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Department of Infectious Diseases

Dennis Kyle

Dennis Kyle

PhD
Professor
Department of Cellular Biology
Email: .(JavaScript must be enabled to view this email address)


Educational Background

BA (1979) Biology, University of Tennessee at Chattanooga

PhD (1984) Zoology, Clemson University


Research Interests

Drug Discovery and Lead Optimization of Antiparasitic Drugs

Mechanisms of Antimalarial Drug Resistance

Drug Discovery for Pathogenic Free-living Amoebae

Natural Products Drug Discovery

Antileishmanial drug discovery


Selected Publications

  • Duvalsaint M, and Kyle DE. Phytohormones, isoprenoids and role of apicoplast in recovery from dihydroartemisinin-induced dormancy in Plasmodium falciparum. Antimicrobial Agents Chemother. 2018. Jan 8. doi: 10.1128/AAC.01771-17 [Epub ahead of print] PMID: 29311075.
  • Thomas SAL, von Salm JL, Clark S, Ferlita S, Neman P, Azhari A, Rice CA, Wilson NG, Kyle DE, and Baker BA. Keikipukalides, furanocembrane diterpenes from the Antarctic deep sea octocoral Plumarella delicatissima. J Nat Prod 2017 Dec 20. doi: 10.1021/acs.jnatprod.7b00732. [Epub ahead of print] PMID: 29260557.
  • Neelarpu R, Maignan JR, Lichorowic CL, Monastyrskyi A, Mutka TS, LaCrie AN, Blake LD, Casandra D, Mashkouri S, Burrows JN, Willis PA, Kyle DE, and Manetsch R. Design and synthesis of orally bioavailable piperazine substituted 4(1H)-quinolones with potent antimalarial activity: Structure-activity and structure-property relationship studies. J Med Chem 2017 Dec 7. doi: 10.1021/acs.jmedchem.7b00738. [Epub ahead of print] PMID: 29215279
  • Siegel SV, Rivero AV, Oberstaller J, Colon BL, de Buron I, and Kyle DE. Blood flukes Cardicola parvus and C. laruei (Trematoda: Aporocotylidae): life cycles and cryptic infection in spotted seatrout, Cynoscion nebulosus (Telost: Sciaenidae). Parasitol Int 2017 67:150-158. doi: 10.1016/j.parint.2017.10.012. PMID: 29100926
  • McQueen A, Blake LD, Azhari A, Kemp MT, McGaha TW Jr, Namelikonda N, Larsen RW, Manetsch R, Kyle DE. Synthesis, characterization, and cellular localization of a fluorescent probe of the antimalarial 8-aminoquinoline primaquine. Bioorg Med Chem Lett 2017 27:4597-4600. doi: 10.1016/j.bmcl.2017.09.030. PMID: 28939120
  • Blake LD, Johnson ME, Siegel SV, McQueen A, Iyamu ID, Shaikh AK, Shulktis MW, Manetsch R, Kyle DE. Menoctone resistance in malaria parasites is conferred by M133I mutations in cytochrome b that are transmissible through mosquitos. Antimicrobial Agents Chemother. 2017 61:e00689-17.https://doi: 10.1128/AAC.00689.17 PMID: 28584157.
  • Pradhan A, Siwo G, Singh N, Martens B, Balu B, Button-Simmons K, Tan A, Zhang M, Udenze KO, Jiang RHY, Ferdig MT, Adams JH, Kyle DE. Chemogenomic Profiling of Plasmodium falciparum as a Tool to Aid Antimalarial Drug Discovery. Sci Reports 2015; 5:15930. doi: 10.1038/srep15930. PMID: 26541648
  • Shao CL, Linington RG, Balunas MJ, Centeno A, Boudreau P, Zhang C, Engene N, Spadafora C, Mutka TS, Kyle DE, Gerwick L, Wang CY, Gerwick WH. Bastimolide A, a Potent Antimalarial Polyhydroxy Macrolide from the Marine Cyanobacterium Okeania hirsuta. J Org Chem. 2015; 80(16):7849-55. doi: 10.1021/acs/joc.5b01264. PMID: 26222145.
