A5033955812- Trypanosoma species research and implications
- Synthesis and Biological Evaluation
- Research on Leishmaniasis Studies
- RNA and protein synthesis mechanisms
- Malaria Research and Control
- Biochemical and Molecular Research
- RNA Interference and Gene Delivery
- Antimicrobial Peptides and Activities
- Quinazolinone synthesis and applications
- Parasitic Infections and Diagnostics
- Bacterial Genetics and Biotechnology
- Microfluidic and Capillary Electrophoresis Applications
- Insect Pest Control Strategies
- RNA modifications and cancer
- Cytomegalovirus and herpesvirus research
- Digital Holography and Microscopy
- Electrohydrodynamics and Fluid Dynamics
- Protein Structure and Dynamics
- Advanced Fluorescence Microscopy Techniques
- Advanced Optical Imaging Technologies
- Invertebrate Immune Response Mechanisms
- Plant Virus Research Studies
- Coccidia and coccidiosis research
- Parasites and Host Interactions
- Microfluidic and Bio-sensing Technologies
New York University
2013-2025
Washington University in St. Louis
2018-2024
New York Proton Center
2014
Institute of Parasitology
2014
University School
2014
Tropical protozoal infections are a significant cause of morbidity and mortality worldwide; four in particular (human African trypanosomiasis (HAT), Chagas disease, cutaneous leishmaniasis, malaria) have an estimated combined burden over 87 million disability-adjusted life years. New drugs needed for each these diseases. Building on the previous identification NEU-617 (1) as potent nontoxic inhibitor proliferation HAT pathogen (Trypanosoma brucei), we now tested this class analogs against...
Chagas disease is caused by the intracellular protozoan parasite Trypanosomal cruzi, and current drugs are lacking in terms of desired safety efficacy profiles. Following on a recently reported high-throughput screening campaign, we have explored initial structure–activity relationships around class imidazole-based compounds. This profiling has uncovered compounds 4c (NEU321) 4j (NEU704), which potent against vitro cultures T. cruzi greater than 160-fold selective over host cells. We report...
Hesperadin, an established human Aurora B inhibitor, was tested against cultures of <italic>Trypanosoma brucei</italic>, <italic>Leishmania major</italic>, and <italic>Plasmodium falciparum</italic>, identified to be a potent proliferation inhibitor.
A simple microfluidic device efficiently sorts a mixture of different sized particles and traps them into specific positions.
We demonstrate a compact portable imaging system for the detection of waterborne parasites in resource-limited settings. The previously demonstrated sub-pixel sweeping microscopy (SPSM) technique is lens-less scheme that can achieve high-resolution (<1 µm) bright-field over large field-of-view (5.7 mm×4.3 mm). A chip-scale microscope system, based on SPSM technique, be used automated and high-throughput protozoan parasite cysts effective diagnosis enteric infection. successfully imaged...
The repurposing of human tyrosine kinase inhibitor scaffolds for generation antiparasitic agents has provided new lead compounds tropical diseases.
A kinase-targeting cell-based high-throughput screen (HTS) against Trypanosoma brucei was recently reported, and this screening set included the Published Kinase Inhibitor Set (PKIS). From PKIS identified 53 compounds with pEC50 ≥ 6. Utilizing published data available for PKIS, a statistical analysis of these active antiparasitic performed, allowing identification human kinases having inhibitors that show high likelihood blocking T. cellular proliferation in vitro. This observation confirmed...
is a causative agent of human malaria. Sixty percent mRNAs from its extremely AT-rich (81%) genome harbor long polyadenosine (polyA) runs within their ORFs, distinguishing the parasite hosts and other sequenced organisms. Recent studies indicate polyA cause ribosome stalling frameshifting, triggering mRNA surveillance pathways attenuating protein synthesis. Here, we show that
Utilizing a target repurposing and parasite-hopping approach, we tested previously reported library of compounds that were active against Trypanosoma brucei, plus 31 new compounds, variety protozoan parasites including cruzi, Leishmania major, donovani, Plasmodium falciparum. This led to the discovery several with submicromolar activities improved physicochemical properties are early leads toward development chemotherapeutic agents kinetoplastid diseases malaria.
