A5036830739- Immune Cell Function and Interaction
- HIV Research and Treatment
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Neonatal Respiratory Health Research
- Cytomegalovirus and herpesvirus research
- Tryptophan and brain disorders
- Tuberculosis Research and Epidemiology
- interferon and immune responses
- Preterm Birth and Chorioamnionitis
- Immunodeficiency and Autoimmune Disorders
- Infectious Diseases and Tuberculosis
- Electroconvulsive Therapy Studies
- Immune Response and Inflammation
- Gut microbiota and health
- NF-κB Signaling Pathways
- Immune responses and vaccinations
- Sperm and Testicular Function
- Pneumocystis jirovecii pneumonia detection and treatment
- Neonatal and Maternal Infections
- Immune cells in cancer
- Bacterial Infections and Vaccines
- Signaling Pathways in Disease
- Pharmacological Effects and Toxicity Studies
- IL-33, ST2, and ILC Pathways
Emory University
2021-2025
Case Western Reserve University
2018-2023
University of British Columbia
2011-2021
British Columbia Children's Hospital
2021
University Hospitals of Cleveland
2020
Cornell University
2020
Hennepin Healthcare Research Institute
2019
University of Nebraska Medical Center
2012-2019
Child and Family Research Institute
2010-2015
Loyola University Medical Center
2013-2014
STAT6 (signal transducer and activator of transcription 6) is a factor that plays central role in the pathophysiology allergic inflammation. We have identified 16 patients from 10 families spanning three continents with profound phenotype early-life onset immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, anaphylaxis. The cases were either sporadic (seven...
Newborn infants, including those born at term without congenital disorders, are high risk of severe disease from respiratory syncytial virus (RSV) infection. Indeed, our current local surveillance data demonstrate that approximately half children hospitalized with RSV were ≤3 mo old, and 74% term. Informed by this clinical epidemiology, we investigated antiviral innate immune responses in early life, the goal identifying immunological factors underlying susceptibility infants young to viral...
Abstract NK cell adoptive therapy is a promising cancer therapeutic approach, but there are significant challenges that limiting its feasibility and clinical efficacy. One difficulty the paucity of grade manufacturing platforms to support large scale expansion highly active cells. We created an feeder line termed ‘NKF’ through overexpressing membrane bound IL-21 capable inducing robust sustained proliferation (>10,000-fold at 5 weeks) cytotoxic The expanded cells exhibit increased...
Anti-CD19 chimeric antigen receptor T (CAR-T) cells have demonstrated activity against relapsed/refractory lymphomas. Cytokine release syndrome (CRS) and immune effector cell - associated neurotoxicity (ICANS) are well-known complications. Tocilizumab, a monoclonal antibody targeting the interleukin-6 (IL-6) was administered 1 hour prior to infusion of anti-CD19 CAR-T with CD3ζ/4-1BB costimulatory signaling used treat non-Hodgkin lymphoma patients. Relapsed/refractory patients treated were...
Chimeric antigen receptor T cells (CAR-T cell) targeting CD19 are effective against several subtypes of CD19-expressing hematologic malignancies. Centralized manufacturing has allowed rapid expansion this cellular therapy, but it may be associated with treatment delays due to the required logistics. We hypothesized that point care CAR-T on automated CliniMACS Prodigy® device allows reproducible and fast delivery for patients non-Hodgkin’s lymphoma. Here we describe cell results characterize...
HIV infection persists during antiretroviral therapy (ART) due to a reservoir of latently infected cells that harbor replication-competent virus and evade immunity. Previous ex vivo studies suggested CD8
Systemic lupus erythematosus (SLE) is characterized by dysregulated humoral immunity, leading to the generation of autoreactive B cells that can differentiate both within and outside lymph node (LN) follicles. Here, we employed spatial transcriptomics multiplex imaging investigate follicular immune landscaping in situ transcriptomic profile LNs from SLE individuals. Our analysis revealed robust type I IFN plasma cell signatures compared reactive, control Cell deconvolution T subsets are...
