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2. Chloroquine resistance evolution in Plasmodium falciparum is mediated by the putative amino acid transporter AAT1

Author

Amambua-Ngwa, Alfred, Button-Simons, Katrina A., Li, Xue, Kumar, Sudhir, Brenneman, Katelyn Vendrely, Ferrari, Marco, Checkley, Lisa A., Haile, Meseret T., Shoue, Douglas A., McDew-White, Marina, Tindall, Sarah M., Reyes, Ann, Delgado, Elizabeth, Dalhoff, Haley, Larbalestier, James K., Amato, Roberto, Pearson, Richard D., Taylor, Alexander B., Nosten, François H., D’Alessandro, Umberto, Kwiatkowski, Dominic, Cheeseman, Ian H., Kappe, Stefan H. I., Avery, Simon V., Conway, David J., Vaughan, Ashley M., Ferdig, Michael T., and Anderson, Timothy J. C.

Published
2023
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7. The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice

Author

Button-Simons, Katrina A., Kumar, Sudhir, Carmago, Nelly, Haile, Meseret T., Jett, Catherine, Checkley, Lisa A., Kennedy, Spencer Y., Pinapati, Richard S., Shoue, Douglas A., McDew-White, Marina, Li, Xue, Nosten, François H., Kappe, Stefan H., Anderson, Timothy J. C., Romero-Severson, Jeanne, Ferdig, Michael T., Emrich, Scott J., Vaughan, Ashley M., and Cheeseman, Ian H.

Published
2021
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8. PlasmodiumGPI‐anchored micronemal antigen is essential for parasite transmission through the mosquito host.

Author

Jennison, Charlie, Armstrong, Janna M., Dankwa, Dorender A., Hertoghs, Nina, Kumar, Sudhir, Abatiyow, Biley A., Naung, Myo, Minkah, Nana K., Swearingen, Kristian E., Moritz, Robert, Barry, Alyssa E., Kappe, Stefan H. I., and Vaughan, Ashley M.

Subjects
PLASMODIUM, CIRCUMSPOROZOITE protein, MOSQUITOES, LIFE cycles (Biology), PLASMODIUM berghei, PARASITES
Abstract

Plasmodium parasites, the eukaryotic pathogens that cause malaria, feature three distinct invasive forms tailored to the host environment they must navigate and invade for life cycle progression. One conserved feature of these invasive forms is the micronemes, apically oriented secretory organelles involved in egress, motility, adhesion, and invasion. Here we investigate the role of GPI‐anchored micronemal antigen (GAMA), which shows a micronemal localization in all zoite forms of the rodent‐infecting species Plasmodium berghei. ∆GAMA parasites are severely defective for invasion of the mosquito midgut. Once formed, oocysts develop normally, however, sporozoites are unable to egress and exhibit defective motility. Epitope‐tagging of GAMA revealed tight temporal expression late during sporogony and showed that GAMA is shed during sporozoite gliding motility in a similar manner to circumsporozoite protein. Complementation of P. berghei knockout parasites with full‐length P. falciparum GAMA partially restored infectivity to mosquitoes, indicating conservation of function across Plasmodium species. A suite of parasites with GAMA expressed under the promoters of CTRP, CAP380, and TRAP, further confirmed the involvement of GAMA in midgut infection, motility, and vertebrate infection. These data show GAMA's involvement in sporozoite motility, egress, and invasion, implicating GAMA as a regulator of microneme function. [ABSTRACT FROM AUTHOR]

Published
2024
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9. APlasmodium falciparumgenetic cross reveals the contributions ofpfcrtandplasmepsin II/IIIto piperaquine drug resistance

