Now showing items 1-15 of 15

    • A broad analysis of resistance development in the malaria parasite 

      Corey, Victoria C.; Lukens, Amanda K.; Istvan, Eva S.; Lee, Marcus C. S.; Franco, Virginia; Magistrado, Pamela; Coburn-Flynn, Olivia; Sakata-Kato, Tomoyo; Fuchs, Olivia; Gnädig, Nina F.; Goldgof, Greg; Linares, Maria; Gomez-Lorenzo, Maria G.; De Cózar, Cristina; Lafuente-Monasterio, Maria Jose; Prats, Sara; Meister, Stephan; Tanaseichuk, Olga; Wree, Melanie; Zhou, Yingyao; Willis, Paul A.; Gamo, Francisco-Javier; Goldberg, Daniel E.; Fidock, David A.; Wirth, Dyann F.; Winzeler, Elizabeth A. (Nature Publishing Group, 2016)
      Microbial resistance to chemotherapy has caused countless deaths where malaria is endemic. Chemotherapy may fail either due to pre-existing resistance or evolution of drug-resistant parasites. Here we use a diverse set of ...
    • Changes in drug sensitivity and anti-malarial drug resistance mutations over time among Plasmodium falciparum parasites in Senegal 

      Van Tyne, Daria; Dieye, Baba; Valim, Clarissa; Daniels, Rachel F; Sène, Papa Diogoye; Lukens, Amanda K; Ndiaye, Mouhamadou; Bei, Amy K; Ndiaye, Yaye Die; Hamilton, Elizabeth J; Ndir, Omar; Mboup, Souleymane; Volkman, Sarah K; Wirth, Dyann F; Ndiaye, Daouda (BioMed Central, 2013)
      Background: Malaria treatment efforts are hindered by the rapid emergence and spread of drug resistant parasites. Simple assays to monitor parasite drug response in direct patient samples (ex vivo) can detect drug resistance ...
    • Diversity-Oriented Synthesis Probe Targets Plasmodium falciparum Cytochrome b Ubiquinone Reduction Site and Synergizes With Oxidation Site Inhibitors 

      Lukens, Amanda K.; Heidebrecht, Richard W.; Mulrooney, Carol; Beaudoin, Jennifer A.; Comer, Eamon; Duvall, Jeremy R.; Fitzgerald, Mark E.; Masi, Daniela; Galinsky, Kevin; Scherer, Christina A.; Palmer, Michelle; Munoz, Benito; Foley, Michael; Schreiber, Stuart L.; Wiegand, Roger C.; Wirth, Dyann F. (Oxford University Press, 2014)
      Background. The emergence and spread of drug resistance to current antimalarial therapies remains a pressing concern, escalating the need for compounds that demonstrate novel modes of action. Diversity-Oriented Synthesis ...
    • Diversity-Oriented Synthesis Yields a Novel Lead for the Treatment of Malaria 

      Mulrooney, Carol; Austin, Christopher P.; Beaudoin, Jennifer A.; Cheng, Ken Chih-Chien; Comer, Eamon; Dandapani, Sivaraman; Dick, Justin; Duvall, Jeremy R.; Ekland, Eric H.; Fidock, David A.; Guha, Rajarshi; Hinkson, Paul; Kramer, Martin; Masi, Daniela; Marcaurelle, Lisa A.; Su, Xin-Zhuan; Weïwer, Michel; Xia, Menghang; Yuan, Jing; Zhao, Jinghua; Palmer, Michelle; Munoz, Benito; Heidebrecht, Richard W; Barker, Robert Howard; Fitzgerald, Mark E.; Foley, Michael Raymond; Lukens, Amanda Kathleen; Thomas, Craig J.; Wiegand, Roger C.; Wirth, Dyann Fergus; Schreiber, Stuart L. (AmericanChemical Society, 2011)
      Here, we describe the discovery of a novel antimalarial agent using phenotypic screening of Plasmodium falciparum asexual blood-stage parasites. Screening a novel compound collection created using diversity-oriented synthesis ...
    • Diversity-Oriented Synthesis-Facilitated Medicinal Chemistry: Toward the Development of Novel Antimalarial Agents 

      Comer, Eamon; Beaudoin, Jennifer A.; Kato, Nobutaka; Fitzgerald, Mark E.; Heidebrecht, Richard W.; Lee, Maurice duPont; Masi, Daniela; Mercier, Marion; Mulrooney, Carol; Muncipinto, Giovanni; Rowley, Ann; Crespo-Llado, Keila; Serrano, Adelfa E.; Lukens, Amanda K.; Wiegand, Roger C.; Wirth, Dyann F.; Palmer, Michelle A.; Foley, Michael A.; Munoz, Benito; Scherer, Christina A.; Duvall, Jeremy R.; Schreiber, Stuart L. (American Chemical Society, 2014)
      Here, we describe medicinal chemistry that was accelerated by a diversity-oriented synthesis (DOS) pathway, and in vivo studies of our previously reported macrocyclic antimalarial agent that derived from the synthetic ...
    • Genetic Surveillance Detects Both Clonal and Epidemic Transmission of Malaria following Enhanced Intervention in Senegal 

