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Krishne Gowda

TitleAssistant Professor
InstitutionCollege of Medicine
DepartmentPharmacology
Address500 University Drive Hershey PA 17033
Mailbox: CH74
Phone7175310003
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    PREFERRED TITLE/ROLE:



    Assistant Professor of Pharmacology



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



    Penn State Hershey Cancer Institute



    EDUCATION:



    M.S., University of Mysore, 1987

    Ph.D., University of Mysore, 2000

    Postdoctoral Fellowship, Penn State College of Medicine, 2002



    NARRATIVE:



    Our research efforts combine synthetic organic chemistry, biochemical, and molecular biological tools in an interdisciplinary approach to designing drugs that specifically target diseased cells or infectious agents. The long-term goal of our research is the development of selective strategies for the treatment of cancer and infectious diseases. Topics of current interest include: (i) Development of selective modulators of Aryl hydrocarbon receptor (SAhRM) activity. Recently, we developed a molecule SGA360 is a selective modulator of aryl hydrocarbon receptor was shown to inhibit a set of inflammatory cytokines. Future studies are needed to test whether SGA360 would be effective in treating chronic inflammatory diseases. (ii) Development of novel therapeutic agents for cancer. Currently, we developed a novel isatin derivatives were demonstrated as efficient dual inhibitors of both tubulin polymerization and the Akt pathway and good candidates for further study. Our laboratory is also involved in the synthesis of various carcinogens like polycyclic aromatic hydrocarbons (PAHs) and their metabolites like diols and diol epoxides, and tobacco-specific N-nitrosoamines (TSNAs), wherein we prepare specific carcinogens and their metabolites for bioassays and for the exploration of DNA adducts formation. We use mechanisms of chemical carcinogenesis as a tool for developing chemopreventive strategies to reduce the morbidity and mortality from cancer.


