A5046290704- Cancer Genomics and Diagnostics
- Sarcoma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- RNA Research and Splicing
- Insect symbiosis and bacterial influences
- Cancer Cells and Metastasis
- Pleural and Pulmonary Diseases
- Orthopedic Infections and Treatments
- Cancer Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Mosquito-borne diseases and control
- Entomopathogenic Microorganisms in Pest Control
- Radiation Effects in Electronics
- VLSI and Analog Circuit Testing
- Mitochondrial Function and Pathology
- Environmental DNA in Biodiversity Studies
- Single-cell and spatial transcriptomics
- Dengue and Mosquito Control Research
- Scientific Computing and Data Management
- Malaria Research and Control
- Ubiquitin and proteasome pathways
- CAR-T cell therapy research
Nationwide Children's Hospital
2020-2024
The Ohio State University
2022-2023
Sandia National Laboratories
2023
University of Pittsburgh
2022
Creative Commons
2022
Taylor and Francis (United Kingdom)
2022
University of Maryland, Baltimore
2018-2021
Cleveland Clinic Lerner College of Medicine
2014-2018
Cleveland Clinic
2015-2018
Intuit (United States)
2015
Understanding mosquito host choice is important for assessing vector competence or identifying disease reservoirs. Unfortunately, the availability of an unbiased method comprehensively evaluating composition insect blood meals very limited, as most current molecular assays only test presence a few pre-selected species. These approaches also have limited ability to identify multiple mammalian hosts in single meal. Here, we describe novel high-throughput sequencing that enables analysis 96...
Abstract Analysis of environmental DNA (eDNA) enables the detection species interest from water and soil samples, typically using species-specific PCR. Here, we describe a method to characterize biodiversity given environment by amplifying eDNA primer pairs targeting wide range taxa high-throughput sequencing for identification. We tested this approach on 91 samples 40 mL collected along Cuyahoga River (Ohio, USA). amplified 12 mammals, fish, amphibians, birds, bryophytes, arthropods,...
Plasmodium vivax and P. falciparum, the parasites responsible for most human malaria worldwide, exhibit striking biological differences, which have important clinical consequences. Unfortunately, vivax, unlike cannot be cultivated continuously in vitro, limits our understanding of its biology and, consequently, ability to effectively control malaria. Here, we describe single-cell gene expression profiles 9,215 from bloodstream infections Aotus Saimiri monkeys. Our results show that...
Abstract Background Tumors are complex tissues containing collections of phenotypically diverse malignant and nonmalignant cells. We know little the mechanisms that govern heterogeneity tumor cells nor role plays in overcoming stresses, such as adaptation to different microenvironments. Osteosarcoma is an ideal model for studying these mechanisms—it exhibits widespread inter- intra-tumoral heterogeneity, predictable patterns metastasis, a lack clear targetable driver mutations. Understanding...
ABSTRACT Plasmodium vivax parasites have a unique dormant stage that can cause relapses weeks or months after the initial infection. These are among main challenges of malaria control as they constitute reservoir is difficult to eliminate. Since field studies confounded by reinfections and possible recrudescence drug-resistant parasites, most analyses P. focused on travelers returning from regions endemicity. However, it not clear whether these individuals accurately recapitulate relapse...
Plasmodium vivax resistance to chloroquine (CQ) has been reported worldwide, although the World Health Organization clinical drug efficacy studies protocol does not permit classification of patient outcomes.We enrolled 40 patients with P. malaria in northeastern Cambodia, where >17% treatment failures were previously reported. Patients treated CQ (30 mg/kg) and followed for 2 months, frequent examination capillary blood sample collection microscopy, molecular parasite detection genotyping,...
Osteosarcoma is an aggressive malignancy characterized by high genomic complexity. Identification of few recurrent mutations in protein coding genes suggests that somatic copy-number aberrations (SCNA) are the genetic drivers disease. Models around instability conflict-it unclear whether osteosarcomas result from pervasive ongoing clonal evolution with continuous optimization fitness landscape or early catastrophic event followed stable maintenance abnormal genome. We address this question...
Clinical sequencing efforts are rapidly identifying sarcoma gene fusions that lack functional validation. An example is the fusion of transcriptional coactivators, VGLL2-NCOA2, found in infantile rhabdomyosarcoma. To delineate VGLL2-NCOA2 tumorigenic mechanisms and identify therapeutic vulnerabilities, we implement a cross-species comparative oncology approach with zebrafish, mouse allograft, patient samples. We find sufficient to generate mesenchymal tumors display features immature...
Lung metastasis is responsible for nearly all deaths caused by osteosarcoma, the most common pediatric bone tumor. How malignant cells coerce lung microenvironment to support metastatic growth unclear. The purpose of this study identify metastasis-specific therapeutic vulnerabilities delineating cellular and molecular mechanisms underlying osteosarcoma niche formation.
<p>scRNA-seq marker expression and protein level validation of macrophage epithelial cell enrichment</p>
<p>Niche-wide changes in target signaling pathway activity with immediate and delayed nintedanib</p>
<p>Immediate vs delayed treatment, tumor burden-based randomization</p>
<div>AbstractPurpose:<p>Lung metastasis is responsible for nearly all deaths caused by osteosarcoma, the most common pediatric bone tumor. How malignant cells coerce lung microenvironment to support metastatic growth unclear. The purpose of this study identify metastasis-specific therapeutic vulnerabilities delineating cellular and molecular mechanisms underlying osteosarcoma niche formation.</p>Experimental Design:<p>Using single-cell RNA sequencing, we characterized...
<p>Chronic wound epithelial cells (KRT8+) accumulate in human patient osteosarcoma lung metastasis</p>
<p>Unaffected thick tissue epithelial z-stack</p>
<p>Metastasis thick tissue epithelial z-stack</p>
<p>Tumor cell-intrinsic effects of nintedanib</p>
<p>K7M2 shows evidence of acute alveolar injury during osteosarcoma metastasis</p>
<p>Mechanistic and pharmacodynamic effects of nintedanib</p>
<p>Ligand-Receptor-Target (NicheNET) gene expression analysis</p>
Epidemiological and animal studies have shown that maternal diet can influence metabolism in adult offspring. However, the molecular mechanisms underlying these changes remain poorly understood. Here, we characterize phenotypes induced by obesity a mouse model examine gene expression epigenetic offspring.We analyzed genetically identical male mice born from dams fed high- or low-fat throughout pregnancy until day 21 postpartum. After weaning, half of males each group were high-fat diet,...
γ-Aminobutyrate (GAB), the biochemical form of (GABA) γ-aminobutyric acid, participates in shaping physiological processes, including immune response. How GAB metabolism is controlled to mediate such functions remains elusive. Here we show that one most abundant metabolites CD4
HES3 is a basic helix-loop-helix transcription factor that regulates neural stem cell renewal during development. overexpression predictive of reduced overall survival in patients with fusion-positive rhabdomyosarcoma, pediatric cancer resembles immature and undifferentiated skeletal muscle. However, the mechanisms cooperation rhabdomyosarcoma are unclear likely related to her3/HES3's role neurogenesis. To investigate HES3's function development, we generated zebrafish CRISPR/Cas9 null...
Several of the most devastating human diseases are caused by eukaryotic parasites transmitted arthropod vectors or through food and water contamination. These pathogens only represent a fraction all unicellular eukaryotes helminths that present in environment many uncharacterized organisms might have subtle but pervasive effects on health, including modifying microbiome where they reside. Unfortunately, while we modern molecular tools to characterize bacterial and, lesser extent, fungal...