Author

Kane, John, primary, Li, Xue, additional, Kumar, Sudhir, additional, Button-Simons, Katrina A., additional, Vendrely Brenneman, Katelyn M., additional, Dahlhoff, Haley, additional, Sievert, Mackenzie A.C., additional, Checkley, Lisa A., additional, Shoue, Douglas A., additional, Singh, Puspendra P., additional, Abatiyow, Biley A., additional, Haile, Meseret T., additional, Nair, Shalini, additional, Reyes, Ann, additional, Tripura, Rupam, additional, Peto, Tom, additional, Lek, Dysoley, additional, Kappe, Stefan H.I., additional, Dhorda, Mehul, additional, Nkhoma, Standwell C, additional, Cheeseman, Ian H., additional, Vaughan, Ashley M., additional, Anderson, Timothy J. C., additional, and Ferdig, Michael T., additional

Published
2023
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11. Global gene expression of human malaria parasite liver stages throughout intrahepatocytic development

Author

Zanghi, Gigliola, primary, Patel, Hardik, additional, Camargo, Nelly, additional, Smith, Jenny L., additional, Bae, Yeji, additional, Flannery, Erika L., additional, Chuenchob, Vorada, additional, Fishbaugher, Matthew E., additional, Mikolajczak, Sebastian A, additional, Roobsoong, Wanlapa, additional, Sattabongkot, Jetsumon, additional, Hayes, Kiera, additional, Vaughan, Ashley M., additional, and Kappe, Stefan H. I., additional

Published
2023
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17. A genetically engineered Plasmodium falciparum parasite vaccine provides protection from controlled human malaria infection

Author

Murphy, Sean C., primary, Vaughan, Ashley M., additional, Kublin, James G., additional, Fishbauger, Matthew, additional, Seilie, Annette M., additional, Cruz, Kurtis P., additional, Mankowski, Tracie, additional, Firat, Melike, additional, Magee, Sara, additional, Betz, Will, additional, Kain, Heather, additional, Camargo, Nelly, additional, Haile, Meseret T., additional, Armstrong, Janna, additional, Fritzen, Emma, additional, Hertoghs, Nina, additional, Kumar, Sudhir, additional, Sather, D. Noah, additional, Pinder, Leeya F., additional, Deye, Gregory A., additional, Galbiati, Shirley, additional, Geber, Casey, additional, Butts, Jessica, additional, Jackson, Lisa A., additional, and Kappe, Stefan H. I., additional

Published
2022
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21. Humoral protection against mosquito bite-transmitted Plasmodium falciparum infection in humanized mice

Author

Sack, Brandon K., Mikolajczak, Sebastian A., Fishbaugher, Matthew, Vaughan, Ashley M., Flannery, Erika L., Nguyen, Thao, Betz, Will, Jane Navarro, Mary, Foquet, Lander, Steel, Ryan W. J., Billman, Zachary P., Murphy, Sean C., Hoffman, Stephen L., Chakravarty, Sumana, Sim, B. Kim Lee, Behet, Marije, Reuling, Isaie J., Walk, Jona, Scholzen, Anja, Sauerwein, Robert W., Ishizuka, Andrew S., Flynn, Barbara, Seder, Robert A., and Kappe, Stefan H. I.

Published
2017
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23. A Malaria Parasite Cross Reveals Genetic Determinants of Plasmodium falciparum Growth in Different Culture Media

Author

Kumar, Sudhir, primary, Li, Xue, additional, McDew-White, Marina, additional, Reyes, Ann, additional, Delgado, Elizabeth, additional, Sayeed, Abeer, additional, Haile, Meseret T., additional, Abatiyow, Biley A., additional, Kennedy, Spencer Y., additional, Camargo, Nelly, additional, Checkley, Lisa A., additional, Brenneman, Katelyn V., additional, Button-Simons, Katrina A., additional, Duraisingh, Manoj T., additional, Cheeseman, Ian H., additional, Kappe, Stefan H. I., additional, Nosten, François, additional, Ferdig, Michael T., additional, Vaughan, Ashley M., additional, and Anderson, Tim J. C., additional

Published
2022
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24. An amino acid transporter AAT1 plays a pivotal role in chloroquine resistance evolution in malaria parasites

