A5049054709- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Genomics and Phylogenetic Studies
- Genome Rearrangement Algorithms
- Microbial Community Ecology and Physiology
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Protist diversity and phylogeny
- Signaling Pathways in Disease
- Asthma and respiratory diseases
- Renal and related cancers
- Parasitic Infections and Diagnostics
- Photosynthetic Processes and Mechanisms
- Adenosine and Purinergic Signaling
- Food Allergy and Anaphylaxis Research
- Insect Resistance and Genetics
- Plant Virus Research Studies
- Cell Adhesion Molecules Research
- Cancer Immunotherapy and Biomarkers
- Insect symbiosis and bacterial influences
- Renal Diseases and Glomerulopathies
- RNA and protein synthesis mechanisms
- Eosinophilic Disorders and Syndromes
- Genetic Associations and Epidemiology
- Galectins and Cancer Biology
Pfizer (United States)
2024
Infectious Disease Research Institute
2019-2023
University of Washington Medical Center
2019-2022
University of Washington
2018-2022
The Ohio State University
2020
Universidade Federal de São Paulo
2020
Weatherford College
2020
Seattle University
2019
Center for Infectious Disease Research
2018
Significance Statement The absence of high-resolution epigenomic maps key kidney cell types has hampered understanding kidney-specific genome regulation in health and disease. Kidney-associated genetic variants, identified genome-wide association studies, are concentrated accessible chromatin regions containing regulatory DNA elements. authors describe the generation initial characterization paired these gene expression profiles cells from primary human glomerular cortex cultures. By...
Leishmania parasites cause a variety of serious human diseases, with no effective vaccine and emerging resistance to current drug therapy. We have previously shown that novel DNA base called J is critical for transcription termination at the ends polycistronic gene clusters are hallmark related trypanosomatids.
ABSTRACT Euglenoids (Euglenida) are unicellular flagellates possessing exceptionally wide geographical and ecological distribution. combine a biotechnological potential with unique position in the eukaryotic tree of life. In large part these microbes owe this success to diverse genetics including secondary endosymbiosis likely additional sources genes. Multiple euglenoid species have translational applications show great promise production biofuels, nutraceuticals, bioremediation, cancer...
In this study, we report that the ability of human pathogen Leishmania to sense and monitor lack arginine in phagolysosome host macrophage is essential for disease development. Phagolysosomes macrophages are niche where resides causes leishmaniasis. During infection, concentration decreases as part innate immune response. An sensor on cell surface activates an deprivation response pathway upregulates expression a parasite transporter (AAP3). Here, use CRISPR/Cas9-mediated disruption AAP3...
African trypanosomes, the protozoan agent of human trypanosomaisis, avoid host immune system by switching expression variant surface glycoprotein (VSG). VSG is a long-lived protein that has long been thought to be turned over hydrolysis its glycolipid membrane anchor.
Monoallelic exclusion ensures that the African trypanosome Trypanosoma brucei exclusively expresses only 1 of thousands different variant surface glycoprotein (VSG) coat genes. The active VSG is transcribed from 15 polycistronic bloodstream-form expression sites (ESs), which are controlled in a mutually exclusive fashion. Unusually, T. uses RNA polymerase I (Pol I) to transcribe ES, unprecedented among eukaryotes. This ES located within unique extranucleolar Pol body called expression-site...
Eukaryotes use histone variants and post-translation modifications (PTMs), as well DNA base modifications, to regulate replication/repair, chromosome condensation, gene expression. Despite the unusual organization of their protein-coding genes into large polycistronic transcription units (PTUs), trypanosomatid parasites also employ a "histone code" control these processes, but details this epigenetic code are poorly understood. Here, we present results experiments designed elucidate...
Human infection with the protozoan parasite Trypanosoma cruzi causes Chagas disease for which there are no prophylactic vaccines. Cyclophilin 19 is a secreted cis-trans peptidyl isomerase expressed in all life stages of cruzi. This protein insect stage leads to inactivation anti-parasitic peptides and transformation whereas intracellular amastigotes it participates generating ROS promoting growth parasites. We have generated mutant depleted expression Cyp19 by removal 2 3 genes encoding this...
Abstract Background Studying a new species using high-throughput sequencing requires high-quality reference genome. However, assembling chromosome length sequences remains challenging. Recent advances in chromatin conformation capture (Hi-C) have provided approach to scaffolding genome assemblies, and the last ten years seen proliferation of such methods. our knowledge no comprehensive benchmarking Hi-C scaffolders has been conducted date. Results Through literature review we identified most...
<h3>Background</h3> Vedotin antibody-drug conjugates (ADCs), which incorporate the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable peptide linker, elicit antitumor activity through multiple potential mechanisms of action including MMAE-mediated cytotoxicity and immunogenic cell death (ICD). Mounting preclinical clinical evidence suggests combination vedotin ADC plus anti-PD1 immunotherapy elicits clinically meaningful responses. Using mouse model...
Abstract Arginine homeostasis in lysosomes is critical for growth and metabolism of mammalian cells. They employ a specific sensor (SLC38A9) that monitors intra-lysosome arginine sufficiency subsequently up-regulates cellular mTORC1 activity. Lysosomes macrophages (phagolysosomes) are the niche where parasitic protozoan Leishmania resides causes important human disease. Several years ago, we discovered upon starvation, cultured parasites promptly activate MAPK2-mediated Deprivation Response...
Abstract Unlike most other eukaryotes, Leishmania and trypanosomatid protozoa have largely eschewed transcriptional control of gene expression; relying instead on post-transcriptional regulation mRNAs derived from polycistronic transcription units (PTUs). In these parasites, a novel modified nucleotide base (β-D-glucopyranosyloxymethyluracil) known as J plays critical role in ensuring that termination occurs only at the end each PTU, rather than polyadenylation sites individual genes. To...
Abstract Trypanosoma cruzi is the etiologic agent of Chagas disease for which there are no prophylactic vaccines. Cyclophilin 19 a secreted cis-trans peptidyl isomerase expressed in all life stages , insect stage leads to inactivation anti-parasitic peptides and parasite transformation intracellular amastigotes participates generating ROS enhancing growth. We have generated knock-out mutant Cyp19 fails replicate cell culture or mice indicating that lack critical infectivity. Knock-out...
Abstract teaserEuglenoids show great promise to benefit our world; as biofuels, environmental remediators, anti-cancer agents, robotics design simulators and food nutritional but the absence of reference genomes currently limit realizing these benefits. The Euglena International Network (EIN) (https://euglenanetwork.org/) aims address challenges, is seeking formative phase support funding.Body startOf nearly 1000 known species euglenoids (Triemer Zakryś, 2015), including gracilis Rhabdomonas...
Abstract Motivation The quality of reference genomes critically affects analyses next generation sequencing experiments. During the construction genome, contigs are organized into their underlying chromosomes in scaffolding step. Historically, software has been difficult to evaluate a systematic and quantitative fashion. To this end, we identified genomic edit distance as compelling method for evaluating scaffold. Results We present Edison, Python implementation Double Cut Join (DCJ)...