A5002329912- Reproductive tract infections research
- Syphilis Diagnosis and Treatment
- Gut microbiota and health
- Cytomegalovirus and herpesvirus research
- Cervical Cancer and HPV Research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- COVID-19 Clinical Research Studies
- Urinary Tract Infections Management
- SARS-CoV-2 and COVID-19 Research
- Immune Response and Inflammation
- Transplantation: Methods and Outcomes
- Clostridium difficile and Clostridium perfringens research
- Long-Term Effects of COVID-19
- Renal Transplantation Outcomes and Treatments
- Child Nutrition and Water Access
- Herpesvirus Infections and Treatments
- Extracellular vesicles in disease
- Bacterial Identification and Susceptibility Testing
- Influenza Virus Research Studies
- Dermatology and Skin Diseases
- Monoclonal and Polyclonal Antibodies Research
- Antimicrobial Resistance in Staphylococcus
- interferon and immune responses
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
University of California, Los Angeles
2021-2025
London School of Hygiene & Tropical Medicine
2016-2024
UCLA Health
2022-2024
University of London
2017-2022
University of Edinburgh
2012
Abstract Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim understand the host immunologic and microbial features of COVID-19 in recipients by leveraging a prospective multicenter cohort 86 age- sex-matched with 172 non-transplant controls. find that higher nasal SARS-CoV-2 viral abundance impaired clearance, lower anti-spike IgG levels. In addition, exhibit...
IL-12 is an essential cytokine involved in the generation of memory or memory-like NK cells. Mouse cytomegalovirus infection triggers receptor-induced, ligand-specific IL-12-dependent cell expansion, yet specific stimulation ex vivo leading to proliferation and expansion not established. Here, we show that alone can sustain human primary survival without providing IL-2 IL-15 but was insufficient promote proliferation. signaling analysis revealed STAT5 phosphorylation weak mTOR activation,...
Cytomegalovirus (CMV) infection is associated with graft rejection in renal transplantation. Memory-like natural killer (NK) cells expressing NKG2C and lacking FcεRIγ are established during CMV infection. Additionally, CD8
Age is a major risk factor for severe coronavirus disease 2019 (COVID-19), yet the mechanisms behind this relationship have remained incompletely understood. To address this, we evaluated impact of aging on host immune response in blood and upper airway, as well nasal microbiome prospective, multicenter cohort 1031 vaccine-naïve patients hospitalized COVID-19 between 18 96 years old. We performed mass cytometry, serum protein profiling, anti–severe acute respiratory syndrome 2 (SARS-CoV-2)...
Mass drug administration (MDA) with azithromycin is the primary strategy for global trachoma control efforts. Numerous studies have reported secondary effects of MDA azithromycin, including reductions in childhood mortality, diarrhoeal disease and malaria. Most recently, MORDOR clinical trial demonstrated that led to an overall reduction all-cause mortality targeted communities. There however concern about potential increased antimicrobial resistance treated This study evaluated impact on...
Abstract Influenza virus infection alters the promoter DNA methylation of key immune response-related genes, including type-1 interferons and proinflammatory cytokines. However, less is known about effect influenza vaccine on epigenome. We utilized a targeted approach to study longitudinal effects (day 0 pre-vaccination day 28 post-vaccination) vaccination responses in peripheral blood mononuclear cells. found that baseline, profiles are associated with pre-existing, protective serological...
Abstract Background Infectious complications continue to cause significant morbidity and mortality after kidney transplantation (KTx), especially in older patients where immune senescence increases impact of immunosuppression. Given the importance T cell function epigenetic regulation infection vulnerability, we sought evaluate whether DNA methylome phenotypes could predict development KTx. Principal component analysis (PCA) CD4 CD8 subsets associated with PBMC collected pre (green) compared...
Introduction Cytomegalovirus (CMV) viremia remains a major contributor to clinical complications in solid organ transplant (SOT) patients, including injury, morbidity and mortality. Given their critical role antiviral defense, CD8+ T cells are essential for protective immunity against CMV. Methods Using single-cell RNA sequencing, we investigated the transcriptional signatures developmental lineages of eight immunosuppressed kidney recipients (KTRs) who received organs from CMV-seropositive...
Abstract Background Staphylococcus aureus bacteremia (SAB) is a prevalent life-threatening infection often caused by methicillin-resistant S. (MRSA). Up to 30% of SAB patients fail clear even with gold-standard anti-MRSA antibiotics. This phenomenon termed antibiotic-persistent MRSA (APMB). The mechanisms driving APMB are complex and involve host phenotypes significantly impacting the immune response. Thus, defining early signatures clinical that differentiate from antibiotic resolving...
Cytomegalovirus (CMV) infection threatens outcomes across solid organ transplantation, but organ-specific differences in CMV immunity are incompletely understood. We investigated whether lung and kidney drove similar immune profiles, hypothesizing that CMV-associated T cells would be associated with graft function. longitudinally examined 41 transplant (LTx) recipients 31 (KTx) viremia, alongside non-viremic controls. performed flow cytometry single-cell protein transcriptomic profiling...
Trachoma, a neglected tropical disease caused by Chlamydia trachomatis (Ct) serovars A–C, is the leading infectious cause of blindness worldwide. Africa bears highest burden, accounting for over 86 % global trachoma cases. We investigated Ct serovar A (SvA) and B (SvB) whole genome sequences prior to induction mass antibiotic drug administration in The Gambia. Here, we explore factors contributing strain diversification implications evolution within context ocular infection. cohort study...
