A5057207686- Toxoplasma gondii Research Studies
- Malaria Research and Control
- Microbial Natural Products and Biosynthesis
- HIV Research and Treatment
- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Research on Leishmaniasis Studies
- Invertebrate Immune Response Mechanisms
- Heme Oxygenase-1 and Carbon Monoxide
- Melanoma and MAPK Pathways
- Folate and B Vitamins Research
- Cancer-related Molecular Pathways
- HER2/EGFR in Cancer Research
- HIV/AIDS drug development and treatment
- Metabolism and Genetic Disorders
- Cancer therapeutics and mechanisms
- Genetics and Neurodevelopmental Disorders
- Restraint-Related Deaths
- Lung Cancer Treatments and Mutations
- Ubiquitin and proteasome pathways
- Tuberculosis Research and Epidemiology
- Cytomegalovirus and herpesvirus research
Schrodinger (United States)
2021-2025
Stanford University
2018-2019
Stanford Medicine
2017
The malaria parasite Plasmodium falciparum and related apicomplexan pathogens contain an essential plastid organelle, the apicoplast, which is a key anti-parasitic target. Derived from secondary endosymbiosis, apicoplast depends on novel, but largely cryptic, mechanisms for protein/lipid import organelle inheritance during replication. These critical biogenesis pathways present untapped opportunities to discover new parasite-specific drug targets. We used innovative screen identify actinonin...
Endosymbiosis has driven major molecular and cellular innovations. Plasmodium spp. parasites that cause malaria contain an essential, non-photosynthetic plastid-the apicoplast-which originated from a secondary (eukaryote-eukaryote) endosymbiosis. To discover organellar pathways with evolutionary biomedical significance, we performed mutagenesis screen for essential genes required apicoplast biogenesis in falciparum. Apicoplast(-) mutants were isolated using chemical rescue permits...
Drug resistance is a critical challenge in treating diseases like cancer and infectious disease. This study presents novel computational workflow for predicting on-target mutations to small molecule inhibitors (SMIs). The approach integrates genetic models with alchemical free energy perturbation (FEP+) calculations identify likely mutations. Specifically, model, RECODE, leverages cancer-specific mutation patterns prioritize probable amino acid changes. Physics-based assess the impact of...
Despite the success of first, second and third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in treatment non-small cell lung cancer (NSCLC) with classical EGFR mutations (L858R or Exon 19 deletions), disease progression often occurs due to acquisition additional domain that confer TKI resistance. Specifically, both T790M C797S resistance results an variant is resistant all approved TKIs. Herein, we report a physics-based computationally-driven lead...
Toxoplasma gondii and related human parasites contain an essential plastid organelle called the apicoplast. Clinically used antibiotics other inhibitors that disrupt apicoplast biogenesis cause a mysterious "delayed-death" phenotype in which parasite growth is unaffected during first lytic cycle of inhibitor treatment but severely inhibited second even after drug removal. Critical to understanding complex downstream cellular effects these classes are timing loss how it relates this peculiar...
This work defines the function of an enzyme in obligate intracellular parasite Toxoplasma gondii . We show that this previously uncharacterized is critical for aspects cellular division by and loss leads to parasites with cell defects which also are disorganized inside their vacuoles. ability disseminate from site infection may have a significant impact on parasite's overall infectivity host organism.
Summary Endosymbiosis has driven major molecular and cellular innovations. Plasmodium spp. parasites that cause malaria contain an essential, non-photosynthetic plastid, the apicoplast, which originated from a secondary (eukaryote-eukaryote) endosymbiosis. To discover organellar pathways with evolutionary biomedical significance, we performed mutagenesis screen for essential genes required apicoplast biogenesis in P. falciparum . Apicoplast-minus mutants were isolated using chemical rescue...
Drug resistance is a critical challenge in treating diseases like cancer and infectious disease. This study presents novel computational workflow for predicting on-target mutations to small molecule inhibitors (SMIs). The approach integrates genetic models with alchemical free energy perturbation (FEP+) calculations identify likely mutations. Specifically, model, RECODE, leverages cancer-specific mutation patterns prioritize probable amino acid changes. Physics-based assess the impact of...
Despite the success of first, second, and third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer with classical EGFR mutations (L858R or Exon 19 deletions), disease progression occurs due to acquisition T790M C797S resistance. Herein, we report a physics-based computationally driven lead identification approach that identified structurally unique imidazo[3.2-
The malaria parasite Plasmodium falciparum and related apicomplexan pathogens contain an essential plastid organelle, the apicoplast, which is a key anti-parasitic target. Derived from secondary endosymbiosis, apicoplast depends on novel, but largely cryptic, mechanisms for protein/lipid import organelle inheritance during replication. These critical biogenesis pathways present untapped opportunities to discover new parasite-specific drug targets. We used innovative screen identify actinonin...
Abstract Introduction: Ubiquitin-specific protease 7 (USP7) is a deubiquitinase that regulates several proteins involved in cell cycle, DNA repair, genomic stability, and epigenetics has been implicated cancer progression. A key substrate of USP7 MDM2, the oncogenic E3 ubiquitin ligase promotes degradation tumor suppressor p53. USP7-mediated stabilization MDM2 leads to p53, preventing cycle arrest induction apoptosis promoting growth. In addition MDM2-p53 pathway, number other substrates...
Abstract Toxoplasma gondii and related human parasites contain an essential plastid organelle called the apicoplast. Clinically-used antibiotics other inhibitors that disrupt apicoplast biogenesis cause a mysterious “delayed-death” phenotype, in which parasite growth is unaffected during first lytic cycle of inhibitor treatment but severely inhibited second even after drug removal. Critical to understanding complex downstream cellular effects these classes timing loss how it relates this...