Search

Your search keyword '"Kain, Heather"' showing total 22 results
Start Over Author "Kain, Heather"
22 results on '"Kain, Heather"'

7. 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
Full Text
View/download PDF

10. A genome-wide CRISPR-Cas9 screen identifies CENPJ as a host regulator of altered microtubule organization during Plasmodium liver infection

Author

Vijayan, Kamalakannan, primary, Arang, Nadia, additional, Wei, Ling, additional, Morrison, Robert, additional, Geiger, Rechel, additional, Parks, K. Rachael, additional, Lewis, Adam J, additional, Mast, Fred D, additional, Douglass, Alyse N, additional, Kain, Heather S, additional, Aitchison, John D, additional, Johnson, Jarrod S, additional, Aderem, Alan, additional, and Kaushansky, Alexis, additional

Published
2020
Full Text
View/download PDF

11. Liver stage malaria infection is controlled by host regulators of lipid peroxidation

Author

Kain, Heather S., primary, Glennon, Elizabeth K. K., additional, Vijayan, Kamalakannan, additional, Arang, Nadia, additional, Douglass, Alyse N., additional, Fortin, Chelsea L., additional, Zuck, Meghan, additional, Lewis, Adam J., additional, Whiteside, Samantha L., additional, Dudgeon, Denali R., additional, Johnson, Jarrod S., additional, Aderem, Alan, additional, Stevens, Kelly R., additional, and Kaushansky, Alexis, additional

Published
2019
Full Text
View/download PDF

15. A Plasmodium /-hydrolase modulates the development of invasive stages

Author

Groat-Carmona, Anna M., Kain, Heather, Brownell, Jessica, Douglass, Alyse N., Aly, Ahmed Sayed Ibrahım, Kappe, Stefan H. I., and ALY, AHMED SAYED IBRAHıM

Subjects
parasitic diseases
Abstract

The bud emergence (BEM)46 proteins are evolutionarily conserved members of the /-hydrolase superfamily, which includes enzymes with diverse functions and a wide range of substrates. Here, we identified a PlasmodiumBEM46-like protein (PBLP) and characterized it throughout the life cycle of the rodent malaria parasite Plasmodium yoelii. The PlasmodiumBEM46-like protein is shown to be closely associated with the parasite plasma membrane of asexual erythrocytic stage schizonts and exo-erythrocytic schizonts; however, PBLP localizes to unique intracellular structures in sporozoites. Generation and analysis of P.yoelii knockout (pblp) parasite lines showed that PBLP has an important role in erythrocytic stage merozoite development with pblp parasites forming fewer merozoites during schizogony, which results in decreased parasitemia when compared with wild-type (WT) parasites. pblp parasites showed no defects in gametogenesis or transmission to mosquitoes; however, because they formed fewer oocysts there was a reduction in the number of developed sporozoites in infected mosquitoes when compared with WT. Although pblp sporozoites showed no apparent defect in mosquito salivary gland infection, they showed decreased infectivity in hepatocytes in vitro. Similarly, mice infected with pblp sporozoites exhibited a delay in the onset of blood-stage patency, which is likely caused by reduced sporozoite infectivity and a discernible delay in exo-erythrocytic merozoite formation. These data are consistent with the model that PBLP has an important role in parasite invasive-stage morphogenesis throughout the parasite life cycle.

Published
2015

18. Host-based Prophylaxis Successfully Targets Liver Stage Malaria Parasites

Author

Douglass, Alyse N, primary, Kain, Heather S, additional, Abdullahi, Marian, additional, Arang, Nadia, additional, Austin, Laura S, additional, Mikolajczak, Sebastian A, additional, Billman, Zachary P, additional, Hume, Jen C C, additional, Murphy, Sean C, additional, Kappe, Stefan H I, additional, and Kaushansky, Alexis, additional

Published
2015
Full Text
View/download PDF

19. A P lasmodium α/β-hydrolase modulates the development of invasive stages.

Author

Groat‐Carmona, Anna M., Kain, Heather, Brownell, Jessica, Douglass, Alyse N., Aly, Ahmed S. I., and Kappe, Stefan H. I.

Subjects
*PLASMODIUM, *HYDROLASES, *PROTOZOAN proteins, *PROTOZOAN enzymes, *GAMETOGENESIS, *SPOROZOITES
Abstract

