A5066623545- HIV Research and Treatment
- Immune Cell Function and Interaction
- vaccines and immunoinformatics approaches
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Hepatitis C virus research
- HIV/AIDS drug development and treatment
- Drug-Induced Adverse Reactions
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- HIV/AIDS Research and Interventions
- Immunodeficiency and Autoimmune Disorders
- Genomics and Phylogenetic Studies
- Cytomegalovirus and herpesvirus research
- Bacteriophages and microbial interactions
- Asthma and respiratory diseases
- HIV-related health complications and treatments
- CAR-T cell therapy research
- Hepatitis B Virus Studies
- Helicobacter pylori-related gastroenterology studies
- Molecular Biology Techniques and Applications
- Animal Virus Infections Studies
- SARS-CoV-2 and COVID-19 Research
- Single-cell and spatial transcriptomics
- Respiratory viral infections research
Murdoch University
2016-2025
Vanderbilt University Medical Center
2019-2024
Avenir Health
2023
Vanderbilt University
2019-2023
Carrington College
2022
Itron (France)
2022
Cooley (United States)
2022
University of Saint Mary of the Lake
2022
Walter Eucken Institut
2022
Institute of Infection and Immunity
2016
Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, also those drive progression to chronicity instrumental for understanding pathogenesis vaccine design. A comprehensive longitudinal analysis the population was conducted in four subjects followed from very early acute resolution disease outcome. By means next generation sequencing (NGS) standard cloning/Sanger...
Genetic variations across the SARS-CoV-2 genome may influence transmissibility of virus and host's anti-viral immune response, in turn affecting frequency variants over time. In this study, we examined adjacent amino acid polymorphisms nucleocapsid (R203K/G204R) that arose on background spike D614G change describe how strains harboring these changes became dominant circulating globally.Deep-sequencing data from public databases clinical samples were analyzed to identify map genetic...
Assessing the location and frequency of HIV integration sites in latently infected cells can potentially inform our understanding how persists during combination antiretroviral therapy. We developed a novel high throughput sequencing method to evaluate cell lines determine whether there was virus replication or clonal expansion these observed as multiple events at same position.We modified previously reported using random DNA shearing PCR allow for robotic processing identify site lines....
We have developed periscope, a tool for the detection and quantification of subgenomic RNA (sgRNA) in SARS-CoV-2 genomic sequence data. The translation genome most open reading frames (ORFs) occurs via intermediates termed "subgenomic RNAs." sgRNAs are produced through discontinuous transcription, which relies on homology between transcription regulatory sequences (TRS-B) upstream ORF start codons that TRS-L, is located 5' UTR. TRS-L immediately preceded by leader sequence. This therefore...
Immune checkpoint therapy (ICT) results in durable responses individuals with some cancers, but not all patients respond to treatment. ICT improves CD8+ cytotoxic T lymphocyte (CTL) function, changes tumor antigen-specific CTLs post that correlate successful have been well characterized. Here, we studied murine models dichotomous ICT. We tracked CTL frequencies and phenotype before after responding non-responding animals. Tumor increased within draining lymph nodes ICT, exhibited an effector...
Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) is a rare but life-threatening cutaneous drug reaction mediated by human leukocyte antigen (HLA) class I-restricted CD8
Abstract Select CMV epitopes drive life-long CD8+ T cell memory inflation, but the extent of CD4 inflation is poorly studied. CD4+ cells specific for human (HCMV) are elevated in HIV+ HCMV+ subjects. To determine whether HCMV epitope–specific occurs during HIV infection, we used HLA-DR7 (DRB1*07:01) tetramers loaded with glycoprotein B DYSNTHSTRYV (DYS) epitope to characterize circulating coinfected HLA-DR7+ long-term nonprogressor subjects undetectable plasma viremia. DYS-specific were...
Genes of the human leukocyte antigen (HLA) system encode cell-surface proteins involved in regulation immune responses, and way drugs interact with HLA peptide binding groove is important immunopathogenesis T-cell mediated drug hypersensitivity syndromes. Nevirapine (NVP), an HIV-1 antiretroviral treatment-limiting reactions (HSRs) associated multiple class I II alleles. Here we utilize a novel analytical approach to explore these multi-allelic associations by systematically examining...
Background We aimed to assess the impact of genomic human leukocyte antigen (HLA)-I/II homozygosity on survival benefit patients with unresectable locally advanced, metastatic non-small lung cancer treated by single-agent programmed cell death protein-1/programmed ligand 1 (PD1/PDL1) inhibitors. Methods collected blood from 170 advanced immunotherapy at two major oncology centers in Western Australia. Genomic DNA was extracted white cells and used for HLA-I/II high-resolution typing. tested...
The precise role of CD4 T cell turnover in maintaining HIV persistence during antiretroviral therapy (ART) has not yet been well characterized. In resting subpopulations from 24 HIV-infected ART-suppressed and 6 HIV-uninfected individuals, we directly measured cellular by heavy water labeling, reservoir size integrated HIV-DNA (intDNA) cell-associated HIV-RNA (caRNA), clonality proviral integration site sequencing. Compared to HIV-negatives, individuals had similar fractional replacement...
Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction to medication that presents within 72 hours of exposure with erythematous papules and plaques overlying pustules. The immunopathogenesis predisposing factors AGEP are not well characterized. To better understand the genetic risk single-cell AGEP, we longitudinally characterized patient recurrent after an initial episode triggered by vancomycin. A clinical timeline over 8-year period was paired skin...
Developing an effective HIV-1 vaccine is a global health priority, but mutational escape from T cells poses challenge. While human leukocyte antigen class I (HLA-I)–restricted CD8 + well characterized, less known about HLA-II–restricted cell escape. We used computational methods to identify 149 sites across the clade B genome under HLA-II–associated selection. Functional assays, including activation-induced intracellular cytokine staining and enzyme-linked immunospot for interferon-γ,...
Persistent systemic inflammation is associated with an elevated risk of cardiometabolic diseases. However, the characteristics innate and adaptive immune systems in individuals who develop these conditions remain poorly defined. Doublets, or cell-cell complexes, are routinely eliminated from flow cytometric other phenotyping analyses, which limits our understanding their relationship to disease states. Using well-characterized clinical cohorts, including participants controlled human...
Submission Type: Total Ankle Arthroplasty Research Level 3 - Retrospective cohort study, Case-control Meta-analysis of studies Introduction/Purpose: Periprosthetic joint infections following total ankle arthroplasty occur at an estimated rate 2% to 8.6%, while surgical site in foot and surgery range from 4.5%. Despite these risks, there is limited evidence supporting the routine use antibiotic prophylaxis arthroplasty. This study aimed assess characteristics patients receiving perioperative...
The host's immune response to hepatitis C virus (HCV) can result in the selection of characteristic mutations (adaptations) that enable escape this response. ability mutate at these sites is dependent on incoming virus, fitness cost incurred by mutation, and benefit escaping Studies examining viral adaptation chronic HCV infection have shown be observed population level as human leukocyte antigen (HLA)–specific polymorphisms. We examined 63 individuals with who were infected from a single...
HIV-1 infection is characterized by the rapid generation of genetic diversity that facilitates viral escape from immune selection and antiretroviral therapy. Despite recombination's crucial role in evolution, little known about genomic factors influence recombination between highly similar genomes. In this study, we use a minimally modified full-length genome high-throughput sequence analysis to study gag pol T cells. We find favored at number hot spots, where occurs six times more...
Currently, 1.1 million individuals in the United States are living with HIV-1 infection. Although this is a relatively small proportion of global pandemic, remarkable mix ancestries States, drawn together over past two centuries continuous population migrations, provides an important and unique perspective on adaptive interactions between human genetic diversity. rapidly adaptable organism mutates within or near immune epitopes that determined by HLA class I genotype infected host. We...
ABSTRACT Hepatitis B virus (HBV)-specific T-cell responses are important in the natural history of HBV infection. The number known HBV-specific epitopes is limited, and it not clear whether viral evolution occurs chronic We aimed to identify novel by examining relationship between sequence variation human leukocyte antigen (HLA) type a large prospective clinic-based cohort Asian patients with infection recruited Australia China ( n = 119). High-resolution 4-digit HLA class I II typing...
To define the relative frequencies of different mechanisms viral escape.A population-based approach to examine distribution HIV polymorphism associated with diverse population human leucocyte antigens (HLAs) at sites within and flanking CD8 T-cell epitopes as a correlate likely escape.Sequence windows surrounding 874 HLA allele-specific polymorphisms across full HIV-1 proteomic consensus sequence were scanned by an epitope-prediction programme. Either already known or probable restriction...
ABSTRACT The interaction between hepatitis C virus (HCV) and cellular immune responses during very early infection is critical for disease outcome. To date, the impact of antigen-specific on evolution viral population establishing potential escape has not been studied. Understanding these host-virus dynamics important development a preventative vaccine. Three subjects who were followed longitudinally from detection viremia preseroconversion until outcome analyzed. transmitted/founder (T/F)...
Abstract Background Genetic variations across the SARS-CoV-2 genome may influence transmissibility of virus and host’s anti-viral immune response, in turn affecting frequency variants over-time. In this study, we examined adjacent amino acid polymorphisms nucleocapsid (R203K/G204R) that arose on background spike D614G change describe how strains harboring these changes became dominant circulating globally. Methods Deep sequencing data from public databases clinical samples were analyzed to...
Persons with HIV are at increased risk for diabetes mellitus compared individuals without HIV. Adipose tissue is an important regulator of glucose and lipid metabolism, adipose T cells modulate local inflammatory responses and, by extension, adipocyte function. have a high proportion CX3CR1+ GPR56+ CD57+ (C-G-C+) CD4+ in tissue, subset which cytomegalovirus specific, whereas but predominantly CD69+ cells. C-G-C+ cell subsets demonstrate higher receptor clonality the same blood, potentially...
Immune checkpoint therapy (ICT) causes durable tumour responses in a subgroup of patients, but it is not well known how T cell receptor beta (TCRβ) repertoire dynamics contribute to the therapeutic response. Using murine models that exclude variation host genetics, environmental factors and mutation burden, limiting between animals naturally diverse TCRβ repertoires, we applied TCRseq, single RNAseq flow cytometry study ICT responders non-responders. Increased oligoclonal expansion...