A5018681389- Mosquito-borne diseases and control
- SARS-CoV-2 and COVID-19 Research
- Computational Drug Discovery Methods
- Mycobacterium research and diagnosis
- COVID-19 Clinical Research Studies
- Cytomegalovirus and herpesvirus research
- Viral Infections and Vectors
- Infectious Diseases and Tuberculosis
- Viral Infections and Immunology Research
- Respiratory viral infections research
- RNA regulation and disease
- Leprosy Research and Treatment
- Parasites and Host Interactions
- SARS-CoV-2 detection and testing
- RNA Research and Splicing
- Ocular Diseases and Behçet’s Syndrome
- Immune Cell Function and Interaction
- Molecular Communication and Nanonetworks
- Virology and Viral Diseases
- Cerebrovascular and genetic disorders
- Advanced Biosensing Techniques and Applications
- Neurogenetic and Muscular Disorders Research
- Bacterial Infections and Vaccines
- interferon and immune responses
- Neurological diseases and metabolism
University of California, San Francisco
2001-2025
Gladstone Institutes
2018-2024
Emory University
2014-2023
Quantitative BioSciences
2020
University of California System
2018
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the cell receptor angiotensin-converting enzyme (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt ACE2. Cryo-electron microscopy (cryo-EM) revealed one nanobody, Nb6, binds in fully inactive conformation with binding domains locked into their inaccessible down state, incapable...
Zika virus (ZIKV) is a significant global health threat, as infection has been linked to serious neurological complications, including microcephaly. Using human stem cell-derived neural progenitor model system, we find that critical cellular quality control process called the nonsense-mediated mRNA decay (NMD) pathway disrupted during ZIKV infection. Importantly, disruption of NMD known cause microcephaly and other disorders. We further identify an interaction between capsid protein...
ABSTRACT Without an effective prophylactic solution, infections from SARS-CoV-2 continue to rise worldwide with devastating health and economic costs. gains entry into host cells via interaction between its Spike protein the cell receptor angiotensin converting enzyme 2 (ACE2). Disruption of this confers potent neutralization viral entry, providing avenue for vaccine design therapeutic antibodies. Here, we develop single-domain antibodies (nanobodies) that potently disrupt ACE2. By screening...
Abstract The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to differential gene expression signatures derived from publicly available data. utilized three independent published studies acquire or generate lists of differentially expressed genes between control SARS-CoV-2-infected samples. Using rank-based pattern matching strategy based on the Kolmogorov–Smirnov Statistic, were queried against profiles...
Powassan virus is a rare but increasingly recognized cause of severe neurological disease.To highlight the diagnostic challenges and neuropathological findings in fatal case encephalitis caused by deer tick (lineage II) patient with follicular lymphoma receiving rituximab, nonspecific anti-GAD65 antibodies, who was initially seen fever orchiepididymitis.Comparison clinical, radiological, histological, laboratory findings, including immunohistochemistry, real-time polymerase chain reaction,...
Abstract As SARS-CoV-2 continues to spread worldwide, tractable primary airway cell models that recapitulate the cell-intrinsic response arising viral variants are needed. Here we describe an adult stem cell-derived human organoid model overexpressing ACE2 receptor (ACE2-OE) supports robust replication while maintaining 3D architecture and cellular diversity of epithelium. ACE2-OE organoids were infected with subjected single-cell RNA-sequencing. Interferon-lambda was upregulated in cells...
Abstract Background. Hansen's disease (HD), or leprosy, is uncommon in the United States. We sought to describe characteristics of patients with HD a US clinic, including an assessment delays diagnosis and reactions, which have both been associated nerve damage. Methods. A retrospective chart review was conducted on seen at clinic southern States between January 1, 2002 31, 2014. Demographic clinical were summarized, diagnosis, frequency other complications peripheral neuropathy. Results....
A major goal in the search for new anti-malarial compounds is to identify mechanisms of action or molecular targets. While cell-based, growth inhibition-based screening have enjoyed tremendous success, an alternative approach specifically assay a given pathway essential cellular process. Here, this work describes development plate-based, vitro luciferase probe inhibitors specific protein synthesis Plasmodium falciparum through use translation system derived from parasite. Using Medicines...
Abstract Background Persons with HIV-associated meningitis are at increased risk of visual impairment. It is often unclear whether this due to the underlying pathophysiology or a second etiology may be present, difficulty in accessing expert exams resource-limited settings. Our long-term goal determine retinal disease prevalence, particularly treatable infections (e.g. CMV retinitis), those meningitis. Here we present pilot feasibility data non-mydriatic fundus imaging sick inpatient...
<h3>Objective</h3> In 2016, Catalonia experienced a pediatric brainstem encephalitis outbreak caused by enterovirus A71 (EV-A71). Conventional testing identified EV in the periphery but rarely CSF. Metagenomic next-generation sequencing (mNGS) and CSF pan-viral serology (VirScan) were deployed to enhance viral detection characterization. <h3>Methods</h3> RNA was extracted from (n = 20), plasma 9), stool 15), nasopharyngeal samples 16) 10 children with meningitis or encephalitis. Pathogens...
