A5058260819- HIV Research and Treatment
- Virus-based gene therapy research
- Cellular transport and secretion
- SARS-CoV-2 and COVID-19 Research
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Monoclonal and Polyclonal Antibodies Research
- COVID-19 Clinical Research Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Virology and Viral Diseases
- Mosquito-borne diseases and control
- HIV/AIDS drug development and treatment
- Legionella and Acanthamoeba research
- Vibrio bacteria research studies
- vaccines and immunoinformatics approaches
- Traditional and Medicinal Uses of Annonaceae
- Glycosylation and Glycoproteins Research
- Molecular Biology Techniques and Applications
- Infectious Encephalopathies and Encephalitis
- interferon and immune responses
- Ubiquitin and proteasome pathways
- Bacteriophages and microbial interactions
- Influenza Virus Research Studies
- Bacterial Genetics and Biotechnology
- Toxoplasma gondii Research Studies
VA San Diego Healthcare System
2015-2023
University of California, San Diego
2017-2023
Veterans Medical Research Foundation of San Diego
2021-2022
Center for Global Health
2021
Imperial College London
2009-2019
MRC Laboratory for Molecular Cell Biology
2013
Hammersmith Hospital
2012
University Medical Center Hamburg-Eppendorf
2009
Universität Hamburg
2009
John Radcliffe Hospital
2008-2009
SARS-CoV-2 is the novel coronavirus that causative agent of COVID-19, a sometimes-lethal respiratory infection responsible for world-wide pandemic. The envelope (E) protein, one four structural proteins encoded in viral genome, 75-residue integral membrane protein whose transmembrane domain exhibits ion channel activity and cytoplasmic participates protein-protein interactions. These activities contribute to several aspects replication-cycle, including virion assembly, budding, release,...
Adeno-associated virus/phage (AAVP) is a gene delivery vector constructed as hybrid between adeno-associated virus and filamentous phage. Tumor targeting following systemic administration has previously been demonstrated in several vivo cancer models, with tumor specificity achieved through display of an α(v) integrin-targeting ligand on the capsid. However, high titers AAVP are required for transduction large numbers mammalian cells. This study first to investigate mechanisms involved entry...
Significance Over the past decade, we have used adeno-associated virus phage (AAVP) vectors for discovery, preclinical imaging, and translation therapy. However, hurdles remained with AAVP-mediated transgene delivery: both preinternalization (nonspecific protein adsorption, resulting in antibody-based neutralization) postinternalization (endolysosomal degradation). As a proof-of-concept, designed, developed, validated next-generation of targeted AAVP that mitigate these obstacles to...
Abstract Suicide gene transfer is the most commonly used cytotoxic approach in cancer therapy; however, a successful suicide therapy depends on generation of efficient targeted systemic delivery vectors. We recently reported that selective genes such as herpes simplex virus thymidine kinase (HSVtk) to tumor endothelial cells through novel adeno-associated virus/phage vector leads suppression growth. This marked effect has been postulated result primarily from death by hypoxia following...
Legionella pneumophila is an intracellular bacterium that resides within amoebae and macrophages in a specialized compartment termed the Legionella-containing vacuole (LCV). As well as providing niche for replication, LCV helps to prevent release of bacterial components into cytoplasm. Recognition these danger signals by host activates immune responses leading clearance bacterium. Here, we examined role two important virulence factors L. pneumophila, potent signal flagellin translocated...
Legionella pneumophila, the causative agent of Legionnaires' disease, uses Dot/Icm type IV secretion system (T4SS) to translocate more than 300 effectors into host cells, where they subvert cell signaling. The function and targets most remain unknown. PieE is a 69-kDa effector containing three coiled-coil (CC) regions 2 transmembrane (TM) helices followed by fourth CC region. Here, we report that dimerized an interaction between CC3 CC4. We found ectopically expressed localized endoplasmic...
SUMMARY A deficient interferon response to SARS-CoV-2 infection has been implicated as a determinant of severe COVID-19. To identify the molecular effectors that govern control infection, we conducted large-scale gain-of-function analysis evaluated impact human stimulated genes (ISGs) on viral replication. limited subset ISGs were found including endosomal factors inhibited entry, nucleic acid binding proteins suppressed RNA synthesis, and highly enriched cluster ER Golgi-resident...
