A5012479419- HIV Research and Treatment
- HIV-related health complications and treatments
- HIV/AIDS Research and Interventions
- Cytomegalovirus and herpesvirus research
- Metabolomics and Mass Spectrometry Studies
- HIV/AIDS drug development and treatment
- T-cell and B-cell Immunology
- Mosquito-borne diseases and control
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Gut microbiota and health
- Bioinformatics and Genomic Networks
- Virus-based gene therapy research
- Infectious Encephalopathies and Encephalitis
- Cancer Cells and Metastasis
- Neuroinflammation and Neurodegeneration Mechanisms
- Tryptophan and brain disorders
- T-cell and Retrovirus Studies
- Xenotransplantation and immune response
- Animal Disease Management and Epidemiology
- Vector-Borne Animal Diseases
- Genomics and Phylogenetic Studies
- Transplantation: Methods and Outcomes
- Cell Image Analysis Techniques
- Vitamin D Research Studies
10X Genomics (United States)
2023-2024
University of California, San Diego
2015-2023
Johns Hopkins University
2021
Cleveland Clinic Lerner College of Medicine
2021
Case Western Reserve University
2021
Brigham and Women's Hospital
2021
Emory University
2021
Johns Hopkins Medicine
2021
Washington University in St. Louis
2021
VA San Diego Healthcare System
2020
Single-cell and spatial technologies that profile gene expression across a whole tissue are revolutionizing the resolution of molecular states in clinical samples. Current commercially available provide transcriptome single-cell, spatial, or targeted situ analysis. Here, we combine these to explore heterogeneity large, FFPE human breast cancer sections. This integrative approach allowed us differences exist between distinct tumor regions identify biomarkers involved progression towards...
BACKGROUND. Understanding HIV dynamics across the human body is important for cure efforts. This goal has been hampered by technical difficulties and challenge of obtaining fresh tissues.
Abstract Single cell and spatial technologies that profile gene expression across a whole tissue are revolutionizing the resolution of molecular states in clinical samples. Commercially available methods characterize either single or currently limited by low sample throughput and/or plexy, lack on-instrument analysis, destruction histological features epitopes during workflow. Here, we analyzed large, serial formalin-fixed, paraffin-embedded (FFPE) human breast cancer sections using novel...
Abstract Colorectal cancer (CRC) is the second-deadliest in world, yet a deeper understanding of spatial patterns gene expression tumor microenvironment (TME) remains elusive. Here, we introduce Visium HD platform (10x Genomics) and use it to investigate human CRC normal adjacent mucosal tissues from formalin fixed paraffin embedded (FFPE) samples. The first assay available on probe-based transcriptomics workflow that was developed enable whole transcriptome single cell scale analysis. We...
ABSTRACT Previous work in our laboratory demonstrated that passive transfer of porcine reproductive and respiratory syndrome virus (PRRSV)-neutralizing antibodies (NA) protected pregnant sows against failure conferred sterilizing immunity offspring. We report here on the dose requirement for protection by with NA young weaned pigs. The presence a 1:8 titer PRRSV-NA serum consistently pigs viremia. Nevertheless, their lungs, tonsils, buffy coat cells, peripheral lymph nodes contained...
Even when antiretroviral therapy (ART) is started early after infection, HIV DNA might persist in the central nervous system (CNS), possibly contributing to inflammation, brain damage and neurocognitive impairment. Paired blood cerebrospinal fluid (CSF) were collected from 16 HIV-infected individuals on suppressive ART: 9 participants ART <4 months of estimated date infection (EDI) ("early ART"), 7 >14 EDI ("late ART"). For each participant, functioning was measured by Global Deficit Score...
ABSTRACT Asymptomatic replication of human herpesviruses (HHV) is frequent in HIV-infected men and associated with increased T-cell activation HIV disease progression. We hypothesized that the presence cytomegalovirus (CMV) Epstein-Barr virus (EBV) (the most frequently detected HHV) might influence DNA decay during antiretroviral therapy (ART). investigated 607 peripheral blood mononuclear cell (PBMC) samples from 107 CMV-seropositive, who have sex men, started ART within a median 3 months...
To design effective eradication strategies, it may be necessary to target HIV reservoirs in anatomic compartments other than blood. This study examined RNA rebound following interruption of antiretroviral therapy (ART) blood and cerebrospinal fluid (CSF) determine whether the central nervous system (CNS) might serve as an independent source resurgent viral replication. Paired CSF samples were collected longitudinally from 14 chronically HIV-infected individuals undergoing ART interruption....