Chronic viral infections are ubiquitous in humans, with individuals harboring multiple latent viruses that can reactivate during acute illnesses. Recent studies have suggested SARS-CoV-2 infection lead to reactivation of such as Epstein-Barr Virus (EBV) and cytomegalovirus (CMV), yet, the extent impact COVID-19 its effect on host immune system remain incompletely understood. Here we present a comprehensive multi-omic analysis all known chronically infecting 1,154 hospitalized patients, from...
Kidney transplantation (KTx) is the method of choice for treating kidney failure. Identifying biomarkers predictive transplant (Tx) outcomes critical to optimize KTx; however, immunosuppressive therapies required after KTx must also be considered. We applied targeted bisulfite sequencing (TBS-seq) PBMCs isolated from 90 patients, with samples collected pre- and post-Tx (day 90), measure DNA methylation changes. Our findings indicate that PBMC methylome significantly affected by induction...
In some Pacific Island countries, such as Solomon Islands and Fiji, active trachoma is common, but ocular Chlamydia trachomatis (Ct) infection trachomatous trichiasis (TT) are rare. On Tarawa, the most populous Kiribati island, both sign "trachomatous inflammation-follicular" (TF) TT present at prevalences warranting intervention. We sought to estimate of TF, TT, Ct infection, anti-Ct antibodies on Kiritimati Island, Kiribati, assess local relationships between these parameters, help...
Abstract Trachoma is caused by Chlamydia trachomatis (Ct). It targeted for global elimination as a public health problem. In 2014, population-based cross-sectional study was performed in two previously trachoma-endemic areas of The Gambia. Participants all ages from Lower River Region (LRR) (N = 1028) and Upper (URR) 840) underwent examination trachoma had blood collected detection antibodies against the Ct antigen Pgp3, ELISA. Overall, 30 (1.6%) individuals active trachoma; prevalence...
CMV causes mostly asymptomatic but lifelong infection. Primary infection or reactivation in immunocompromised individuals can be life-threatening. viremia often occurs solid organ transplant recipients and associates with decreased graft survival higher mortality. Furthering understanding of impaired immunity that allows is critical to guiding antiviral therapy examining the effect on outcomes. This study characterized longitudinal immune responses 31 kidney matched, nonviremic recipients....
NKG2C is an activating receptor that preferentially expressed on natural killer (NK) cells. The gene encoding (killer cell lectin-like C2, KLRC2) present at different copy numbers in the genomes of individuals. Deletion locus was investigated a case–control study 1522 individuals indigenous to East- and West-Africa association with ocular Chlamydia trachomatis infection its sequelae explored. frequency homozygous KLRC2 deletion 13.7 % Gambians 4.7 Tanzanians. A significantly higher allele...
Abstract Cytokine-induced memory-like (CIML) NK cells generated in response to proinflammatory cytokines vitro and vivo can also be by vaccination, exhibiting heightened responses cytokine stimulation months after their initial induction. Our previous study demonstrated that human cell inactivated influenza virus were indirectly augmented very low doses of IL-15, which increased induction myeloid cell–derived secretion. These findings led us hypothesize IL-15 could reveal a similar effect...
In the peri-elimination setting, positive predictive value of trachomatous inflammation-follicular (TF), primary marker used to determine need for antibiotics trachoma, is suboptimal. Here, three non-TF measures are compare two regions where TF prevalence exceeds threshold intervention, but Chlamydia trachomatis (Ct) different.Population trachoma was measured in Vanuatu (n = 3470) and Kiribati 2922). Dried blood spots (DBS) conjunctival photographs were collected from every survey...
To eliminate trachoma as a public health problem, the World Health Organization recommends SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) strategy. As part of strategy in Amhara Region, Ethiopia, Trachoma Control Program distributed >124 million doses antibiotics between 2007 2015. Despite this, remained hyperendemic many districts considerable level Chlamydia trachomatis (Ct) infection was evident.We utilized residual material from Abbott m2000 Ct diagnostic...
Abstract Age is a major risk factor for severe coronavirus disease-2019 (COVID-19), yet the mechanisms responsible this relationship have remained incompletely understood. To address this, we evaluated impact of aging on host and viral dynamics in prospective, multicenter cohort 1,031 patients hospitalized COVID-19, ranging from 18 to 96 years age. We performed blood transcriptomics nasal metatranscriptomics, measured peripheral immune cell populations, inflammatory protein expression,...
Introduction Staphylococcus aureus bacteremia (SAB) is a life-threatening infection particularly involving methicillin-resistant S. (MRSA). In contrast to resolving MRSA (RB), persistent (PB) blood cultures remain positive despite appropriate antibiotic treatment. Host immune responses distinguishing PB vs. RB outcomes are poorly understood. Here, integrated transcriptomic, IL-10 cytokine levels, and genomic analyses sought identify signatures differentiating outcomes. Methods Whole-blood...
Abstract Background The effect of vaccination on the epigenome remains poorly characterized. In previous research, we identified an association between seroprotection against influenza and DNA methylation at sites associated with RIG-1 signaling pathway, which recognizes viral double-stranded RNA leads to a type I interferon response. However, these studies did not fully account for confounding factors including age, gender, BMI, along changes in cell-type composition. Results Here, studied...
Chlamydia trachomatis (Ct) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide. Ct strain-specific differences in clinical trachoma suggest that genetic polymorphisms may contribute to observed variability severity disease. Using whole genome sequences obtained directly from conjunctival swabs, we studied genomic diversity associations between with ocular localization disease a treatment-naïve trachoma-endemic population Guinea-Bissau, West...