Uncovering host responses to malaria infection in the hematopoietic niche
Abstract/Contents
- Abstract
- Intensive malaria threatens maternal and child health among the world's most impoverished populations in the tropical and subtropical zone. Malaria is a mosquito-borne disease caused by apicomplexan parasites of the genus Plasmodium. Profound anemia is a frequent complication of severe malaria in young children living in areas of high transmission. Severe malarial anemia results from infection and destruction of RBCs in circulation and inadequate replenishment with fresh RBCs differentiated from erythroid stem cells in the bone marrow (erythropoiesis). Parasites are known to localize to the bone marrow which recent work has highlighted as a site of gametocytogenesis. How interactions between host and parasite in the bone marrow contribute to altered red cell production (dyserythropoiesis) in malaria infection remains a crucial missing piece in the current understanding of malarial pathogenesis. The research described in this dissertation addresses a substantial gap in knowledge about host-parasite interactions in the hematopoietic niche that may contribute to dyserythropoiesis. Here, an ex vivo system of erythroid differentiation from primary human bone marrow stem cells is used to investigate the stage-specific responses of developing erythroblasts to P. falciparum. Transcriptomic and proteomic approaches to analyzing infected erythroblasts at various stages of development reveal substantial disruption to programs of erythroid gene expression and induction of proteotoxic stress in response to P. falciparum. This work opens new avenues for investigating an understudied site of malaria pathogenesis and a major niche for cellular development of both host and parasite
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Feldman, Tamar Perla |
|---|---|
| Degree supervisor | Egan, Elizabeth S |
| Thesis advisor | Egan, Elizabeth S |
| Thesis advisor | Boothroyd, John C |
| Thesis advisor | Schneider, David (David Samuel) |
| Degree committee member | Boothroyd, John C |
| Degree committee member | Schneider, David (David Samuel) |
| Associated with | Stanford University, Department of Microbiology and Immunology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Tamar Perla Feldman |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology |
| Thesis | Thesis Ph.D. Stanford University 2022 |
| Location | https://purl.stanford.edu/ms540dz7491 |
Access conditions
- Copyright
- © 2022 by Tamar Perla Feldman
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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