  • Hott A, Tucker MS, Casandra D, Sparks K, Kyle DE. Fitness of Artemisinin-Resistant Plasmodium falciparum in vitro. J Antimicrob Chemother 2015; 70(10):2787-96. doi: 10.1093/jac/dkv199. PMID: 26203183.
  • Baragaña B, Hallyburton I, Lee MC, Norcross NR, Grimaldi R, Otto TD, Proto WR, Blagborough AM, Meister S, Wirjanata G, Ruecker A, Upton LM, Abraham TS, Almeida MJ, Pradhan A, Porzelle A, Martínez MS, Bolscher JM, Woodland A, Norval S, Zuccotto F, Thomas J, Simeons F, Stojanovski L, Osuna-Cabello M, Brock PM, Churcher TS, Sala KA, Zakutansky SE, Jiménez-Díaz MB, Sanz LM, Riley J, Basak R, Campbell M, Avery VM, Sauerwein RW, Dechering KJ, Noviyanti R, Campo B, Frearson JA, Angulo-Barturen I, Ferrer-Bazaga S, Gamo FJ, Wyatt PG, Leroy D, Siegl P, Delves MJ, Kyle DE, Wittlin S, Marfurt J, Price RN, Sinden RE, Winzeler EA, Charman SA, Bebrevska L, Gray DW, Campbell S, Fairlamb AH, Willis PA, Rayner JC, Fidock DA, Read KD, Gilbert IH. A Novel Multiple-Stage Antimalarial Agent that Inhibits Protein Synthesis. Nature. 2015; 522:315-20. 2037-44. doi: 10.1038/nature14451. PMID: 26085270.
  • Hott A, Casandra D, Sparks KN, Morton LC, Castanares GG, Rutter A, Kyle DE. Artemisinin-resistant Plasmodium falciparum Exhibit Altered Patterns of Development in Infected Erythrocytes. Antimicrobial Agents Chemother. 2015. 59:3156-67. doi: 10.1128/AAC.00197-15. PMID: 25779582.
  • Rice CA, Colon BL, Alp M, Goker H, Boykin DW, Kyle DE. Bis-Benzimidazole Hits against Naegleria fowleri Discovered with New High-Throughput Screens. Antimicrob Agents Chemother. 2015;59(4):2037-44. doi: 10.1128/AAC.05122-14. PMID: 25605363; PMCID: 4356813.
  • María Belén Jiménez-Díaz, Daniel Ebertb, Yandira Salinas, Anupam Pradhan, Adele M. Lehane, Marie-Eve Myrand-Lapierre, Kathleen G. O’Loughlin, David M. Shackleford, Mariana Justino de Almeidai, Angela K. Carrilloc, Julie Clark, Adelaide Dennis, Jonathon Diep, Xiaoyan Deng, Sandra Duffy, Aaron N. Endsley, Greg Fedewa, Armand Guiguemde, Maria G. Gomez-Lorenzo, Gloria Holbrook, Jeremy Horst, Charles C. Kimk, Jian Liul, Marcus C. S. Lee, Amy Matheny, Maria Santos Martínez, Gregory Miller, Ane Rodriguez-Alejandrea, Laura Sanz, Martina Sigal, Natalie Jane Spillman, Philip D. Stein, Zheng Wangl, Fangyi Zhu, David Waterson, Spencer Knapp, Anang Shelat, Vicky M. Avery, David A. Fidock, Francisco-Javier Gamo, Susan A. Charman, Jon C. Mirsalis, Hongshen Ma, Santiago Ferrer, Kiaran Kirk, Iñigo Angulo-Barturen, Dennis E. Kyle, Joseph L. DeRisi, David M. Floyd, and R. Kiplin Guy. 2014. (+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance of Plasmodium. PNAS 111: E5455-62. PMID: 25453091.
  • Cross RM, Flanigan DL, Monastyrskyi A, LaCrue AN, Saenz FE, Maignan JR, Mutka TS, White KL, Shackleford DM, Bathurst I, Fronczek FR, Wojtas L, Guida WC, Charman SA, Burrows JN, Kyle DE, Manetsch R. 2014. Orally Bioavailable 6-Chloro-7-methoxy-4(1H)-quinolones Efficacious against Multiple Stages of Plasmodium. J Med Chem. 57: 8860-8879. PMID: 2511682.