HIV reservoirs persist in anatomic compartments despite antiretroviral therapy (ART). Characterizing archival DNA the central nervous system (CNS) and other tissues is crucial to inform cure strategies. We evaluated paired autopsy brain-frontal cortex (FC), occipital (OCC), basal ganglia (BG)-and peripheral lymphoid from 63 people with HIV. Participants passed away while virally suppressed on ART at last visit without evidence of CNS opportunistic disease. quantified total all participants...
Abstract We investigated the associations between methamphetamine (meth) use, immune function and dynamics of HIV cytomegalovirus [CMV] in blood genital tract HIV-infected ART-suppressed subjects. Self-reported meth use was associated with increased CD4 + CD8 T-cell proliferation (Ki67 , p < 0.005), activation (CD45RA – CD38 = 0.005) exhaustion (PD-1 0.0004) blood, compared to non-meth users. Meth also a trend towards higher DNA levels ( 0.09) more frequent shedding CMV seminal plasma (p...
Background: The extent of gut microbial translocation, which plays roles in HIV disease progression and non-AIDS comorbidities, appears to vary with the composition microbiome, particularly presence Lactobacillales, reduce mucosal injury. While low proportions Lactobacillales distal microbiome are a very promising indicator measurement is expensive complicated not feasible for clinical routine. (1→3)-β-D-Glucan (BDG) component most fungal cell walls might be surrogate marker proportion...
A low CD4/CD8 ratio in human immunodeficiency virus (HIV)–infected individuals is associated with inflammation and higher risk of non-AIDS morbidity mortality. In this study, we investigated the effect subclinical cytomegalovirus (CMV) Epstein-Barr (EBV) replication on CD4+ CD8+ T-cell dynamics when antiretroviral therapy (ART) started during early infection. We 604 peripheral blood mononuclear cell samples from 108 CMV- EBV-seropositive HIV-infected men who have sex men, ART within a median...
Long-read next-generation amplicon sequencing shows promise for studying complete genes or genomes from complex and diverse populations. Current long-read technologies have challenging error profiles, hindering data processing incorporation into downstream analyses. Here we consider the problem of how to reconstruct, free error, true sequence variants their associated frequencies PacBio reads. Called 'amplicon denoising', this has been extensively studied short-read technologies, but current...
Microbial translocation from the gut is associated with immune dysfunction, persistent inflammation, and likely plays a role in pathogenesis of neurocognitive dysfunction during HIV infection. (1→3)-β-D-Glucan (BDG) component most fungal cell walls might be useful indicator mucosal barrier impairment. The objective this study was to evaluate whether higher blood BDG levels correlate impaired functioning cohort HIV-infected adults suppressed RNA plasma. In cross-sectional study, we measured...
Zika virus (ZIKV), which is associated with microcephaly in infants and Guillain-Barré syndrome, reemerged as a serious public health threat Latin America recent years. Previous high-throughput screening (HTS) campaigns have revealed several potential hit molecules against ZIKV, including methotrexate (MTX), clinically used an anti-cancer chemotherapy anti-rheumatoid agent. We studied the mechanism of action MTX ZIKV relation to its inhibition dihydrofolate reductase (DHFR) vitro using Vero...
Salvador (BA, Brazil) is an endemic area for human T-cell lymphotrophic virus type 1 (HTLV-1). The overall prevalence of HTLV-1 infection in the general population has been estimated to be 1.76%. carriers may develop a variety diseases such as adult leukemia/lymphoma, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis associated with (IDH). IDH chronic severe form childhood exudative involving mainly scalp, neck ears. It recently observed that 30%...
Cytomegalovirus (CMV) has been linked to higher risk of cardiovascular disease and mortality. We aimed determine if CMV is associated with neurocognitive performance in adults infected human immunodeficiency virus (HIV).In this cross-sectional analysis, anti-CMV immunoglobulin G (IgG) concentrations blood DNA copies cerebrospinal fluid (CSF) were measured stored specimens 80 HIV-infected who previously assessed a comprehensive test battery. Thirty-eight taking suppressive antiretroviral...
Background Measurement of HIV DNA-bearing cells in cerebrospinal fluid (CSF) is challenging because few are present. We present a novel application the sensitive droplet digital (dd)PCR this context. Methods analyzed CSF cell pellets and paired peripheral blood mononuclear (PBMC) from 28 subjects, 19 whom had undetectable RNA (<48 copies/mL) both compartments. extracted DNA PBMC using silica-based columns used direct lysis on cells. host housekeeping gene (RPP30) were measured by (dd)PCR....