A5056329623- HIV Research and Treatment
- Bacteriophages and microbial interactions
- HIV/AIDS Research and Interventions
- HIV/AIDS drug development and treatment
- interferon and immune responses
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Vibrio bacteria research studies
- Bacterial Genetics and Biotechnology
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- Endoplasmic Reticulum Stress and Disease
- Gut microbiota and health
- Viral Infections and Vectors
- Immune cells in cancer
- LGBTQ Health, Identity, and Policy
- Evolution and Genetic Dynamics
- Immunodeficiency and Autoimmune Disorders
- Genomics and Phylogenetic Studies
University of California, San Francisco
2022-2024
University of California System
2023
National Institute of Allergy and Infectious Diseases
2018-2021
National Institutes of Health
2018-2021
Center for Cancer Research
2020
A fundamental strategy of eukaryotic antiviral immunity involves the cGAS enzyme, which synthesizes 2′,3′-cGAMP and activates effector STING. Diverse bacteria contain cGAS-like enzymes that produce cyclic oligonucleotides induce anti-phage activity, known as CBASS. However, this activity has only been demonstrated through heterologous expression. Whether harboring CBASS antagonize co-evolve with phages is unknown. Here, we identified an endogenous enzyme in Pseudomonas aeruginosa generates...
Therapeutic strategies aimed at achieving antiretroviral therapy (ART)-free HIV remission in infected individuals are under active investigation. Considering the vast majority of HIV-infected experience plasma viral rebound upon cessation therapy, clinical trials evaluating efficacy curative would likely require inclusion ART interruption. However, it is unclear what impact short-term analytical treatment interruption (ATI) and subsequent reinitiation have on immunologic virologic parameters...
Bacteria use a diverse arsenal of anti-phage immune systems, including CRISPR-Cas and restriction enzymes. Recent advances in system discovery annotation tools have unearthed many unique often encoded horizontally transferred defense islands, which can be transferred. Here, we developed Hidden Markov Models (HMMs) for systems queried microbial genomes on the NCBI database. Out 30 species with >200 completely sequenced genomes, our analysis found Pseudomonas aeruginosa exhibits greatest...
Abstract Feminizing hormone therapy (FHT) may interact with human immunodeficiency virus preexposure prophylaxis (PrEP). We found that transgender women who took FHT exhibited a 7-fold lower rectal tissue ratio of PrEP’s active metabolites vs competing deoxynucleotides compared to cisgender and men (P = .03) inversely correlated estradiol (ρ –0.79; P < .05). Thus, negatively impact PrEP efficacy. Clinical Trials Registration . NCT02983110.
Despite the substantial clinical benefits of antiretroviral therapy (ART), complete eradication HIV has not been possible. The gastrointestinal tract and associated lymphoid tissues may play an important role in pathogenesis infection. integrin α4β7 facilitates homing T lymphocytes to gut by binding mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expressed on venules gut-associated tissue. CD4+ cells with increased expression are susceptible infection be key players subsequent virus...
Historical data regarding time to viral rebound following analytical treatment interruption (ATI) have been used determine therapeutic efficacy in HIV cure trials; however, such were collected from studies conducted a decade or more ago and included participants receiving older antiretroviral therapy (ART) regimens with infrequent virologic monitoring. We study of 22 HIV-infected modern ART the kinetics plasma ATI. Our suggest that does not alter when compared previous immunologic...
Summary The recently discovered c yclic-oligonucleotide- b ased a nti-phage s ignaling ystem (CBASS) is related to eukaryotic cGAS-STING anti-viral immunity and present in diverse prokaryotes. However, our understanding of how CBASS detects, inhibits, co-evolves with phages limited because function has only been studied reconstituted heterologous systems. Here, we identify phage-encoded antagonist ( acbIIA1, nti- cb ass type II-A gene 1 ) necessary for phage replication the presence...
The co-evolution of prokaryotes, phages, and mobile genetic elements (MGEs) over the past billions years has driven emergence diversification defense anti-defense systems alike. Anti-defense proteins have diverse functional domains, sequences, are typically small, creating a challenge to detect homologs across prokaryotic genomes. To date, no tools comprehensively annotate within desired genome or MGE. Here, we developed "AntiDefenseFinder" - free open-source tool web service that detects...
Abstract The co-evolution of prokaryotes, phages and mobile genetic elements (MGEs) has driven the diversification defense anti-defense systems alike. Anti-defense proteins have diverse functional domains, sequences are typically small, creating a challenge to detect homologs across prokaryotic phage genomes. To date, no tools comprehensively annotate within desired sequence. Here, we developed ‘AntiDefenseFinder’—a free open-source tool web service that detects 156 one or more in any...
Abstract Persistent exposure to antigen leads T-cell exhaustion and immunologic dysfunction. We examined the immune markers T cell immunoglobulin ITIM domain (TIGIT) programmed death protein 1 (PD-1) in human immunodeficiency virus (HIV)–infected healthy individuals relationship with cytotoxic CD8+ T-lymphocyte activity. Frequencies of TIGIT but not PD-1 were positively correlated activity HIV-aviremic individuals; however, there was no correlation HIV-viremic individuals. Transcriptome...
Prokaryotic anti-phage immune systems use TIR (toll/interleukin-1 receptor) and cGAS (cyclic GMP-AMP synthase) enzymes to produce 1"-3'/1"-2' glycocyclic ADPR (gcADPR) cyclid di-/trinucleotides (CDNs CTNs) signaling molecules that limit phage replication, respectively
Therapeutic strategies for achieving sustained virologic remission are being explored in human immunodeficiency virus (HIV)-infected individuals who began antiretroviral therapy (ART) during the early phase of infection. In evaluation such therapies, clinical protocols should include analytical treatment interruption (ATI); however, immunologic and impact ATI initiated ART has not been fully delineated. We demonstrate that causes neither expansion HIV reservoirs nor abnormalities following...
A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission virus, suppress viral replication, delay plasma rebound following discontinuation antiretroviral therapy in animal models infected humans. However, degree extent which such bNAbs interact with primary lymphocytes not fully delineated. Here, we show that certain glycan-dependent bNAbs, as PGT121 PGT151, bind B, activated T,...
An efficacious human immunodeficiency virus (HIV) vaccine will likely require induction of both mucosal and systemic immune responses. We compared the immunogenicity protective efficacy two mucosal/systemic regimens investigated their effects on rectal microbiome. Rhesus macaques were primed twice mucosally with replication-competent adenovirus type 5 host range mutant (Ad5hr)-simian (SIV) recombinants boosted intramuscularly ALVAC-SIV recombinant plus SIV gp120 protein or DNA for genes...
Summary CBASS is a common anti-phage immune system that uses cyclic oligonucleotide signals to activate effectors and limit phage replication. In turn, phages encode anti-CBASS (Acb) proteins. We recently uncovered widespread protein Acb2 acts as “sponge” by forming hexamer complex with three cGAMP molecules. Here, we identified binds sequesters many cGAS-produced dinucleotides in vitro inhibits cGAMP-mediated STING activity human cells. Surprisingly, also trinucleotides 3’3’3’-cyclic...
ABSTRACT Bacteria use a diverse arsenal of anti-phage immune systems, including CRISPR-Cas and restriction enzymes. Identifying the full defense repertoire given species is still challenging, however. Here, we developed computational tool to broadly identify which was applied >180,000 genomes available on NCBI, revealing Pseudomonas aeruginosa possess most any with >200 sequenced genomes. Using network analysis common neighbors surprisingly identified two highly conserved core hotspot...