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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Chen KM, Guttenplan JB, Sun YW, Cooper T, Shalaby NA, Kosinska W, Benitez G, Aliaga C, Zhu J, Liao J, Gowda K, Amin S, Stoner G, El-Bayoumy K. Effects of Black Raspberry on Dibenzo[a,l]Pyrene Diol Epoxide Induced DNA Adducts, Mutagenesis and Tumorigenesis in the Mouse Oral Cavity. Cancer Prev Res (Phila). 2017 Nov 20. PMID: 29158340.
      View in: PubMed
    2. Guttenplan JB, Chen KM, Sun YW, Lajara B, Shalaby NAE, Kosinska W, Benitez G, Gowda K, Amin S, Stoner G, El-Bayoumy K. Effects of Black Raspberry Extract and Berry Compounds on Repair of DNA Damage and Mutagenesis Induced by Chemical and Physical Agents in Human Oral Leukoplakia and Rat Oral Fibroblasts. Chem Res Toxicol. 2017 Dec 18; 30(12):2159-2164. PMID: 29068672.
      View in: PubMed
    3. Smith KJ, Boyer JA, Muku GE, Murray IA, Gowda K, Desai D, Amin SG, Glick AB, Perdew GH. Editor's Highlight: Ah Receptor Activation Potentiates Neutrophil Chemoattractant (C-X-C Motif) Ligand 5 Expression in Keratinocytes and Skin. Toxicol Sci. 2017 Nov 01; 160(1):83-94. PMID: 28973351.
      View in: PubMed
    4. Sun YW, Chen KM, Imamura Kawasawa Y, Salzberg AC, Cooper TK, Caruso C, Aliaga C, Zhu J, Gowda K, Amin S, El-Bayoumy K. Hypomethylated Fgf3 is a potential biomarker for early detection of oral cancer in mice treated with the tobacco carcinogen dibenzo[def,p]chrysene. PLoS One. 2017; 12(10):e0186873. PMID: 29073177.
      View in: PubMed
    5. Chen KM, Schell TD, Richie JP, Sun YW, Zhang SM, Calcagnotto A, Aliaga C, Gowda K, Amin S, El-Bayoumy K. Effects of chronic alcohol consumption on DNA damage and immune regulation induced by the environmental pollutant dibenzo[a,l]pyrene in oral tissues of mice. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2017 Oct 02; 35(4):213-222. PMID: 29106334.
      View in: PubMed
    6. Muku GE, Lahoti TS, Murray IA, Podolsky MA, Smith KJ, Hubbard TD, Kuzu G, Gowda K, Amin SG, Perdew GH. Ligand-mediated cytoplasmic retention of the Ah receptor inhibits macrophage-mediated acute inflammatory responses. Lab Invest. 2017 Dec; 97(12):1471-1487. PMID: 28892097.
      View in: PubMed
    7. Pandey MK, Gowda K, Sung SS, Abraham T, Budak-Alpdogan T, Talamo G, Dovat S, Amin S. A novel dual inhibitor of microtubule and Bruton's tyrosine kinase inhibits survival of multiple myeloma and osteoclastogenesis. Exp Hematol. 2017 Sep; 53:31-42. PMID: 28647392.
      View in: PubMed
    8. Guttenplan JB, Chen KM, Sun YW, Kosinska W, Zhou Y, Kim SA, Sung Y, Gowda K, Amin S, Stoner GD, El-Bayoumy K. Effects of Black Raspberry Extract and Protocatechuic Acid on Carcinogen-DNA Adducts and Mutagenesis, and Oxidative Stress in Rat and Human Oral Cells. Cancer Prev Res (Phila). 2016 Aug; 9(8):704-12. PMID: 27267891.
      View in: PubMed
    9. Hubbard TD, Murray IA, Bisson WH, Lahoti TS, Gowda K, Amin SG, Patterson AD, Perdew GH. Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles. Sci Rep. 2015 Aug 03; 5:12689. PMID: 26235394; PMCID: PMC4522678.
    10. Song C, Gowda C, Pan X, Ding Y, Tong Y, Tan BH, Wang H, Muthusami S, Ge Z, Sachdev M, Amin SG, Desai D, Gowda K, Gowda R, Robertson GP, Schjerven H, Muschen M, Payne KJ, Dovat S. Targeting casein kinase II restores Ikaros tumor suppressor activity and demonstrates therapeutic efficacy in high-risk leukemia. Blood. 2015 Oct 08; 126(15):1813-22. PMID: 26219304; PMCID: PMC4600018.
    11. Sun YW, El-Bayoumy K, Aliaga C, Awad AS, Gowda K, Amin S, Chen KM. Tissue Distribution, Excretion and Pharmacokinetics of the Environmental Pollutant Dibenzo[def,p]chrysene in Mice. Chem Res Toxicol. 2015 Jul 20; 28(7):1427-33. PMID: 26034881; PMCID: PMC4863960.
    12. Varadarajan S, Poornima P, Milani M, Gowda K, Amin S, Wang HG, Cohen GM. Maritoclax and dinaciclib inhibit MCL-1 activity and induce apoptosis in both a MCL-1-dependent and -independent manner. Oncotarget. 2015 May 20; 6(14):12668-81. PMID: 26059440; PMCID: PMC4494965.
