A5049620926- Hepatitis C virus research
- Hepatitis B Virus Studies
- SARS-CoV-2 and COVID-19 Research
- Mosquito-borne diseases and control
- Liver Disease Diagnosis and Treatment
- COVID-19 Clinical Research Studies
- Cellular transport and secretion
- HIV Research and Treatment
- Viral gastroenteritis research and epidemiology
- CRISPR and Genetic Engineering
- interferon and immune responses
- Endoplasmic Reticulum Stress and Disease
- Viral Infections and Vectors
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Economic Policies and Impacts
- Cancer Immunotherapy and Biomarkers
- Economic Theory and Institutions
- Viral Infectious Diseases and Gene Expression in Insects
- Viral Infections and Outbreaks Research
- Economic theories and models
- Innovations in Medical Education
- Insect symbiosis and bacterial influences
- Systemic Lupus Erythematosus Research
- Capital Investment and Risk Analysis
University of Michigan
2016-2025
VA Ann Arbor Healthcare System
2014-2024
Michigan Medicine
2011-2023
Michigan United
2011-2022
Women's and Children's Hospital
2012-2022
The University of Adelaide
2010-2022
University of California, Berkeley
2018
National Bureau of Economic Research
2018
University of the Basque Country
2018
Università della Svizzera italiana
2018
The interaction of cytoplasmic dynein with its cargoes is thought to be indirectly mediated by dynactin, a complex that binds the intermediate chain. However, roles other subunits in cargo binding have been unknown. Here we demonstrate translocates rhodopsin-bearing vesicles along microtubules. This occurs directly between C-terminal tail rhodopsin and Tctex-1, light mutations responsible for retinitis pigmentosa inhibit this interaction. Our results point an alternative docking mechanism...
The cGAS-STING pathway plays a crucial role in innate immune activation against cancer and infections, STING agonists based on cyclic dinucleotides (CDN) have garnered attention for their potential use immunotherapy vaccines. However, the limited drug-like properties of CDN necessitate an efficient delivery system to system. To address these challenges, we developed immunostimulatory agonists. Here, examined aqueous coordination interactions between metal ions report that mixed with Zn2+...
Hepatitis C virus (HCV) is a single-stranded RNA that replicates on endoplasmic reticulum-derived membranes. HCV particle assembly dependent the association of core protein with cellular lipid droplets (LDs). However, it remains uncertain whether occurs at LD membrane itself or closely associated ER Furthermore, not known how replication complex and progeny genomes physically associate presumed sites virion near LDs. Using an unbiased proteomic strategy, we have found Rab18 interacts...
Although flaviviruses co-opt the function of host endoplasmic reticulum (ER) membrane protein complex (EMC) during infection, a mechanistic explanation for this observation remains unclear. Here, we show that EMC promotes biogenesis dengue virus (DENV) and Zika (ZIKV) non-structural multi-pass transmembrane proteins NS4A NS4B, which are necessary viral replication. The binds to NS4B colocalizes with DENV replication organelle. Mapping analysis reveals two N-terminal marginally hydrophobic...
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiologic agent for global COVID-19 pandemic, triggers formation of endoplasmic reticulum (ER)-derived replication organelles, including double-membrane vesicles (DMVs), in host cell to support viral replication. Here, we clarify how SARS-CoV-2 hijacks factors construct DMVs. We show that ER morphogenic proteins reticulon-3 (RTN3) and RTN4 help drive DMV formation, enabling replication, which leads productive infection....
Natural products provide a vast array of chemical structures to explore in the discovery new medicines. Although secondary metabolites produced by microbes have been developed treat variety diseases, including bacterial and fungal infections, date there has limited investigation natural with antiviral activity. In this report, we used phenotypic cell-based replicon assay coupled an iterative biochemical fractionation process identify, purify, characterize compounds marine microbes. We...
Background Hepatitis C virus (HCV), like other positive-sense RNA viruses, replicates on an altered host membrane compartment that has been called the "membranous web." The mechanisms by which membranous web are formed from cellular membranes poorly understood. Several recent interference screens have demonstrated a critical role for phosphatidylinositol 4-kinase PI4KA in HCV replication. We sought to define function of viral Methodology/Principal Findings Using nonreplicative model...
Medical school assessments should foster the development of higher-order thinking skills to support clinical reasoning and a solid foundation knowledge. Multiple-choice questions (MCQs) are commonly used assess student learning, well-written MCQs can learner engagement in higher levels cognitive such as application or synthesis Bloom's taxonomy has been identify that students' critical skills, with evidence suggesting deeper conceptual understanding scientific process skills. Similarly,...
Dengue virus (DENV) is the most common arboviral infection globally, infecting an estimated 390 million people each year. We employed a genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screen to identify host dependency factors required for DENV propagation and identified oligosaccharyltransferase (OST) complex as essential factor infection. Mammalian cells express two OSTs containing either STT3A or STT3B. found that canonical catalytic function of...
Abstract There are no approved therapies for Ebola virus infection. Here, to find potential therapeutic targets, we perform a screen genes essential (EBOV) We identify GNPTAB , which encodes the α and β subunits of N-acetylglucosamine-1-phosphate transferase. show that EBOV infection knockout cell line is impaired, this reversed by reconstituting expression. Fibroblasts from patients with mucolipidosis II, disorder associated mutations in refractory EBOV, whereas cells their healthy parents...
Small-molecule targeting of RNA stem loops in 5′-end SARS-CoV-2 reveals novel targets for viral inhibition.
Despite the existence of multiple subunit isoforms for microtubule motor cytoplasmic dynein, it has not yet been directly shown that dynein complexes with different compositions exhibit properties. The 14-kD light chain Tctex-1, but its homologue RP3, binds to rhodopsin's COOH-terminal tail, which encodes an apical targeting determinant in polarized epithelial Madin-Darby canine kidney (MDCK) cells. We demonstrate Tctex-1 and RP3 compete binding intermediate overexpressed displaces...
ABSTRACT Although the mechanisms of action (MoA) nonstructural protein 3 inhibitors (NS3i) and NS5B (NS5Bi) are well understood, MoA cyclophilin (CypI) NS5A (NS5Ai) not fully defined. In this study, we examined whether CypI NS5Ai interfere with hepatitis C virus (HCV) RNA synthesis replication complexes (RCs) or an earlier step HCV replication, creation double-membrane vesicles (DMVs) essential for replication. contrast to NS5Bi, both do block by way RCs, suggesting that they exert their...
Several SARS-CoV-2 vaccines have received EUAs, but many issues remain unresolved, including duration of conferred immunity and breadth cross-protection. Adjuvants that enhance shape adaptive immune responses confer broad protection against variants will be pivotal for long-term as drift continue to emerge. We developed an intranasal, rationally designed adjuvant integrating a nanoemulsion (NE) activates TLRs NLRP3 with RNA agonist RIG-I (IVT DI). The combination spike protein antigen...
Abstract The COVID-19 pandemic is caused by SARS-CoV-2, an enveloped RNA virus. Despite extensive investigation, the molecular mechanisms for its assembly and secretion remain largely elusive. Here, we show that SARS-CoV-2 infection induces global alterations of host endomembrane system, including dramatic Golgi fragmentation. virions are enriched in fragmented Golgi. Disrupting function with small molecules strongly inhibits viral infection. Significantly, down-regulates GRASP55 but...