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Krishne Gowda
Title Assistant Professor
Institution College of Medicine
Department Pharmacology
Address 500 University Drive Hershey PA 17033
Mailbox: CH74
Telephone 7175310003
Email
Background
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.
Publications
1. 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.
  View in: PubMed
 
2. 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.
  View in: PubMed
 
3. 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.
  View in: PubMed
 
4. 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.
  View in: PubMed
 
5. 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
 
6. 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
 
7. 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.
  View in: PubMed
 
8. 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.
  View in: PubMed
 
9. 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 5; 284(23):15750-61.
  View in: PubMed
 
10. 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 1; 110(9):3426-35.
  View in: PubMed
 
11. 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 1; 177(9):6344-52.
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12. 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.
  View in: PubMed
 
13. 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.
  View in: PubMed
 
14. 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.
  View in: PubMed
 
15. 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 4; 280(9):8606-16.
  View in: PubMed
 
16. 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 4; 280(9):8617-27.
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17. 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.
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18. 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.
  View in: PubMed
 
19. 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.
  View in: PubMed
 
20. 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.
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Co-Authors  
Amin, Shantu
Gowda, Channe
Gowda, Prakasha
Sharma, Arun
Spratt, Thomas
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