    13. Mohinta S, Kannan AK, Gowda K, Amin SG, Perdew GH, August A. Differential regulation of Th17 and T regulatory cell differentiation by aryl hydrocarbon receptor dependent xenobiotic response element dependent and independent pathways. Toxicol Sci. 2015 Jun; 145(2):233-43. PMID: 25716673; PMCID: PMC4471441.
    14. van den Bogaard EH, Podolsky MA, Smits JP, Cui X, John C, Gowda K, Desai D, Amin SG, Schalkwijk J, Perdew GH, Glick AB. Genetic and pharmacological analysis identifies a physiological role for the AHR in epidermal differentiation. J Invest Dermatol. 2015 May; 135(5):1320-1328. PMID: 25602157; PMCID: PMC4402116.
    15. Pogash TJ, El-Bayoumy K, Amin S, Gowda K, de Cicco RL, Barton M, Su Y, Russo IH, Himmelberger JA, Slifker M, Manni A, Russo J. Oxidized derivative of docosahexaenoic acid preferentially inhibit cell proliferation in triple negative over luminal breast cancer cells. In Vitro Cell Dev Biol Anim. 2015 Feb; 51(2):121-7. PMID: 25413005; PMCID: PMC4948656.
    16. Doi K, Liu Q, Gowda K, Barth BM, Claxton D, Amin S, Loughran TP, Wang HG. Maritoclax induces apoptosis in acute myeloid leukemia cells with elevated Mcl-1 expression. Cancer Biol Ther. 2014 Aug; 15(8):1077-86. PMID: 24842334; PMCID: PMC4119075.
    17. Fang ZZ, Krausz KW, Nagaoka K, Tanaka N, Gowda K, Amin SG, Perdew GH, Gonzalez FJ. In vivo effects of the pure aryl hydrocarbon receptor antagonist GNF-351 after oral administration are limited to the gastrointestinal tract. Br J Pharmacol. 2014 Apr; 171(7):1735-46. PMID: 24417285; PMCID: PMC3966752.
    18. Doi K, Gowda K, Liu Q, Lin JM, Sung SS, Dower C, Claxton D, Loughran TP, Amin S, Wang HG. Pyoluteorin derivatives induce Mcl-1 degradation and apoptosis in hematological cancer cells. Cancer Biol Ther. 2014; 15(12):1688-99. PMID: 25535900; PMCID: PMC4623387.
    19. Lahoti TS, Hughes JM, Kusnadi A, John K, Zhu B, Murray IA, Gowda K, Peters JM, Amin SG, Perdew GH. Aryl hydrocarbon receptor antagonism attenuates growth factor expression, proliferation, and migration in fibroblast-like synoviocytes from patients with rheumatoid arthritis. J Pharmacol Exp Ther. 2014 Feb; 348(2):236-45. PMID: 24309559; PMCID: PMC3912548.
    20. Pandey MK, Gowda K, Doi K, Sharma AK, Wang HG, Amin S. Proteasomal degradation of Mcl-1 by maritoclax induces apoptosis and enhances the efficacy of ABT-737 in melanoma cells. PLoS One. 2013; 8(11):e78570. PMID: 24223823; PMCID: PMC3817219.
    21. Narayanan GA, Murray IA, Krishnegowda G, Amin S, Perdew GH. Selective aryl hydrocarbon receptor modulator-mediated repression of CD55 expression induced by cytokine exposure. J Pharmacol Exp Ther. 2012 Aug; 342(2):345-55. PMID: 22553215; PMCID: PMC3400802.
    22. Gowda AS, Krishnegowda G, Suo Z, Amin S, Spratt TE. Low fidelity bypass of O(2)-(3-pyridyl)-4-oxobutylthymine, the most persistent bulky adduct produced by the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by model DNA polymerases. Chem Res Toxicol. 2012 Jun 18; 25(6):1195-202. PMID: 22533615.
      View in: PubMed
    23. Doi K, Li R, Sung SS, Wu H, Liu Y, Manieri W, Krishnegowda G, Awwad A, Dewey A, Liu X, Amin S, Cheng C, Qin Y, Schonbrunn E, Daughdrill G, Loughran TP, Sebti S, Wang HG. Discovery of marinopyrrole A (maritoclax) as a selective Mcl-1 antagonist that overcomes ABT-737 resistance by binding to and targeting Mcl-1 for proteasomal degradation. J Biol Chem. 2012 Mar 23; 287(13):10224-35. PMID: 22311987; PMCID: PMC3323047.
    24. 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. PMID: 22001385; PMCID: PMC3226888.
    25. 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. PMID: 21920762; PMCID: PMC3235409.
    26. Vijaya S. 4-(4-Chloro-phen-yl)-N-[(E)-4-(dimethyl-amino)-benzyl-idene]-1,3-thia-zol-2-amine. Acta Crystallogr Sect E Struct Rep Online. 2011 Aug 01; 67(Pt 8):o2115. PMID: 22091133; PMCID: PMC3213556.
    27. 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. PMID: 21524094; PMCID: PMC3118900.
    28. Zhu J, Krishnegowda G, Li G, Gowda DC. Proinflammatory responses by glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum are mainly mediated through the recognition of TLR2/TLR1. Exp Parasitol. 2011 Jul; 128(3):205-11. PMID: 21439957; PMCID: PMC3100359.