      Daniels, Rachel Fath; Chang, Hsiao-Han; Séne, Papa Diogoye; Park, Danny C.; Neafsey, Daniel Edward; Schaffner, Stephen; Hamilton, Elizabeth Julia; Lukens, Amanda Kathleen; Van Tyne, Daria Natalie; Mboup, Souleymane; Sabeti, Pardis Christine; Ndiaye, Daouda; Wirth, Dyann Fergus; Hartl, Daniel L.; Cooke, Sarah Volkman (Public Library of Science, 2013)
      Using parasite genotyping tools, we screened patients with mild uncomplicated malaria seeking treatment at a clinic in Thiès, Senegal, from 2006 to 2011. We identified a growing frequency of infections caused by genetically ...
    • Genome-Wide SNP Genotyping Highlights the Role of Natural Selection in Plasmodium Falciparum Population Divergence 

      Wirth, Dyann F.; Sabeti, Pardis C.; Lander, Eric S.; Birren, Bruce W.; Hartl, Daniel; Wiegand, Roger; Chitnis, Chetan E.; Dash, Aditya P.; do Lago Moraes, Sandra; Ferreira, Marcelo U.; Mboup, Soulyemane; Ndir, Omar; Ndiaye, Daouda; Ousmane, Sarr; Stange-Thomann, Nicole; Gates, Casey; Tyndall, Erin; Cortese, Joseph F.; Houde, Nathan; Daniels, Rachel; Rosen, David; Lukens, Amanda; Milner, Danny; Montgomery, Philip; Park, Daniel; Volkman, Sarah K.; Schaffner, Stephen F.; Neafsey, Daniel (BioMed Central, 2008)
      Background: The malaria parasite Plasmodium falciparum exhibits abundant genetic diversity, and this diversity is key to its success as a pathogen. Previous efforts to study genetic diversity in P. falciparum have begun ...
    • Harnessing evolutionary fitness in Plasmodium falciparum for drug discovery and suppressing resistance 

      Lukens, Amanda Kathleen; Ross, L. S.; Heidebrecht, Richard W; Javier Gamo, F.; Lafuente-Monasterio, M. J.; Booker, M. L.; Hartl, Daniel L.; Wiegand, R. C.; Wirth, Dyann F. (Proceedings of the National Academy of Sciences, 2013)
      Drug resistance emerges in an ecological context where fitness costs restrict the diversity of escape pathways. These pathways are targets for drug discovery, and here we demonstrate that we can identify small-molecule ...
    • Human Cerebral Malaria and Plasmodium falciparum Genotypes in Malawi 

      Milner, Danny Arnold; Vareta, Jimmy; Valim, Clarissa; Montgomery, Jacqui; Daniels, Rachel Fath; Cooke, Sarah Volkman; Neafsey, Daniel Edward; Park, Daniel John; Schaffner, Stephen; Mahesh, Nira C; Barnes, Kayla G; Rosen, David M; Lukens, Amanda Kathleen; Van-Tyne, Daria; Wiegand, Roger C.; Sabeti, Pardis Christine; Seydel, Karl B; Glover, Simon J; Kamiza, Steve; Molyneux, Malcolm E; Taylor, Terrie E; Wirth, Dyann Fergus (BioMed Central, 2012)
      Background: Cerebral malaria, a severe form of Plasmodium falciparum infection, is an important cause of mortality in sub-Saharan African children. A Taqman 24 Single Nucleotide Polymorphisms (SNP) molecular barcode assay ...
    • Identification and Functional Validation of the Novel Antimalarial Resistance Locus PF10_0355 in Plasmodium falciparum 

      Van Tyne, Daria Natalie; Park, Daniel John; Schaffner, Stephen; Neafsey, Daniel Edward; Angelino, Elaine Lee; Cortese, Joseph F.; Barnes, Kayla G.; Rosen, David M.; Lukens, Amanda Kathleen; Daniels, Rachel Fath; Milner, Danny Arnold; Johnson, Charles A.; Shlyakhter, Ilya; Grossman, Sharon Rachel; Becker, Justin S.; Yamins, Daniel Louis Kanef; Karlsson, Elinor Kathryn; Ndiaye, Daouda; Sarr, Ousmane; Mboup, Souleymane; Happi, Christian Tientcha; Furlotte, Nicholas A.; Eskin, Eleazar; Kang, Hyun Min; Hartl, Daniel L.; Birren, Bruce W.; Wiegand, Roger C.; Lander, Eric Steven; Wirth, Dyann Fergus; Cooke, Sarah Volkman; Sabeti, Pardis Christine (Public Library of Science, 2011)
      The Plasmodium falciparum parasite's ability to adapt to environmental pressures, such as the human immune system and antimalarial drugs, makes malaria an enduring burden to public health. Understanding the genetic basis ...
    • New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections 