The bud emergence ( BEM)46 proteins are evolutionarily conserved members of the α/β-hydrolase superfamily, which includes enzymes with diverse functions and a wide range of substrates. Here, we identified a P lasmodium BEM46-like protein ( PBLP) and characterized it throughout the life cycle of the rodent malaria parasite P lasmodium yoelii. The P lasmodium BEM46-like protein is shown to be closely associated with the parasite plasma membrane of asexual erythrocytic stage schizonts and exo-erythrocytic schizonts; however, PBLP localizes to unique intracellular structures in sporozoites. Generation and analysis of P . yoelii knockout (Δ pblp) parasite lines showed that PBLP has an important role in erythrocytic stage merozoite development with Δ pblp parasites forming fewer merozoites during schizogony, which results in decreased parasitemia when compared with wild-type ( WT) parasites. Δ pblp parasites showed no defects in gametogenesis or transmission to mosquitoes; however, because they formed fewer oocysts there was a reduction in the number of developed sporozoites in infected mosquitoes when compared with WT. Although Δ pblp sporozoites showed no apparent defect in mosquito salivary gland infection, they showed decreased infectivity in hepatocytes in vitro. Similarly, mice infected with Δ pblp sporozoites exhibited a delay in the onset of blood-stage patency, which is likely caused by reduced sporozoite infectivity and a discernible delay in exo-erythrocytic merozoite formation . These data are consistent with the model that PBLP has an important role in parasite invasive-stage morphogenesis throughout the parasite life cycle. [ABSTRACT FROM AUTHOR]

Published
2015
Full Text
View/download PDF

20. A genetically engineered Plasmodium falciparumparasite vaccine provides protection from controlled human malaria infection

Author

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

Abstract

Genetically engineered live Plasmodium falciparumsporozoites constitute a potential platform for creating consistently attenuated, genetically defined, whole-parasite vaccines against malaria through targeted gene deletions. Such genetically attenuated parasites (GAPs) do not require attenuation by irradiation or concomitant drug treatment. We previously developed a P. falciparum(Pf) GAP with deletions in P52, P36, and SAP1genes (PfGAP3KO) and demonstrated its safety and immunogenicity in humans. Here, we further assessed safety, tolerability, and immunogenicity of the PfGAP3KO vaccine and tested its efficacy against controlled human malaria infection (CHMI) in malaria-naïve subjects. The vaccine was delivered by three (n= 6) or five (n= 8) immunizations with ~200 PfGAP3KO-infected mosquito bites per immunization. PfGAP3KO was safe and well tolerated with no breakthrough P. falciparumblood stage infections. Vaccine-related adverse events were predominately localized urticaria related to the numerous mosquito bites administered per vaccination. CHMI via bites with mosquitoes carrying fully infectious Pf NF54 parasites was carried out 1 month after the last immunization. Half of the study participants who received either three or five PfGAP3KO immunizations remained P. falciparumblood stage negative, as shown by a lack of detection of Plasmodium18SrRNA in the blood for 28 days after CHMI. Six protected study participants received a second CHMI 6 months later, and one remained completely protected. Thus, the PfGAP3KO vaccine was safe and immunogenic and was capable of inducing protection against sporozoite infection. These results warrant further evaluation of PfGAP3KO vaccine efficacy in dose-range finding trials with an injectable formulation.

Published
2022
Full Text
View/download PDF

21. Alterations in Phosphorylation of Hepatocyte Ribosomal Protein S6 Control PlasmodiumLiver Stage Infection

Author

Glennon, Elizabeth K.K., Austin, Laura S., Arang, Nadia, Kain, Heather S., Mast, Fred D., Vijayan, Kamalakannan, Aitchison, John D., Kappe, Stefan H.I., and Kaushansky, Alexis

Abstract

Plasmodiumparasites are highly selective when infecting hepatocytes and induce many changes within the host cell upon infection. While several host cell factors have been identified that are important for liver infection, our understanding of what facilitates the maintenance of infection remains incomplete. Here, we describe a role for phosphorylated ribosomal protein S6 (Ser235/236) (p-RPS6) in Plasmodium yoelii-infected hepatocytes. Blocking RPS6 phosphorylation prior to infection decreases the number of liver stage parasites within 24 h. Infected hepatocytes exhibit elevated levels of p-RPS6 while simultaneously abrogating the induction of phosphorylation of RPS6 in response to insulin stimulation. This is in contrast with the regulation of p-RPS6 by Toxoplasma gondii,which elevates levels of p-RPS6 after infection but does not alter the response to insulin. Our data support a model in which RPS6 phosphorylation is uncoupled from canonical regulators in Plasmodium-infected hepatocytes and is relied on by the parasite to maintain infection.

Published
2019
Full Text
View/download PDF

22. Complete attenuation of genetically engineered Plasmodium falciparumsporozoites in human subjects

Author

Kublin, James G., Mikolajczak, Sebastian A., Sack, Brandon K., Fishbaugher, Matt E., Seilie, Annette, Shelton, Lisa, VonGoedert, Tracie, Firat, Melike, Magee, Sara, Fritzen, Emma, Betz, Will, Kain, Heather S., Dankwa, Dorender A., Steel, Ryan W. J., Vaughan, Ashley M., Noah Sather, D., Murphy, Sean C., and Kappe, Stefan H. I.

Abstract

A genetically attenuated Plasmodium falciparumstrain called Pf GAP3KO is completely attenuated, safe, and immunogenic in adults.

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results