A5066149180- Malaria Research and Control
- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Mosquito-borne diseases and control
- Helicobacter pylori-related gastroenterology studies
- HIV/AIDS drug development and treatment
- Computational Drug Discovery Methods
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Immune responses and vaccinations
- Metabolomics and Mass Spectrometry Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Insect Resistance and Genetics
- Vector-borne infectious diseases
- Research on Leishmaniasis Studies
- Biochemical and Molecular Research
- Cancer-related gene regulation
- Invertebrate Immune Response Mechanisms
- HIV Research and Treatment
- Toxoplasma gondii Research Studies
- Immune cells in cancer
- Drug-Induced Hepatotoxicity and Protection
New York State College of Veterinary Medicine
2024-2025
Cornell University
2024-2025
University of Glasgow
2018-2023
Wellcome Centre for Molecular Parasitology
2018-2023
The eukaryotic Glucose Induced Degradation/C-Terminal to LisH (GID/CTLH) complex is a highly conserved E3 ubiquitin ligase involved in broad range of biological processes. However, role this host anti-microbial defenses has not been described. We exploited Mycobacterium tuberculosis (Mtb) induced cytotoxicity macrophages FACS based CRISPR genetic screen identify determinants intracellular Mtb growth restriction. Our identified 5 (GID8, YPEL5, WDR26, UBE2H, MAEA) the 12 predicted members...
Targeting parasite's protein kinase Malaria elimination goals are constantly eroded by the challenge of emerging drug and insecticide resistance. Alam et al. have taken established targets—CLK kinases involved in regulation RNA splicing—and investigated how inhibition enzymes blocks completion its complex life cycle. They identified an inhibitor CLK that was 100-fold less active against most closely related human effective at clearing rodent malaria parasites. Not only does this compound...
Mycobacterium tuberculosis ( Mtb ) infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular utilize host derived lipids maintain infection, the role macrophage processing on bacteria’s ability access pool remains undefined. We utilized a CRISPR-Cas9 genetic approach assess impact sequential steps in fatty acid growth . Our analyzes demonstrate which cannot either import, store or catabolize acids restrict by both common...
Mycobacterium tuberculosis ( Mtb ) infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular utilize host-derived lipids maintain infection, the role macrophage processing on bacteria’s ability access pool remains undefined. We utilized a CRISPR-Cas9 genetic approach assess impact sequential steps in fatty acid growth . Our analyses demonstrate cannot either import, store, or catabolize acids restrict by both common and...
As resistance to artemisinins (current frontline drugs in malaria treatment) emerges Southeast Asia, there is an urgent need identify the genetic determinants and understand molecular mechanisms underpinning such resistance. Such insights could lead prospective interventions contain prevent eventual spread other regions where endemic. Reduced susceptibility artemisinin Asia has been primarily linked mutations Plasmodium falciparum Kelch-13 gene, which currently widely recognized as a marker of
Recent successes in malaria control have been seriously threatened by the emergence of Plasmodium falciparum parasite resistance to frontline artemisinin drugs Southeast Asia. P. is associated with mutations K13 protein, which associates a delay time required clear parasites upon drug treatment. Gene editing technologies used validate role several candidate mediating vitro under laboratory conditions. Nonetheless, causal these vivo conditions has matter debate. Here, we CRISPR/Cas9 gene...
The eukaryotic GID/CTLH complex is a highly conserved E3 ubiquitin ligase involved in broad range of biological processes. However, role this host antimicrobial defenses has not been described. We exploited
Abstract Mycobacterium tuberculosis ( Mtb ) infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular utilize host derived lipids maintain infection, the role macrophage processing on bacteria’s ability access pool remains undefined. We utilized a CRISPR-Cas9 genetic approach assess impact sequential steps in fatty acid growth . Our analyzes demonstrate which cannot either import, store or catabolize acids restrict by...
The ubiquitin proteasome system (UPS) is an emerging drug target in malaria due to its essential role the parasite's life cycle stages as well contribution resistance artemisinins. Polymorphisms Kelch13 gene of Plasmodium falciparum are primary markers artemisinin and among other things phenotypically characterized by overactive UPS. Inhibitors targeting proteasome, critical components UPS, display activity parasites synergize action. Here we report small molecule inhibitors mammalian...
Abstract The requirement for next generation anti-malarials to be both curative and transmission blockers necessitate the identification of molecular pathways essential viability asexual sexual parasite life stages. Here we identify a selective inhibitor Plasmodium falciparum protein kinase Pf CLK3 which use in combination with chemogenetics, whole genome sequencing transcriptomics validate as druggable target acting at multiple Consistent proposed role regulator RNA splicing, inhibition...
Mycobacterium tuberculosis ( Mtb ) infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular utilize host-derived lipids maintain infection, the role macrophage processing on bacteria’s ability access pool remains undefined. We utilized a CRISPR-Cas9 genetic approach assess impact sequential steps in fatty acid growth . Our analyses demonstrate cannot either import, store, or catabolize acids restrict by both common and...
Mycobacterium tuberculosis ( Mtb ) infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular utilize host derived lipids maintain infection, the role macrophage processing on bacteria’s ability access pool remains undefined. We utilized a CRISPR-Cas9 genetic approach assess impact sequential steps in fatty acid growth . Our analyzes demonstrate mutated cannot either import, store or catabolize acids restrict by both...
ABSTRACT Characterizing the mode of action anti-malarial compounds that emerge from high-throughput phenotypic screens is central to understanding how parasite resistance these drugs can emerge. Here, we have employed untargeted metabolomics inform on mechanism leads with different speed kill profiles being developed by Novartis Institute Tropical Diseases (NITD). Time-resolved global changes in malaria metabolite upon drug treatment were quantified using liquid chromatography-based mass...
Abstract As resistance to artemisinins (current frontline drugs in malaria treatment) emerges south East Asia (SEA), there is an urgent need identify the genetic determinants and understand molecular mechanisms underpinning such resistance. Such insights could lead prospective interventions contain prevent eventual spread other endemic regions. Artemisinin reduced susceptibility SEA has been primarily linked mutations P. falciparum Kelch13, which currently widely recognised as a marker of...
Abstract Current malaria control efforts rely significantly on artemisinin combinational therapies which have played massive roles in alleviating the global burden of disease. Emergence resistance to artemisinins is therefore, not just alarming but requires immediate intervention points such as development new antimalarial drugs or improvement current through adjuvant combination therapies. Artemisinin primarily conferred by Kelch13 propeller mutations are phenotypically characterised...
ABSTRACT The recent emergence of Plasmodium falciparum (PF) parasite resistance to the first line antimalarial drug artemisinin is particular concern. Artemisinin primarily driven by mutations in PF K13 protein, which enhance survival early ring stage parasites treated with active metabolite dihydroartemisinin vitro and associate delayed clearance vivo . However, association has been problematic due absence a tractable model. Herein, we have employed CRISPR/Cas9 genome editing engineer...
Abstract Characterizing the mode of action antimalarial compounds that emerge from high-throughput phenotypic screens is central to understanding how parasite resistance these drugs can emerge. Here, we have employed untargeted metabolomics inform on mechanism leads with different speed kill profiles being developed by Novartis Institute Tropical Diseases (NITD). Time-resolved global changes in malaria metabolite upon drug treatment were quantified using liquid chromatography-based mass...