A5103251975- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Drug-Induced Adverse Reactions
- Tuberculosis Research and Epidemiology
- Monoclonal and Polyclonal Antibodies Research
- Chemokine receptors and signaling
- Hepatitis C virus research
- Immunotherapy and Immune Responses
- HIV Research and Treatment
- IL-33, ST2, and ILC Pathways
- Cytomegalovirus and herpesvirus research
- Mycobacterium research and diagnosis
- Asthma and respiratory diseases
- Urticaria and Related Conditions
- vaccines and immunoinformatics approaches
- Atherosclerosis and Cardiovascular Diseases
- Diagnosis and treatment of tuberculosis
- Infectious Diseases and Tuberculosis
- Pluripotent Stem Cells Research
- Advanced Biosensing Techniques and Applications
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Hepatitis B Virus Studies
- Animal Virus Infections Studies
- SARS-CoV-2 and COVID-19 Research
UC San Diego Health System
2024
The University of Western Australia
2009-2023
Institute for Respiratory Health
2016-2022
Novem (Netherlands)
2022
Murdoch University
2007-2018
University of California, San Diego
2018
Harry Perkins Institute of Medical Research
2016
Queen Elizabeth II Medical Centre
2016
Princess Margaret Hospital for Children
2011
Royal Perth Hospital
2007-2011
Idiosyncratic adverse drug reactions are unpredictable, dose independent and potentially life threatening; this makes them a major factor contributing to the cost uncertainty of development. Clinical data suggest that many such involve immune mechanisms, genetic association studies have identified strong linkage between hypersensitivity several drugs specific HLA alleles. One strongest associations found has been for antiviral abacavir, which causes severe exclusively in patients expressing...
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with chronic inflammation and tissue remodelling leading to fibrosis, reduced function, respiratory failure death. Bleomycin (Blm)-induced in mice replicates several clinical features of human IPF, including prominent lymphoid aggregates predominantly B-cells that accumulate the adjacent areas active fibrosis. We have shown previously a requirement for development Blm-induced mice. To determine therapeutic...
Abstract —Chemokines are important mediators of macrophage and T-cell recruitment in a number inflammatory pathologies, chemokines expressed atherosclerotic lesions may play an role mononuclear cell differentiation. We have analyzed the expression linked chromosome 16q13 genes that encode macrophage-derived chemokine (MDC/CCL22), thymus- activation-regulated (TARC/CCL17), CX 3 C fractalkine (CX CL1) primary macrophages human by reverse transcription–polymerase chain reaction...
Chemokines are important mediators of inflammatory cell recruitment that play a significant role in atherosclerosis. Fractalkine (CX3CL1) is an unusual membrane-bound chemokine mediates chemotaxis through the CX3CR1 receptor. Recently, functional polymorphisms human gene have been described associated with coronary artery disease.We investigated expression CX3C fractalkine and its receptor plaques by immunocytometry. We show subset mononuclear cells expresses high levels atherosclerotic...
Abstract In vitro the mannose receptor (MR) mediates Ag internalization by dendritic cells (DC) and favors presentation of mannosylated ligands to T cells. However, in vivo MR seems play a role not but homeostatic clearance endogenous ligands, which could have secondary benefit reducing levels available for adaptive immune system. We now observed that while MR+ are consistently absent from cell areas spleen mesenteric lymph nodes (LN), peripheral LN untreated adult mice contain minor...
Background Fifty-five percent of individuals with HLA-B*57:01 exposed to the antiretroviral drug abacavir develop a hypersensitivity reaction (HSR) that has been attributed naïve T-cell responses neo-antigen generated by drug. Immunologically confirmed HSR can manifest clinically in less than 48 hours following first exposure suggesting that, at least some cases, is due re-stimulation pre-existing memory population rather priming high frequency population. Methods To determine whether...
<h3>Background</h3> Diagnosis of latent tuberculosis infection (LTBI) is a cornerstone the health assessment resettled high incidence populations, particularly in children. Two blood-based interferon γ release assays (IGRAs), T-SPOT.<i>TB</i> and QFT-Gold in-tube (QFT-GIT), have greater sensitivity specificity than tuberculin skin test (TST), but their performance as screening tools for LTBI children, especially refugee remains unclear. <h3>Methods</h3> 524 African ethnic Burmese including...
We reported previously that a proportion of natural CD25(+) cells isolated from the PBMC HCV patients can further upregulate CD25 expression in response to peptide stimulation vitro, and proposed virus-specific regulatory T (Treg) were primed expanded during disease. Here we describe epigenetic analysis FOXP3 locus HCV-responsive show these are not activated conventional expressing FOXP3, but hard-wired Treg with stable phenotype function. Of approximately 46,000 genes analyzed genome wide...