    29. 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. PMID: 20423157; PMCID: PMC2871980.
    30. Zhu J, Wu X, Goel S, Gowda NM, Kumar S, Krishnegowda G, Mishra G, Weinberg R, Li G, Gaestel M, Muta T, Gowda DC. MAPK-activated protein kinase 2 differentially regulates plasmodium falciparum glycosylphosphatidylinositol-induced production of tumor necrosis factor-{alpha} and interleukin-12 in macrophages. J Biol Chem. 2009 Jun 05; 284(23):15750-61. PMID: 19359247; PMCID: PMC2708872.
    31. Gillrie MR, Krishnegowda G, Lee K, Buret AG, Robbins SM, Looareesuwan S, Gowda DC, Ho M. Src-family kinase dependent disruption of endothelial barrier function by Plasmodium falciparum merozoite proteins. Blood. 2007 Nov 01; 110(9):3426-35. PMID: 17693580; PMCID: PMC2200906.
    32. Lu Z, Serghides L, Patel SN, Degousee N, Rubin BB, Krishnegowda G, Gowda DC, Karin M, Kain KC. Disruption of JNK2 decreases the cytokine response to Plasmodium falciparum glycosylphosphatidylinositol in vitro and confers protection in a cerebral malaria model. J Immunol. 2006 Nov 01; 177(9):6344-52. PMID: 17056565.
      View in: PubMed
    33. Naik RS, Krishnegowda G, Ockenhouse CF, Gowda DC. Naturally elicited antibodies to glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum require intact GPI structures for binding and are directed primarily against the conserved glycan moiety. Infect Immun. 2006 Feb; 74(2):1412-5. PMID: 16428795; PMCID: PMC1360366.
    34. Lim J, Gowda DC, Krishnegowda G, Luckhart S. Induction of nitric oxide synthase in Anopheles stephensi by Plasmodium falciparum: mechanism of signaling and the role of parasite glycosylphosphatidylinositols. Infect Immun. 2005 May; 73(5):2778-89. PMID: 15845481; PMCID: PMC1087374.
    35. Perraut R, Diatta B, Marrama L, Garraud O, Jambou R, Longacre S, Krishnegowda G, Dieye A, Gowda DC. Differential antibody responses to Plasmodium falciparum glycosylphosphatidylinositol anchors in patients with cerebral and mild malaria. Microbes Infect. 2005 Apr; 7(4):682-7. PMID: 15848275.
      View in: PubMed
    36. Krishnegowda G, Hajjar AM, Zhu J, Douglass EJ, Uematsu S, Akira S, Woods AS, Gowda DC. Induction of proinflammatory responses in macrophages by the glycosylphosphatidylinositols of Plasmodium falciparum: cell signaling receptors, glycosylphosphatidylinositol (GPI) structural requirement, and regulation of GPI activity. J Biol Chem. 2005 Mar 04; 280(9):8606-16. PMID: 15623512; PMCID: PMC4984258.
    37. Zhu J, Krishnegowda G, Gowda DC. Induction of proinflammatory responses in macrophages by the glycosylphosphatidylinositols of Plasmodium falciparum: the requirement of extracellular signal-regulated kinase, p38, c-Jun N-terminal kinase and NF-kappaB pathways for the expression of proinflammatory cytokines and nitric oxide. J Biol Chem. 2005 Mar 04; 280(9):8617-27. PMID: 15611045; PMCID: PMC4980998.
    38. Hegde R, Thimmaiah P, Yerigeri MC, Krishnegowda G, Thimmaiah KN, Houghton PJ. Anti-calmodulin acridone derivatives modulate vinblastine resistance in multidrug resistant (MDR) cancer cells. Eur J Med Chem. 2004 Feb; 39(2):161-77. PMID: 14987825.
      View in: PubMed
    39. Krishnegowda G, Gowda DC. Intraerythrocytic Plasmodium falciparum incorporates extraneous fatty acids to its lipids without any structural modification. Mol Biochem Parasitol. 2003 Nov; 132(1):55-8. PMID: 14563537.
      View in: PubMed
    40. Naik RS, Krishnegowda G, Gowda DC. Glucosamine inhibits inositol acylation of the glycosylphosphatidylinositol anchors in intraerythrocytic Plasmodium falciparum. J Biol Chem. 2003 Jan 17; 278(3):2036-42. PMID: 12419814.
      View in: PubMed
    41. Krishnegowda G, Thimmaiah P, Hegde R, Dass C, Houghton PJ, Thimmaiah KN. Synthesis and chemical characterization of 2-methoxy-N(10)-substituted acridones needed to reverse vinblastine resistance in multidrug resistant (MDR) cancer cells. Bioorg Med Chem. 2002 Jul; 10(7):2367-80. PMID: 11983534.
      View in: PubMed
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