Author

Amambua-Ngwa, Alfred, primary, Button-Simons, Katrina A., additional, Li, Xue, additional, Kumar, Sudhir, additional, Brenneman, Katelyn Vendrely, additional, Ferrari, Marco, additional, Checkley, Lisa A., additional, Haile, Meseret T., additional, Shoue, Douglas A., additional, McDew-White, Marina, additional, Tindall, Sarah M., additional, Reyes, Ann, additional, Delgado, Elizabeth, additional, Dalhoff, Haley, additional, Larbalestier, James K., additional, Amato, Roberto, additional, Pearson, Richard D., additional, Taylor, Alexander B., additional, Nosten, François H., additional, D’Alessandro, Umberto, additional, Kwiatkowski, Dominic, additional, Cheeseman, Ian H., additional, Kappe, Stefan H. I., additional, Avery, Simon V., additional, Conway, David J., additional, Vaughan, Ashley M., additional, Ferdig, Michael T., additional, and Anderson, Timothy J. C., additional

Published
2022
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26. Optimizing bulk segregant analysis of drug resistance using Plasmodium falciparum genetic crosses conducted in humanized mice

Author

Brenneman, Katelyn Vendrely, primary, Li, Xue, additional, Kumar, Sudhir, additional, Delgado, Elizabeth, additional, Checkley, Lisa A., additional, Shoue, Douglas A., additional, Reyes, Ann, additional, Abatiyow, Biley A., additional, Haile, Meseret T., additional, Tripura, Rupam, additional, Peto, Tom, additional, Lek, Dysoley, additional, Button-Simons, Katrina A., additional, Kappe, Stefan H.I., additional, Dhorda, Mehul, additional, Nosten, François, additional, Nkhoma, Standwell C., additional, Cheeseman, Ian H., additional, Vaughan, Ashley M., additional, Ferdig, Michael T., additional, and Anderson, Tim J.C., additional

Published
2022
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28. Plasmodium GPI-Anchored Micronemal Antigen is essential for parasite transmission through the mosquito host

Author

Jennison, Charlie, primary, Gibson, Janna M., additional, Hertoghs, Nina, additional, Dankwa, Dorender A., additional, Kumar, Sudhir, additional, Abatiyow, Biley A., additional, Naung, Myo, additional, Minkah, Nana K., additional, Swearingen, Kristian E., additional, Moritz, Robert L, additional, Barry, Alyssa. E., additional, Kappe, Stefan H. I., additional, and Vaughan, Ashley M., additional

Published
2022
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31. Plasmodium falciparum Calcium-Dependent Protein Kinase 4 is Critical for Male Gametogenesis and Transmission to the Mosquito Vector

Author

Kumar, Sudhir, primary, Haile, Meseret T., additional, Hoopmann, Michael R., additional, Tran, Linh T., additional, Michaels, Samantha A., additional, Morrone, Seamus R., additional, Ojo, Kayode K., additional, Reynolds, Laura M., additional, Kusebauch, Ulrike, additional, Vaughan, Ashley M., additional, Moritz, Robert L., additional, Kappe, Stefan H. I., additional, and Swearingen, Kristian E., additional

Published
2021
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32. Optimizing bulk segregant analysis of drug resistance using Plasmodium falciparum genetic crosses conducted in humanized mice

Author

Brenneman, Katelyn Vendrely, primary, Li, Xue, additional, Kumar, Sudhir, additional, Delgado, Elizabeth, additional, Checkley, Lisa A., additional, Shoue, Douglas A., additional, Reyes, Ann, additional, Abatiyow, Biley, additional, Haile, Meseret, additional, Tripura, Rupam, additional, Peto, Tom, additional, Lek, Dysoley, additional, Button-Simons, Katrina A., additional, Kappe, Stefan H.I., additional, Dhorda, Mehul, additional, Nosten, Francois, additional, Nkhoma, Standwell C., additional, Cheeseman, Ian H, additional, Vaughan, Ashley M, additional, Ferdig, Michael T, additional, and Anderson, Tim JC, additional

Published
2021
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35. Beyond Blood Smears: Qualification of Plasmodium 18S rRNA as a Biomarker for Controlled Human Malaria Infections