  • Monastyrskyi A, Kyle DE, Manetsch R. 2014. 4(1H)-Pyridone and 4(1H)-Quinolone Derivatives as Antimalarials with Erythrocytic, Exoerythrocytic, and Transmission Blocking Activities. Curr Top Med Chem. 14: 1693-1705.
  • Chen N, LaCrue AN, Teuscher F, Waters NC, Gatton ML, Kyle DE, Cheng Q. 2014. Fatty acid synthesis and pyruvate metabolism pathways remain active in dihydroartemisinin induced dormant ring stages of Plasmodium falciparum. Antimicrob Agents Chemother. 58: 4773-4781. PMID: 24913167.
  • Maher SP, Crouse RB, Conway AJ, Bannister EC, Achyuta AK, Clark AY, Sinatra FL, Cuiffi JD, Adams JH, Kyle DE, Saadi WM. 2014. Microphysical space of a liver sinusoid device enables simplified long-term maintenance of chimeric mouse-expanded human hepatocytes. Biomed Microdevices 16: 727-736. doi: 10.1007/s10544-014-9877-x.
  • Henrich PP, O'Brien C, Sáenz FE, Cremers S, Kyle DE, Fidock DA. 2014. Evidence for pyronaridine as a highly effective partner drug for treatment of artemisinin-resistant malaria in a rodent model. Antimicrob Agents Chemother. 58(1):183-95.
  • Sáenz FE, Lacrue AN, Cross RM, Maignan JR, Udenze KO, Manetsch R, Kyle DE. 2013. 4-(1H)-Quinolones and 1,2,3,4-Tetrahydroacridin-9(10H)-ones prevent the transmission of Plasmodium falciparum to Anopheles freeborni. Antimicrob Agents Chemotherapy. 57(12):6187-95.
  • Nilsen, A., Lacrue, A. N., White, K. L., Forquer, I. P., Cross, R. M., Marfurt, J., Mather, M. W., Delves, M. J., Shackleford, D. M., Saenz, F. E., Morrisey, J. M., Steuten, J., Mutka, T., Li, Y., Wirjanata, G., Ryan, E., Duffy, S., Kelly, J. X., Sebayang, B. F., Zeeman, A. M., Noviyanti, R., Sinden, R. E., Kocken, C. H., Price, R. N., Avery, V. M., Angulo-Barturen, I., Jimenez-Diaz, M. B., Ferrer, S., Herreros, E., Sanz, L. M., Gamo, F. J., Bathurst, I., Burrows, J. N., Siegl, P., Guy, R. K., Winter, R. W., Vaidya, A. B., Charman, S. A., Kyle, D. E., Manetsch, R., and Riscoe, M. K. 2013. Quinolone-3-diarylethers: a new class of antimalarial drug. Science Translational Medicine. 5(177):177ra37.
  • Cheng Q, Kyle DE, Gatton ML. 2012. Artemisinin resistance in Plasmodium falciparum: A process linked to dormancy? Int J Parasitol Drugs Drug Resist. 2:249-255.
  • LaCrue AN, Sáenz FE, Cross RM, Udenze KO, Monastyrskyi A, Stein S, Mutka TS, Manetsch R, Kyle DE. 2012. 4(1H)-quinolones with liver stage activity against Plasmodium berghei. Antimicrob Agents Chemother. 57:417-24.
  • Srivastava A, Sweat JM, Azizan A, Vesely B, Kyle DE. 2012. Real-time PCR to quantify Lesihmania donovani in hamsters. J Parasitol 99(1): 145-50.
  • Balunas MJ, Grosso MF, Villa FA, Engene N, McPhail KL, Tidgewell K, Pineda LM, Gerwick L, Spadafora C, Kyle DE, Gerwick WH. 2012. Coibacins A-D, Antileishmanial Marine Cyanobacterial Polyketides with Intriguing Biosynthetic Origins. Org Lett. 14(15):3878-3881.
  • Sáenz FE, Mutka T, Udenze K, Oduola AM, Kyle DE. 2012. Novel 4-aminoquinoline analogs highly active against the blood and sexual stages of Plasmodium in vivo and in vitro. Antimicrob Agents Chemother. 56(9): 4685-92.
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