A5009862516- Malaria Research and Control
- HIV/AIDS drug development and treatment
- Mosquito-borne diseases and control
- Synthesis and Characterization of Heterocyclic Compounds
- RNA and protein synthesis mechanisms
- Aquaculture disease management and microbiota
- Synthesis and Biological Evaluation
- Crystallization and Solubility Studies
- Synthesis and biological activity
- Click Chemistry and Applications
- Drug Transport and Resistance Mechanisms
- Antibiotic Resistance in Bacteria
- Research on Leishmaniasis Studies
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- X-ray Diffraction in Crystallography
- Computational Drug Discovery Methods
- Trypanosoma species research and implications
Pennsylvania State University
2021-2025
University of Notre Dame
2024
Development of antimalarial compounds into clinical candidates remains costly and arduous without detailed knowledge the target. As resistance increases treatment options at various stages disease are limited, it is critical to identify multistage drug targets that readily interrogated in biochemical assays. Whole-genome sequencing 18 parasite clones evolved using thienopyrimidine with submicromolar, rapid-killing, pan-life cycle antiparasitic activity showed all had acquired mutations P....
Compounds acting on multiple targets are critical to combating antimalarial drug resistance. Here, we report that the human “mammalian target of rapamycin” (mTOR) inhibitor sapanisertib has potent prophylactic liver stage activity, in vitro and vivo asexual blood (ABS) transmission-blocking activity against protozoan parasite Plasmodium spp. Chemoproteomics studies revealed potential kinase targets, inhibition phosphatidylinositol 4-kinase type III beta (PI4Kβ) cyclic guanosine...
New compounds targeting human malaria parasites are critical for effective control and elimination. Here, we pursued the imidazoquinolinone AZD0156 (MMV1580483), a ataxia‐telangiectasia mutated (ATM) kinase inhibitor that completed Phase I clinical trials as an anticancer agent. We validated its in vitro activity against two main forms of Plasmodium falciparum parasite host, viz. asexual blood (symptomatic) stage sexual gametocyte (transmission) stage. Resistance selection, cross‐resistance,...
The emergence of Plasmodium falciparum parasite resistance to dihydroartemisinin + piperaquine (PPQ) in Southeast Asia threatens plans increase the global use this first-line antimalarial combination. High-level PPQ appears be mediated primarily by novel mutations P . chloroquine transporter (PfCRT), which enhance survival at high concentrations vitro and risk treatment failure patients. Using isogenic Dd2 parasites expressing contemporary pfcrt alleles with differential susceptibilities, we...
New compounds targeting human malaria parasites are critical for effective control and elimination. Here, we pursued the imidazoquinolinone AZD0156 (MMV1580483), a ataxia‐telangiectasia mutated (ATM) kinase inhibitor that completed Phase I clinical trials as an anticancer agent. We validated its in vitro activity against two main forms of Plasmodium falciparum parasite host, viz. asexual blood (symptomatic) stage sexual gametocyte (transmission) stage. Resistance selection, cross‐resistance,...
Our study leverages gene editing techniques in Plasmodium falciparum asexual blood stage parasites to profile novel mutations mutant PfCRT, an important mediator of piperaquine resistance, which developed Southeast Asian field isolates or cultured for long periods time. We provide evidence that increased parasite fitness these lines is the primary driver emergence PfCRT variants. These differentially impact susceptibility and chloroquine, highlighting multifaceted effects single point this...
Artemisinin partial resistance (ART-R) has spread throughout Southeast Asia and mutations in