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Krishne Gowda, PhD

Krishne Gowda, PhD

Associate Professor, Department of Pharmacology
Assistant Professor, Department of Pharmacology
Scientific Program:Mechanisms of Carcinogenesis
KXG21@psu.edu
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Research Interests

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Dr. Krishne Gowda's research efforts combine synthetic organic chemistry, biochemical and molecular biological tools in an interdisciplinary approach to designing and synthesis of small molecules that specifically target diseased cells or infectious agents.

The long-term goal of the research is the development of selective strategies for the treatment of cancer and infectious diseases. Topics of current interest include:

  • Development of selective modulators of Aryl hydrocarbon receptor (SAhRM) activity. Recently, the lab developed a molecule SGA360 and analogs as selective modulators of aryl hydrocarbon receptor, which was shown to inhibit a set of inflammatory cytokines. Future studies are needed to test whether SGA360 and analogs would be useful in treating chronic inflammatory diseases.
  • Development of novel therapeutic agents for cancer. Currently, the lab has developed novel isatin derivatives that were demonstrated as aldehyde dehydrogenase (ALDH) inhibitors and suitable candidates for further study for the anticancer activity. The lab developed maritoclax and pyoluteorin derivatives as Mcl-1 inhibitors and is also involved in the synthesis of various carcinogens like polycyclic aromatic hydrocarbons and their metabolites like diols and diol epoxides and tobacco-specific N-nitrosamines, wherein they prepare specific carcinogens and their metabolites for bioassays and the exploration of DNA adducts formation. The lab uses mechanisms of chemical carcinogenesis as a tool for developing chemopreventive strategies to reduce the morbidity and mortality from cancer.
  • Neoplasms
  • Aryl Hydrocarbon Receptors
  • Plasmodium falciparum
  • Glycosylphosphatidylinositols
  • dibenzo(a,l)pyrene
  • Tobacco
  • Ligands
  • Carcinogens
  • DNA Damage
  • Apoptosis
  • Cytokines
  • Macrophages
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Recent Publications

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2023

Rikken, G, Smith, KJ, van den Brink, NJM, Smits, JPH, Gowda, K, Alnemri, A, Kuzu, GE, Murray, IA, Lin, JM, Smits, JGA, van Vlijmen-Willems, IM, Amin, SG, Perdew, GH & van den Bogaard, EH 2023, 'Lead optimization of aryl hydrocarbon receptor ligands for treatment of inflammatory skin disorders', Biochemical Pharmacology, vol. 208, 115400. https://doi.org/10.1016/j.bcp.2022.115400

2022

Chen, KM, Sun, YW, Sun, D, Gowda, K, Amin, S & El-Bayoumy, K 2022, 'Black Raspberry Extract Enhances Glutathione Conjugation of the Fjord-Region Diol Epoxide Derived from the Tobacco Carcinogen Dibenzo[ def, p]chrysene in Human Oral Cells', Chemical research in toxicology, vol. 35, no. 11, pp. 2152-2159. https://doi.org/10.1021/acs.chemrestox.2c00246
Alden, NA, Arrizabalaga, JH, Liu, Y, Amin, S, Gowda, K, Yao, S, Archetti, M, Glick, AB & Hayes, DJ 2022, 'Delivery of Therapeutic miR-148b Mimic via Poly(β Amino Ester) Polyplexes for Post-transcriptional Gene Regulation and Apoptosis of A549 Cells', Langmuir, vol. 38, no. 32, pp. 9833-9843. https://doi.org/10.1021/acs.langmuir.2c00913
Chen, KM, Sun, YW, Krebs, NM, Sun, D, Krzeminski, J, Reinhart, L, Gowda, K, Amin, S, Mallery, S, Richie, JP & El-Bayoumy, K 2022, 'Detection of DNA adducts derived from the tobacco carcinogens, benzo[a]pyrene and dibenzo[def,p]chrysene in human oral buccal cells', Carcinogenesis, vol. 43, no. 8, pp. 746-753. https://doi.org/10.1093/carcin/bgac058
Elbezanti, WO, Al-Odat, OS, Chitren, R, Singh, JK, Srivastava, SK, Gowda, K, Amin, S, Robertson, GP, Nemmara, VV, Jonnalagadda, SC, Budak-Alpdogan, T & Pandey, MK 2022, 'Development of a novel Bruton’s tyrosine kinase inhibitor that exerts anti-cancer activities potentiates response of chemotherapeutic agents in multiple myeloma stem cell-like cells', Frontiers in Pharmacology, vol. 13, 894535. https://doi.org/10.3389/fphar.2022.894535

2021

Chen, KM, Thompson, H, Vanden-Heuvel, JP, Sun, YW, Trushin, N, Aliaga, C, Gowda, K, Amin, S, Stanley, B, Manni, A & El-Bayoumy, K 2021, 'Lipoxygenase catalyzed metabolites derived from docosahexaenoic acid are promising antitumor agents against breast cancer', Scientific reports, vol. 11, no. 1, 410. https://doi.org/10.1038/s41598-020-79716-x

