Abstract

The overall goals of this proposal are to complete the structural analysis of the GPI anchors of the proteins of P. falciparum, identify unusual substituents, relate specific structural features to immunogenecity and aspects of disease pathology and to define effects of the inhibition of GPI synthesis on the parasite. We have shown that GPI anchor synthesis is the major carbohydrate- related protein modification carried out by the parasite and, that N- linked glycosylation is of very low frequency and that O-linked glycosylation is either completely absent or at extremely low levels. In addition, inhibition of GPI synthesis is strongly inhibitory to the parasite suggesting a target for anti-malarial drug development.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI041139-03
Application #
6137220
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Program Officer
Fairfield, Alexandra
Project Start
1998-01-15
Project End
2001-05-31
Budget Start
2000-01-01
Budget End
2001-05-31
Support Year
3
Fiscal Year
2000
Total Cost
$280,380
Indirect Cost

  Institution

Name
Georgetown University
Department
Biochemistry
Type
Schools of Dentistry
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057

  Publications

Wu, Xianzhu; Gowda, Nagaraj M; Kawasawa, Yuka I et al. (2018) A malaria protein factor induces IL-4 production by dendritic cells via PI3K-Akt-NF-?B signaling independent of MyD88/TRIF and promotes Th2 response. J Biol Chem 293:10425-10434
Wu, Xianzhu; Dayanand, Kiran K; Thylur, Ramesh P et al. (2017) Small molecule-based inhibition of MEK1/2 proteins dampens inflammatory responses to malaria, reduces parasite load, and mitigates pathogenic outcomes. J Biol Chem 292:13615-13634
Thylur, Ramesh P; Wu, Xianzhu; Gowda, Nagaraj M et al. (2017) CD36 receptor regulates malaria-induced immune responses primarily at early blood stage infection contributing to parasitemia control and resistance to mortality. J Biol Chem 292:9394-9408
Yao, Xiangyu; Wu, Jian; Lin, Meng et al. (2016) Increased CD40 Expression Enhances Early STING-Mediated Type I Interferon Response and Host Survival in a Rodent Malaria Model. PLoS Pathog 12:e1005930
Sadashiva, Maralinganadoddi P; Gowda, Raghavendra; Wu, Xianzhu et al. (2015) A non-cytotoxic N-dehydroabietylamine derivative with potent antimalarial activity. Exp Parasitol 155:68-73
Wu, Xianzhu; Gowda, Nagaraj M; Gowda, D Channe (2015) Phagosomal Acidification Prevents Macrophage Inflammatory Cytokine Production to Malaria, and Dendritic Cells Are the Major Source at the Early Stages of Infection: IMPLICATION FOR MALARIA PROTECTIVE IMMUNITY DEVELOPMENT. J Biol Chem 290:23135-47
Bhavanandan, Veer P; Gowda, D Channe (2014) Introduction to the complexity of cell surface and tissue matrix glycoconjugates. Adv Neurobiol 9:1-31
Gowda, Nagaraj M; Wu, Xianzhu; Kumar, Sanjeev et al. (2013) CD36 contributes to malaria parasite-induced pro-inflammatory cytokine production and NK and T cell activation by dendritic cells. PLoS One 8:e77604
Zhu, Xiaotong; Pan, Yanyan; Li, Ying et al. (2012) Targeting Toll-like receptors by chloroquine protects mice from experimental cerebral malaria. Int Immunopharmacol 13:392-7
Zhu, Jianzhong; Weinberg, Rebecca; Wu, Xianzhu et al. (2012) I?b-? plays an important role in the ERK-dependent dysregulation of malaria parasite GPI-induced IL-12 expression. IUBMB Life 64:187-93

Showing the most recent 10 out of 29 publications