Bacteriophage (phage), which are viruses that infect bacteria only, have shown promise as vehicles for targeted cancer gene therapy, albeit with poor efficiency. Recently, we generated an improved version of phage vectors by incorporating cis genetic elements adeno-associated virus (AAV). This novel AAV/phage hybrid (AAVP) efficiently delivered systemically administered therapeutic genes to various tumor targets displaying integrin tumor-targeting ligand on the capsid. However, inherent...
Cellular membrane proteins in the SERINC family, especially SERINC5, inhibit infectivity of retroviral virions. This inhibition is counteracted by proteins, specifically, HIV-1 Nef, MLV glycoGag, and EIAV S2. One consequence such a host-pathogen “arms race” compensatory change host antiviral protein as it evolves to escape effects viral antagonists. often reflected genetic signature, positive selection, which conspicuously missing SERINC5 . Here we show that despite this lack evidence,...
HIV-1 Vpu decreases the exposure of epitopes within viral envelope glycoprotein (Env) on surface infected cells by downregulating both BST2 and CD4. To test hypothesis that inhibiting activity would increase these sensitize to antibody-dependent cellular cytotoxicity (ADCC), we treated with Nedd8 activation enzyme (NAE) inhibitor MLN4924, which inhibits cullin1-based ubiquitin ligase complex coopted degrade targets. Treatment HeLa MLN4924 or expression a dominant negative mutant cullin1...
Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC/EHEC) manipulate many cell processes by injecting effector proteins from the bacteria into host via a Type III secretion system. In this paper we report that protein EspG disrupts recycling endosome function. particular, found following transferrin binding endocytosis reduces of receptor (TfR), prototypical protein, an intracellular location to surface, resulting in accumulation TfR within cell. The surface levels three receptors...
HIV ‐1 Vpu modulates cellular transmembrane proteins to optimize viral replication and provide immune‐evasion, triggering ubiquitin‐mediated degradation of some targets but also modulating endosomal trafficking deplete them from the plasma membrane. Interactions between heterotetrameric clathrin adaptor protein (AP) complexes AP‐1 AP ‐2 have been described, yet molecular basis functional roles such interactions are incompletely defined. To investigate signals encoded by Vpu, we fused...
A deficient interferon response to SARS-CoV-2 infection has been implicated as a determinant of severe COVID-19. To identify the molecular effectors that govern control infection, we conducted large-scale gain-of-function analysis evaluated impact human stimulated genes (ISGs) on viral replication. limited subset ISGs were found including endosomal factors inhibited entry, nucleic acid binding proteins suppressed RNA synthesis, and highly enriched cluster ER Golgi-resident translation...
As systems biology approaches to virology have become more tractable, highly studied viruses such as HIV can now be analyzed in new unbiased ways, including spatial proteomics. We employed here a differential centrifugation protocol fractionate Jurkat T cells for proteomic analysis by mass spectrometry; these contain inducible HIV-1 genomes, enabling us look changes the proteome induced viral gene expression. Using proteomics data, we evaluated merits of several reported machine learning...
Abstract SARS-CoV-2 is the novel coronavirus that causative agent of COVID-19, a sometimes-lethal respiratory infection responsible for world-wide pandemic. The envelope (E) protein, one four structural proteins encoded in viral genome, 75-residue integral membrane protein whose transmembrane domain exhibits ion channel activity and cytoplasmic participates protein-protein interactions. These activities contribute to several aspects replication-cycle, including virion assembly, budding,...
The HIV-1 protein Nef suppresses multiple immune surveillance mechanisms to promote viral pathogenesis 1 . Individuals infected with encoding defective nef genes do not develop AIDS for decades 2,3 A key target of is the cellular receptor CD4. Although essential entry into host cells, CD4 problematic virus later in its replication cycle: disrupts processing glycoprotein, Env, inhibiting infectivity 4 ; it interferes release new virions 5,6 and causes vulnerability superinfection, causing...
The host transmembrane protein SERINC5 is incorporated into retrovirus particles and inhibits HIV-1 infectivity. lentiviral Nef counteracts by downregulating it from the cell surface preventing its incorporation virions. ability of to antagonize factor varies in magnitude between different isolates. After having identified a subtype H nef allele unable promote infectivity presence SERINC5, we investigated molecular determinants responsible for defective counteraction factor. Chimeric...