2020

Chen, KM, Sun, YW, Kawasawa, YI, Salzberg, AC, Zhu, J, Gowda, K, Aliaga, C, Amin, S, Atkins, H & El-Bayoumy, K 2020, 'Black raspberry inhibits oral tumors in mice treated with the tobacco smoke constituent dibenzo(def,p)chrysene via genetic and epigenetic alterations', Cancer Prevention Research, vol. 13, no. 4, pp. 357-365. https://doi.org/10.1158/1940-6207.CAPR-19-0496
Dinavahi, SS, Gowda, R, Bazewicz, CG, Battu, MB, Lin, JM, Chitren, RJ, Pandey, MK, Amin, S, Robertson, GP & Gowda, K 2020, 'Design, synthesis characterization and biological evaluation of novel multi-isoform ALDH inhibitors as potential anticancer agents', European Journal of Medicinal Chemistry, vol. 187, 111962. https://doi.org/10.1016/j.ejmech.2019.111962
Dinavahi, SS, Gowda, R, Gowda, K, Bazewicz, CG, Chirasani, VR, Battu, MB, Berg, A, Dokholyan, NV, Amin, S & Robertson, GP 2020, 'Development of a Novel Multi-Isoform ALDH Inhibitor Effective as an Antimelanoma Agent', Molecular cancer therapeutics, vol. 19, no. 2, pp. 447-459. https://doi.org/10.1158/1535-7163.MCT-19-0360
Song, C, Ge, Z, Ding, Y, Tan, BH, Desai, D, Gowda, K, Amin, S, Gowda, R, Robertson, GP, Yue, F, Huang, S, Spiegelman, V, Payne, JL, Reeves, ME, Gurel, Z, Iyer, S, Dhanyamraju, PK, Xiang, M, Kawasawa, YI, Cury, NM, Yunes, JA, McGrath, M, Schramm, J, Su, R, Yang, Y, Zhao, Z, Lyu, X, Muschen, M, Payne, KJ, Gowda, C & Dovat, S 2020, 'IKAROS and CK2 regulate expression of BCL-XL and chemosensitivity in high-risk B-cell acute lymphoblastic leukemia', Blood, vol. 136, no. 13, pp. 1520-1534. https://doi.org/10.1182/blood.2019002655
Dong, F, Hao, F, Murray, IA, Smith, PB, Koo, I, Tindall, AM, Kris-Etherton, PM, Gowda, K, Amin, SG, Patterson, AD & Perdew, GH 2020, 'Intestinal microbiota-derived tryptophan metabolites are predictive of Ah receptor activity', Gut microbes, vol. 12, no. 1, pp. 1-24. https://doi.org/10.1080/19490976.2020.1788899
Christensen, ND, Chen, KM, Hu, J, Stairs, DB, Sun, YW, Aliaga, C, Balogh, KK, Atkins, H, Shearer, D, Li, J, Brendle, SA, Gowda, K, Amin, S, Walter, V, Viscidi, R & El-Bayoumy, K 2021, 'The environmental pollutant and tobacco smoke constituent dibenzo[def,p]chrysene is a co-factor for malignant progression of mouse oral papillomavirus infections', Chemico-Biological Interactions, vol. 333, 109321. https://doi.org/10.1016/j.cbi.2020.109321
Annageldiyev, C, Gowda, K, Patel, T, Bhattacharya, P, Tan, SF, Iyer, S, Desai, D, Dovat, S, Feith, DJ, Loughran, TP, Amin, S, Claxton, D & Sharma, A 2020, 'The novel Isatin analog KS99 targets stemness markers in acute myeloid leukemia', Haematologica, vol. 105, no. 3, pp. 687-696. https://doi.org/10.3324/haematol.2018.212886

2019

Guttenplan, JB, Chen, KM, Sun, YW, Shalaby, NAE, Kosinska, W, Desai, D, Gowda, K, Amin, S & El-Bayoumy, K 2019, 'Effects of the Tobacco Carcinogens N′-Nitrosonornicotine and Dibenzo[ a, l]pyrene Individually and in Combination on DNA Damage in Human Oral Leukoplakia and on Mutagenicity and Mutation Profiles in lacI Mouse Tongue', Chemical research in toxicology, vol. 32, no. 9, pp. 1893-1899. https://doi.org/10.1021/acs.chemrestox.9b00257
Hubbard, TD, Liu, Q, Murray, IA, Dong, F, Miller, C, Smith, PB, Gowda, K, Lin, JM, Amin, S, Patterson, AD & Perdew, GH 2019, 'Microbiota Metabolism Promotes Synthesis of the Human Ah Receptor Agonist 2,8-Dihydroxyquinoline', Journal of Proteome Research, vol. 18, no. 4, pp. 1715-1724. https://doi.org/10.1021/acs.jproteome.8b00946
Muku, GE, Blazanin, N, Dong, F, Smith, PB, Thiboutot, D, Gowda, K, Amin, S, Murray, IA & Perdew, GH 2019, 'Selective Ah Receptor Ligands Mediate Enhanced SREBP1 Proteolysis to Restrict Lipogenesis in Sebocytes', Toxicological Sciences, vol. 171, no. 1, pp. 146-158. https://doi.org/10.1093/toxsci/kfz140
Muku, GE, Kusnadi, A, Kuzu, G, Tanos, R, Murray, IA, Gowda, K, Amin, S & Perdew, GH 2020, 'Selective Ah receptor modulators attenuate NPC1L1-mediated cholesterol uptake through repression of SREBP-2 transcriptional activity', Laboratory Investigation, vol. 100, no. 2, pp. 250-264. https://doi.org/10.1038/s41374-019-0306-x
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