      McPhillie, Martin; Zhou, Ying; El Bissati, Kamal; Dubey, Jitender; Lorenzi, Hernan; Capper, Michael; Lukens, Amanda K; Hickman, Mark; Muench, Stephen; Verma, Shiv Kumar; Weber, Christopher R.; Wheeler, Kelsey; Gordon, James; Sanders, Justin; Moulton, Hong; Wang, Kai; Kim, Taek-Kyun; He, Yuqing; Santos, Tatiana; Woods, Stuart; Lee, Patty; Donkin, David; Kim, Eric; Fraczek, Laura; Lykins, Joseph; Esaa, Farida; Alibana-Clouser, Fatima; Dovgin, Sarah; Weiss, Louis; Brasseur, Gael; Wirth, Dyann; Kent, Michael; Hood, Leroy; Meunieur, Brigitte; Roberts, Craig W.; Hasnain, S. Samar; Antonyuk, Svetlana V.; Fishwick, Colin; McLeod, Rima (Nature Publishing Group, 2016)
      Toxoplasma gondii, the most common parasitic infection of human brain and eye, persists across lifetimes, can progressively damage sight, and is currently incurable. New, curative medicines are needed urgently. Herein, we ...
    • Plasmodium falciparum Cyclic Amine Resistance Locus (PfCARL), a Resistance Mechanism for Two Distinct Compound Classes 

      Magistrado, Pamela A.; Corey, Victoria C.; Lukens, Amanda K.; LaMonte, Greg; Sasaki, Erika; Meister, Stephan; Wree, Melanie; Winzeler, Elizabeth; Wirth, Dyann F. (American Chemical Society, 2016)
      MMV007564 is a novel antimalarial benzimidazolyl piperidine chemotype identified in cellular screens. To identify the genetic determinant of MMV007564 resistance, parasites were cultured in the presence of the compound to ...
    • Sequence-Based Association and Selection Scans Identify Drug Resistance Loci in the Plasmodium Falciparum Malaria Parasite 

      Park, Daniel John; Lukens, Amanda Kathleen; Neafsey, Daniel Edward; Schaffner, Stephen; Chang, Hsiao-Han; Valim, Clarissa; Ribacke, Ulf Erik; Van Tyne, Daria Natalie; Galinsky, Kevin Joseph; Galligan, Meghan; Becker, Justin S.; Ndiaye, Daouda; Mboup, Souleymane; Wiegand, Roger C.; Hartl, Daniel L.; Sabeti, Pardis Christine; Wirth, Dyann F.; Cooke, Sarah K. (Proceedings of the National Academy of Sciences, 2012)
      Through rapid genetic adaptation and natural selection, the Plasmodium falciparum parasite—the deadliest of those that cause malaria—is able to develop resistance to antimalarial drugs, thwarting present efforts to control ...
    • SNP Genotyping Identifies New Signatures of Selection in a Deep Sample of West African Plasmodium falciparum Malaria Parasites 

      Amambua-Ngwa, Alfred; Barnes, Kayla G.; Sene, Papa; Conway, David J.; Park, Daniel John; Volkman, Sarah; Bei, Amy Kristine; Lukens, Amanda Kathleen; Van Tyne, Daria Natalie; Ndiaye, Daouda; Wirth, Dyann Fergus; Neafsey, Daniel Edward; Schaffner, Stephen (Oxford University Press, 2012)
      We used a high-density single-nucleotide polymorphism array to genotype 75 Plasmodium falciparum isolates recently collected from Senegal and The Gambia to search for signals of selection in this malaria endemic region. ...
    • Triaminopyrimidine is a fast-killing and long-acting antimalarial clinical candidate 

      Hameed P., Shahul; Solapure, Suresh; Patil, Vikas; Henrich, Philipp P.; Magistrado, Pamela A.; Bharath, Sowmya; Murugan, Kannan; Viswanath, Pavithra; Puttur, Jayashree; Srivastava, Abhishek; Bellale, Eknath; Panduga, Vijender; Shanbag, Gajanan; Awasthy, Disha; Landge, Sudhir; Morayya, Sapna; Koushik, Krishna; Saralaya, Ramanatha; Raichurkar, Anandkumar; Rautela, Nikhil; Roy Choudhury, Nilanjana; Ambady, Anisha; Nandishaiah, Radha; Reddy, Jitendar; Prabhakar, K. R.; Menasinakai, Sreenivasaiah; Rudrapatna, Suresh; Chatterji, Monalisa; Jiménez-Díaz, María Belén; Martínez, María Santos; Sanz, Laura María; Coburn-Flynn, Olivia; Fidock, David A.; Lukens, Amanda K.; Wirth, Dyann F.; Bandodkar, Balachandra; Mukherjee, Kakoli; McLaughlin, Robert E.; Waterson, David; Rosenbrier-Ribeiro, Lyn; Hickling, Kevin; Balasubramanian, V.; Warner, Peter; Hosagrahara, Vinayak; Dudley, Adam; Iyer, Pravin S.; Narayanan, Shridhar; Kavanagh, Stefan; Sambandamurthy, Vasan K. (Nature Pub. Group, 2015)
      The widespread emergence of Plasmodium falciparum (Pf) strains resistant to frontline agents has fuelled the search for fast-acting agents with novel mechanism of action. Here, we report the discovery and optimization of ...