Author(s): Crawford, Emily D; Acosta, Irene; Ahyong, Vida; Anderson, Erika C; Arevalo, Shaun; Asarnow, Daniel; Axelrod, Shannon; Ayscue, Patrick; Azimi, Camillia S; Azumaya, Caleigh M; Bachl, Stefanie; Bachmutsky, Iris; Bhaduri, Aparna; Brown, Jeremy Bancroft; Batson, Joshua; Behnert, Astrid; Boileau, Ryan Bollam, Saumya R; Bonny, Alain Booth, David; Borja, Michael Jerico B; Buie, Bryan; Burnett, Cassandra E; Byrnes, Lauren Cabral, Katelyn A; Cabrera, Joana P; Caldera, Saharai; Canales,...
Schistosomiasis is a globally prevalent, debilitating disease that poorly controlled by chemotherapy and for which no vaccine exists. While partial resistance in people may develop over time with repeated infections treatments, some animals, including the brown rat (Rattus norvegicus), are only semi-permissive have natural protection. To understand basis of this protection, we explored nature immune response to infection Schistosoma mansoni. Infection leads production IgG parasite...
We aimed to identify the contribution of central nervous system (CNS) viral coinfection illness in African children with retinopathy-negative or retinopathy-positive cerebral malaria (CM). collected cerebrospinal fluid (CSF) from 272 CM and selected CSF 111 these (38 retinopathy positive, 71 negative, 2 unknown) for analysis by metagenomic next-generation sequencing. found coinfections 7/38 (18.4%) 18/71 (25.4%) children. Excluding HIV-1, human herpesviruses (HHV) represented 61% viruses...
Zika virus (ZIKV) infects fetal neural progenitor cells (NPCs) causing severe neurodevelopmental disorders in utero . Multiple pathways involved normal brain development are dysfunctional infected NPCs but how ZIKV centrally reprograms these remains unknown. Here we show that infection disrupts subcellular partitioning of host transcripts critical for neurodevelopment and functionally link this process to the up-frameshift protein 1 (UPF1). UPF1 is an RNA-binding known regulate decay...
Lipid droplets (LDs) are organelles involved in lipid storage, maintenance of energy homeostasis, protein sequestration, signaling events and inter-organelle interactions. Recently, LDs have been shown to favor the replication members from different viral families, such as Flaviviridae Coronaviridae. In this work, we found that essential for Arenaviridae family. A virus-driven reduction number was observed cultures infected with Junín mammarenavirus (JUNV), caused part by action...
In non-endemic countries, leprosy, or Hansen's disease (HD), remains rare and is often underrecognized. Consequently, the literature currently lacking in clinical descriptions of leprosy complications United States. Immune-mediated inflammatory states known as reactions are common HD. Type 1 typical borderline cases occur 30% patients present swelling inflammation existing skin lesions, neuritis, nerve dysfunction. 2 systemic events that at lepromatous end spectrum, symptoms include fever,...
Covalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-2 have great potential as antivirals, but their non-specific reactivity with thiols has limited development. In this report, we performed an 8000 molecule electrophile screen against PLpro and identified α-chloro amide fragment, termed compound 1, which inhibited replication in cells, also had low thiols. Compound 1 covalently reacts active site cysteine PLpro, IC50 18 μM for inhibition. reacted glutathione 1-2 orders...
Abstract The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to differential gene expression signatures derived from publicly available data. utilized three independent published studies acquire or generate lists of differentially expressed genes between control SARS-CoV-2-infected samples. Using rank-based pattern matching strategy based on the Kolmogorov-Smirnov Statistic, were queried against profiles...
Abstract As SARS-CoV-2 continues to spread worldwide, tractable primary airway cell models that accurately recapitulate the cell-intrinsic response arising viral variants are needed. Here we describe an adult stem cell-derived human organoid model overexpressing ACE2 receptor supports robust replication while maintaining 3D architecture and cellular diversity of epithelium. ACE2-OE organoids were infected with subjected single-cell RNA-sequencing. NF-κB inhibitor alpha was consistently...
Abstract Zika virus (ZIKV) is a mosquito-borne RNA that can infect fetuses in utero causing characteristic neurodevelopmental disorders including microcephaly. We previously showed ZIKV infection downregulates expression of up-frameshift protein 1 (UPF1), helicase/ATPase and central regulator the nonsense-mediated mRNA decay pathway. Here, we identify novel function nuclear UPF1 export. Using crosslinking immunoprecipitation followed by sequencing associated transcripts as well fluorescence...
To assess the utility of glial antibody testing and metagenomic next-generation sequencing (mNGS) serum cerebrospinal fluid (CSF) in diagnostic work-up myelopathy Ugandan patients.