Plasmodium falciparum, the malaria-causing parasite, is a leading cause of infection-induced deaths worldwide. The preferred treatment approach artemisinin-based combination therapy, which couples fast-acting artemisinin derivatives with longer-acting drugs, such as lumefantrine, mefloquine, and amodiaquine. However, urgency for new treatments has risen due to parasite's growing resistance existing therapies. In this study, common characteristic P. falciparum proteome—stretches poly-lysine...
Neglected tropical diseases such as Chagas disease, human African trypanosomiasis, leishmaniasis, and schistosomiasis have a significant global health impact in predominantly developing countries, although these are spreading due to increased international travel population migration. Drug repurposing with focus on increasing antiparasitic potency drug-like properties is cost-effective efficient route the development of new therapies. Here we identify compounds that potent activity against...
Human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis present a significant burden across the developing world. Existing therapeutics for these protozoal neglected tropical diseases suffer from severe side effects toxicity. Previously, NEU-1045 (3) was identified as promising lead with cross-pathogen activity, though it possessed poor physicochemical properties. We have designed library of analogues improved calculated properties built on quinoline scaffold 3 incorporating...
The capability to perform multicolor, wide field-of-view (FOV) fluorescence microscopy imaging is important in screening and pathology applications. We developed a microscopic slide-imaging system that can achieve FOV, based on the Talbot effect. In this system, light-spot grid generated by effect illuminates sample. By tilting excitation beam, Talbot-focused spot scans across images are reconstructed collecting emissions correspond each focused with relay optics arrangement. prototype...
Discovery of new chemotherapeutic lead agents can be accelerated by optimizing chemotypes proven to effective in other diseases act against parasites. One such medicinal chemistry campaign has focused on the anilinoquinazoline drug lapatinib (1) and alkynyl thieno[3,2-d]pyrimidine hit GW837016X (NEU-391, 3) into leads for antitrypanosome drugs. We now report structure–activity relationship studies 3 its analogs Trypanosoma brucei, which causes human African trypanosomiasis (HAT). The series...
We recently reported the medicinal chemistry re-optimization of a series compounds derived from human tyrosine kinase inhibitor, lapatinib, for activity against Plasmodium falciparum. From this same library compounds, we now report potent Trypanosoma brucei (which causes African trypanosomiasis), T. cruzi (the pathogen that Chagas disease), and Leishmania spp. cause leishmaniasis). In addition, sub-micromolar were identified inhibit proliferation parasites animal trypanosomiasis, congolense...
ABSTRACT Widespread resistance to most antimalaria drugs in use has prompted the search for novel candidate compounds with activity against Plasmodium asexual blood stages be developed treatment. In addition, current malaria eradication programs require development of that are effective all parasite life cycle. We have analyzed antimalarial properties xenomycins, a subclass small molecule initially isolated anticancer and similarity quinacrine biological effects on mammalian cells. vitro...
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. It endemic in South and Central America recently has been found other parts of world, due to migration chronically infected patients. The current treatment for not satisfactory, there a need new treatments. In this work, we describe optimization hit compound resulting from phenotypic screen library compounds against T. series was optimized level where it had satisfactory pharmacokinetics allow an efficacy study mouse model...
Ribosomes are macromolecular RNA-protein complexes that constitute the central machinery responsible for protein synthesis and quality control in cell. also serve as a hub multiple non-ribosomal proteins RNAs synthesis. However, purification of ribosomes associated factors functional structural studies requires large amount starting biological material tedious workflow. Current methods challenging they combine ultracentrifugation, use sucrose cushions or gradients, expensive equipment, hours...
The receptor for activated C-kinase 1 (RACK1), a highly conserved eukaryotic protein, is known to have many varying biological roles and functions. Previous work has established RACK1 as ribosomal with defined regions important ribosome binding in cells. In Plasmodium falciparum, been shown be required parasite growth, however, conflicting evidence presented about its role mRNA translation. Given the importance of regulatory component translation quality control, case could made parasites...
Abstract Plasmodium falciparum , the causative agent of human malaria, is an apicomplexan parasite with a complex, multi-host life cycle. Sixty percent transcripts from its extreme AT-rich (81%) genome possess coding polyadenosine (polyA) runs, distinguishing hosts and other sequenced organisms. Recent studies indicate that polyA runs encoding poly-lysine are hot spots for ribosome stalling frameshifting, eliciting mRNA surveillance pathways attenuating protein synthesis in majority...