Author

Seilie, Annette M., Chang, Ming, Hanron, Amelia E., Billman, Zachary P., Stone, Brad C., Zhou, Kevin, Olsen, Tayla M., Daza, Glenda, Ortega, Jose, Cruz, Kurtis R., Smith, Nahum, Healy, Sara A., Neal, Jillian, Wallis, Carolyn K., Shelton, Lisa, Mankowski, Tracie (VonGoedert), Wong-Madden, Sharon, Mikolajczak, Sebastian A., Vaughan, Ashley M., Kappe, Stefan H. I., Fishbaugher, Matt, Betz, Will, Kennedy, Mark, Hume, Jen C. C., Talley, Angela K., Hoffman, Stephen L., Chakravarty, Sumana, Sim, B. Kim Lee, Richie, Thomas L., Wald, Anna, Plowe, Christopher V., Lyke, Kirsten E., Adams, Matthew, Fahle, Gary A., Cowan, Elliot P., Duffy, Patrick E., Kublin, James G., and Murphy, Sean C.

Subjects
Plasmodium, Reverse Transcriptase Polymerase Chain Reaction, RNA, Ribosomal, 18S, Humans, Reproducibility of Results, Articles, Real-Time Polymerase Chain Reaction, Multiplex Polymerase Chain Reaction, Biomarkers, RNA, Protozoan, Malaria
Abstract

18S rRNA is a biomarker that provides an alternative to thick blood smears in controlled human malaria infection (CHMI) trials. We reviewed data from CHMI trials at non-endemic sites that used blood smears and Plasmodium 18S rRNA/rDNA biomarker nucleic acid tests (NATs) for time to positivity. We validated a multiplex quantitative reverse transcription–polymerase chain reaction (qRT-PCR) for Plasmodium 18S rRNA, prospectively compared blood smears and qRT-PCR for three trials, and modeled treatment effects at different biomarker-defined parasite densities to assess the impact on infection detection, symptom reduction, and measured intervention efficacy. Literature review demonstrated accelerated NAT-based infection detection compared with blood smears (mean acceleration: 3.2–3.6 days). For prospectively tested trials, the validated Plasmodium 18S rRNA qRT-PCR positivity was earlier (7.6 days; 95% CI: 7.1–8.1 days) than blood smears (11.0 days; 95% CI: 10.3–11.8 days) and significantly preceded the onset of grade 2 malaria-related symptoms (12.2 days; 95% CI: 10.6–13.3 days). Discrepant analysis showed that the risk of a blood smear–positive, biomarker-negative result was negligible. Data modeling predicted that treatment triggered by specific biomarker-defined thresholds can differentiate complete, partial, and non-protective outcomes and eliminate many grade 2 and most grade 3 malaria-related symptoms post-CHMI. Plasmodium 18S rRNA is a sensitive and specific biomarker that can justifiably replace blood smears for infection detection in CHMI trials in non-endemic settings. This study led to biomarker qualification through the U.S. Food and Drug Administration for use in CHMI studies at non-endemic sites, which will facilitate biomarker use for the qualified context of use in drug and vaccine trials.

Published
2019

37. Complete Plasmodium falciparum liver-stage development in liver-chimeric mice

Author

Vaughan, Ashley M., Mikolajczak, Sebastian A., Wilson, Elizabeth M., Grompe, Markus, Kaushansky, Alexis, Camargo, Nelly, Bia1, John, Ploss, Alexander, and Kappe, Stefan H.I.

Subjects
Liver diseases -- Causes of -- Research, Plasmodium falciparum -- Health aspects -- Research, Health care industry
Abstract