Objectives: This study sought to examine nevirapine hypersensitivity (NVP HSR) phenotypes and their relationship with differing major histocompatibility complex (MHC) Class I II alleles the associated CD4+ CD8+ T-cell NVP-specific responses durability over time. Methods: A retrospective cohort compared HIV-positive patients NVP HSR, defined by fever hepatitis and/or rash, those tolerant of for more than 3 months. Covariates included class (HLA-A, B, C) (HLA-DR) alleles. Cellular studies...
Atherosclerosis is a pathological process that takes place in the major arteries and underlying cause of heart attacks, stroke peripheral artery disease. The earliest detectable lesions, called fatty streaks, contain macrophage foam cells are derived from recruited monocytes. More-advanced atherosclerotic fibro-fatty plaques, result continued monocyte recruitment smooth muscle cell migration proliferation. Variable numbers CD4+ T found cytokines secreted by helper 1 (Th1)- or Th2-type can...
The introduction of highly active antiretroviral therapy (also known as combination therapy) has transformed the nature HIV infection from a severe and ultimately fatal disease to that manageable chronic condition. drugs are efficacious, but their use comes at cost range drug-related adverse events, including drug hypersensitivity reactions (HSRs) have been most notably associated with abacavir nevirapine therapy. This article discusses issues pharmacogenetic screening, in light strong...
HLA‐B57 and HLA‐B58 are major histocompatibility class (MHC)‐I allotypes that potentially predictive of important clinical immune phenotypes. HLA‐B*5701 is strongly associated with hypersensitivity to the HIV drug abacavir, liver toxicity from antibiotic flucloxacillin a marker for slow progression AIDS. HLA‐B*5801 allopurinol used treat hyperuricaemia recurrent gout. Here we describe monoclonal antibody (mAb) specific provides an inexpensive sensitive screen these MHC‐I allotypes. The...
Abstract Background Infection prevention (IP) measures are designed to mitigate the transmission of pathogens in healthcare. Using large-scale viral genomic and social network analyses, we determined if IP used during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were adequate protecting healthcare workers (HCWs) patients from acquiring SARS-CoV-2. Methods We performed retrospective cross-sectional analyses genomics all available SARS-CoV-2 samples collected at UC San...
Cellular immune responses during acute Hepatitis C virus (HCV) and HIV infection are a known correlate of outcome. Viral adaptation to these via mutation(s) within CD8+ T-cell epitopes allows viruses subvert host control. This study examined HCV evolution in 21 genotype 1-infected subjects characterise the level viral early infection. Of total mutations observed 25% were described or at sites. Most maintained into chronic phase (75%). The lack reversion adaptations high proportion silent...
The lung achieves an efficient gas exchange between a complex non-sterile atmosphere and the body via delicate extensive epithelial surface, with high efficiency because of elastic deformation allowing for increase decrease in volume during process breathing vasculature which aids rapid diffusion. lungs' large surface area exposes organ to continual risk damage from pathogens, toxins or irritants; however, can be rapidly healed regenerative processes that restore its structure function. In...
Environmental changes affecting the relationship between developing immune system and microbial exposure have been implicated in epidemic rise of allergic disease developed countries. While early developmental differences T cell function are well-recognised, there is now emerging evidence that this related to innate function. In study we sought examine if associated with immunity contribute altered programming recognised children. Here, describe for first time, association carriage allele...
Since the discovery of induced pluripotent stem cells (iPSC) in 2006, symptoms many human diseases have been reversed animal models with iPSC therapy, setting stage for future clinical development. From data it is clear that are rapidly becoming lead cell type replacement therapy and newly developing field iPSC-derived body organ transplantation. The first pathology might be treated near age-related macular degeneration (AMD), which has recently passed criteria set down by regulators phase I...
Summary. Classic studies of tuberculosis (TB) revealed morphologic evidence considerable heterogeneity macrophages (MØs), but the functional significance this remains unknown. We have used newly available specific antibodies for selected membrane and secretory molecules to examine phenotype MØs in situ a range South African patients with TB, compared sarcoidosis. Patients were human immunodeficiency virus‐negative adults children, examined biopsy specimens included lung lymph nodes. Mature...
Hepatitis C virus (HCV)-specific T cell responses are critical for immune control of infection. Viral adaptation to these responses, via mutations within regions the targeted by CD8+ cells, is associated with viral persistence. However, identifying HCV-specific CD4+ has been difficult although key understanding anti-HCV immunity. In this context, HCV sequence and host genotype from a single source 1B cohort (n = 63) were analyzed identify changes specific human leucocyte antigen (HLA) class...