mononitropyrene isomers in primary cultures of human breast cells and cultured MCF-10A and MCF-7 cell lines. Chem Res Toxicol. 2004 Aug; 17(8):1077-85.
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47. Sharma AK, Kumar S, Amin S. A Highly Abbreviated Synthesis of Dibenzo[def,p]chrysene and Its 12-Methoxy Derivative, a Key Precursor for the Synthesis of the Proximate and Ultimate Carcinogens of Dibenzo[def,p]chrysene. J Org Chem. 2004 May 28; 69(11):3979-82.
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48. Mahadevan B, Parsons H, Musafia T, Sharma AK, Amin S, Pereira C, Baird WM. Effect of artificial mixtures of environmental polycyclic aromatic hydrocarbons present in coal tar, urban dust, and diesel exhaust particulates on MCF-7 cells in culture. Environ Mol Mutagen. 2004; 44(2):99-107.
  View in: PubMed
 
49. Desai D, Sharma AK, Lin JM, Krzeminski J, Pimentel M, El-Bayoumy K, Nesnow S, Amin S. Synthesis, in vitro metabolism, cell transformation, mutagenicity, and DNA adduction of dibenzo[c,mno]chrysene. Chem Res Toxicol. 2002 Jul; 15(7):964-71.
  View in: PubMed
 
50. El-Bayoumy K, Desai D, Boyiri T, Rosa J, Krzeminski J, Sharma AK, Pittman B, Amin S. Comparative tumorigenicity of the environmental pollutant 6-nitrochrysene and its metabolites in the rat mammary gland. Chem Res Toxicol. 2002 Jul; 15(7):972-8.
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Co-Authors  
Amin, Shantu
Desai, Dhimant
Krzeminski, Jacek
Lin, Jyh ming
Peters, Jeffrey
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