Plasmodium falciparum, which causes the most lethal form of human malaria, replicates in the host liver during the initial stage of infection. However, in vivo malaria liver-stage (LS) studies in humans are virtually impossible, and in vitro models of LS development do not reconstitute relevant parasite growth conditions. To overcome these obstacles, we have adopted a robust mouse model for the study of P. falciparum LS in vivo: the immunocompromised and. fumarylacetoacetate hydrolase-deficient mouse (Fah-/-, Rag2-/-, Il2rg-/-, termed the FRG mouse) engrafted with human hepatocytes (FRG huHep). FRG huHep mice supported. vigorous, quantifiable P. falciparum LS development that culminated in complete maturation of LS at approximately 7 days after infection, providing a relevant model for LS development in humans. The infections allowed observations of previously unknown expression of proteins in LS, including P. falciparum translocon of exported proteins 150 (PTEX150) and exported protein-2 (EXP-2), components of a known parasite protein export machinery. LS schizonts exhibited exoerythrocytic merozoite formation and merosome release. Furthermore, FRG mice backcrossed to the NOD background and repopulated with huHeps and human red blood cells supported reproducible transition from LS infection to blood-stage infection. Thus, these mice constitute reliable models to study human LS directly in vivo and demonstrate utility for studies of LS to-blood-stage transition of a human malaria parasite., Introduction Plasmodium falciparum is the most deadly of the human malaria parasites. The disease continues to be a global health crisis and causes more than 250 million new clinical cases [...]

Published
2012
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41. Optimizing Bulk Segregant Analysis of Drug Resistance Using Plasmodium Falciparum Genetic Crosses Conducted in Humanized Mice

Author

Brenneman, Katelyn V., primary, Li, Xue, additional, Kumar, Sudhir, additional, Delgado, Elizabeth, additional, Checkley, Lisa A., additional, Shoue, Douglas A., additional, Reyes, Ann, additional, Abatiyow, Biley A., additional, Haile, Meseret T., additional, Tripura, Rupam, additional, Peto, Tom, additional, Lek, Dysoley, additional, Button-Simons, Katrina A., additional, Kappe, Stefan H., additional, Dhorda, Mehul, additional, Nosten, François, additional, Nkhoma, Standwell C., additional, Cheeseman, Ian, additional, Vaughan, Ashley M., additional, Ferdig, Michael T., additional, and Anderson, Timothy JC, additional

Published
2021
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46. Additional file 1 of Purification and production of Plasmodium falciparum zygotes from in vitro culture using magnetic column and Percoll density gradient

Author

Yaxian Zhou, Grieser, Alexis M., Do, Julie, Itsara, Leslie S., Vaughan, Ashley M., and Ghosh, Anil K.

Abstract

Additional file 1: Figure S1. Flow cytometry analysis on macrogametes and zygotes. Macrogamete populations were purified through MACS columns and Nycodenz gradients. Zygote populations were purified through MACS columns and Percoll gradients. 10,000 events were recorded for each sample. Control populations expressed GFP measured with a FITC-488 laser; test populations expressed both GFP and DyeCycle Orange DNA stain measured with Cy5.5 laser. The gating tree was set as follows: SSC-H vs. SSC-A (doublet exclusion); SSC-A vs. FSC-A (population of interest); GFP-A/Alexa Fluor 488-A vs. PE-Cy5-5-A (DNA content of GFP-expressing cells). a Representative histogram from one experiment displaying DNA content (PE-Cy5-5-A) through expression of Cy5.5 DNA stain, normalized to mode. Blue peak corresponds to macrogamete population, red peak corresponds to zygote population. b Chart displaying DNA content of zygote populations (darker bar) relative to macrogamete populations (lighter bar). Median PE-Cy5-5-A expression values from four separate experiments were averaged for macrogametes or zygotes and displayed as relative DNA content (n).

Published
2020
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47. Additional file 2 of Purification and production of Plasmodium falciparum zygotes from in vitro culture using magnetic column and Percoll density gradient

Author

Yaxian Zhou, Grieser, Alexis M., Do, Julie, Itsara, Leslie S., Vaughan, Ashley M., and Ghosh, Anil K.

Subjects
Computer Science::Performance, Computer Science::Networking and Internet Architecture, Quantum Physics, Physics::Chemical Physics, Computer Science::Information Theory
Abstract

Additional file 2: Figure S2. Percoll gradients of other purification method. a Accudenz gradient after 1st MACS column purification. b Percoll gradient without using MACS purification. c Percoll gradient after 1 MACS column. U upper band, M middle band, L lower band.

Published
2020
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