Malaria has undergone a striking expansion in recent years, both its range and mortality, due in part to the appearance of multiple drug resistant strains of Plasmodium falciparum. The re-emergence of malaria in regions where it had been eradicated of special concern to health official. Despite the magnitude of the problem, the mechanism(s) of parasite resistance to the majority of anti-malarial drugs are not clearly understood. The experiments outlined in this proposal will examine the molecular basis of drug resistance using the rodent malaria species Plasmodium berghei. Emphasis will be placed on homologous of mdr genes have been implicated in treatment failures of mammalian neoplastic cells.
The specific aims are: (1) to establish the role of the multi-drug resistance (pbmdr1) gene in P. berghei through gene disruption and localization of the gene product; and (2) to identify novel genes potentially involved in malaria drug resistance, including the genes encoding the role of the rodent malaria P. berghei mdr1 gene, the reading frame will be disrupted by transfection and the resulting pattern of drug resistance will be assayed. Furthermore, the expression and intracellular localization of the protein will be investigated. Other candidate genes (mrp and ggcs) will be identified using the polymerase chain reaction and degenerate primers based on highly conserved sequences. The potential association of these gene fragments with drug resistance will be investigated in a collection of drug sensitive and multi-drug resistant lines of P. berghei.

Project Start
2001-08-01
Project End
2002-07-31
Budget Start
Budget End
Support Year
17
Fiscal Year
2001
Total Cost
Indirect Cost
Name
University of Puerto Rico Med Sciences
Department
Type
DUNS #
City
San Juan
State
PR
Country
United States
Zip Code
00936
Rijpma, Sanna R; van der Velden, Maarten; González-Pons, Maria et al. (2016) Multidrug ATP-binding cassette transporters are essential for hepatic development of Plasmodium sporozoites. Cell Microbiol 18:369-83
Padín-Irizarry, Vivian; Colón-Lorenzo, Emilee E; Vega-Rodríguez, Joel et al. (2016) Glutathione-deficient Plasmodium berghei parasites exhibit growth delay and nuclear DNA damage. Free Radic Biol Med 95:43-54
Jardón, Javier; Izquierdo, Natalio J; Renta, Jessica Y et al. (2016) Ocular Findings in Patients with the Hermansky-Pudlak Syndrome (Types 1 and 3). Ophthalmic Genet 37:89-94
Rivera-Peña, Bianca; Ruíz-Fullana, Francisco J; Vélez-Reyes, Germán L et al. (2016) HPV-16 infection modifies overall survival of Puerto Rican HNSCC patients. Infect Agent Cancer 11:47
Velásquez-Martínez, Maria C; Vázquez-Torres, Rafael; Rojas, Legier V et al. (2015) Alpha-1 adrenoreceptors modulate GABA release onto ventral tegmental area dopamine neurons. Neuropharmacology 88:110-21
Vega-Rodríguez, Joel; Pastrana-Mena, Rebecca; Crespo-Lladó, Keila N et al. (2015) Implications of Glutathione Levels in the Plasmodium berghei Response to Chloroquine and Artemisinin. PLoS One 10:e0128212
Zenón, Frances; Cantres-Rosario, Yisel; Adiga, Radhika et al. (2015) HIV-infected microglia mediate cathepsin B-induced neurotoxicity. J Neurovirol 21:544-58
Ortiz, A P; Unger, E R; Muñoz, C et al. (2014) Cross-sectional study of HPV-16 infection in a population-based subsample of Hispanic adults. BMJ Open 4:e004203
Rosas, Odrick R; Torrado, Aranza I; Santiago, Jose M et al. (2014) Long-term treatment with PP2 after spinal cord injury resulted in functional locomotor recovery and increased spared tissue. Neural Regen Res 9:2164-73
Mosquera, Laurivette; Colón, Jennifer M; Santiago, José M et al. (2014) Tamoxifen and estradiol improved locomotor function and increased spared tissue in rats after spinal cord injury: their antioxidant effect and role of estrogen receptor alpha. Brain Res 1561:11-22

Showing the most recent 10 out of 174 publications