Chimeric antigen receptor (CAR) T cells targeting the CD19 are effective in treating adults and children with B-cell malignancies. Place-of-care manufacturing may improve performance accessibility by obviating need to cryopreserve transport centralized facilities. Here we develop an anti-CD19 CAR (CAR19) comprised of 4-1BB co-stimulatory TNFRSF19 transmembrane domains, showing anti-tumor efficacy vivo xenograft lymphoma model. CAR19 manufactured under current good practices (cGMP) at two...
Interleukin-1β (IL-1β) production is impaired in cord blood monocytes. However, the mechanism underlying this developmental attenuation remains unclear. Here, we analyzed extent of variability within Toll-like receptor (TLR)/NLRP3 inflammasome pathways human neonates. We show that immature low CD14 expressing/CD16(pos) monocytes predominate before 33 weeks gestation, and these cells lack pro-IL-1β precursor protein upon LPS stimulation. In contrast, high levels are produced expressing...
The metabolic signaling pathways that drive pathologic tissue inflammation and damage in humans with pulmonary tuberculosis (TB) are not well understood. Using combined methods plasma high-resolution metabolomics, lipidomics cytokine profiling from a multicohort study of TB disease, we discovered IL-1β-mediated inflammatory was closely associated TCA cycle remodeling, characterized by accumulation the proinflammatory metabolite succinate decreased concentrations anti-inflammatory itaconate....
Background Inflammation and infection are major determinants of disease severity consequently, the quality life outcome for patients with cystic fibrosis (CF). Interleukin-1 beta (IL-1β) is a key inflammatory mediator. Secretion biologically active IL-1β involves inflammasome-mediated processing. Little known about contribution inflammasomes in CF disease. This study examines production bronchial epithelial cell lines human CF. Results Bronchial were found to produce negligible amounts basal...
The persistence of virally infected cells as reservoirs despite effective antiretroviral therapy is a major barrier to an HIV/SIV cure. These are predominately contained within present in the B cell follicles (BCFs) secondary lymphoid tissues, site that characteristically difficult for most cytolytic antiviral effector penetrate. Here, we identified population NK macaque lymph nodes expressed BCF-homing receptor CXCR5 and accumulated BCFs during chronic SHIV infection. CXCR5+ follicular...
<b><i>Background:</i></b> Preterm neonates are highly vulnerable to infection. <b><i>Objectives:</i></b> To investigate the developmental contribution of prematurity, chorioamnionitis and antenatal corticosteroids (ANS) on maturation neonatal microbial pathogen recognition responses. <b><i>Methods:</i></b> Using standardized protocols, we assayed multiple inflammatory cytokine responses (IL-1β, IL-6, TNF-α IL-12/23p40)...
People living with HIV (PLWH) who are immune nonresponders (INRs) at greater risk of comorbidity and mortality than responders (IRs) restore their CD4+ T cell count after antiretroviral therapy (ART). INRs have low counts (<350 c/μL), heightened systemic inflammation, increased cycling (Ki67+). Here, we report the findings that memory cells plasma samples from several cohorts enriched in gut-derived bacterial solutes p-cresol sulfate (PCS) indoxyl (IS) both negatively correlated counts. In...
Introduction. Cervarix and Gardasil are two HPV vaccines with differing antigen adjuvant compositions. Gardasil-4 contains types 6, 11, 16 18 type-specific L1 viral like particles (VLPs) formulated amorphous AlHO9PS-3 adjuvant, while targets using AS04 (Al(OH)3 + TLR4 agonist MPL) to enhance immune response cross-protection against other high-risk types, not included in the vaccine. Methods. To investigate mechanisms of cross-neutralizing potential Cervarix, six monozygotic twins (12 females...
Point-of-care manufacture of chimeric antigen receptor (CAR)-T cells can significantly reduce the time from apheresis to infusion. We conducted a dual-institution phase I trial aimed evaluating safety and feasibility this manufacturing model. CASE 2417 was clinical trial. Adults with relapsed or refractory CD19 positive non-Hodgkin lymphoma (R/R NHL) treated ≥2 prior systemic therapies were eligible. MB-CART-19 is an anti-CD19 CAR T-cell product manufactured using CliniMACS Prodigy device...
Poor penetration of many anti-tuberculosis (TB) antibiotics into the central nervous system (CNS) is thought to be a major driver morbidity and mortality in TB meningitis (TBM). While amount particular drug that crosses cerebrospinal fluid (CSF) varies from person person, little known about host factors associated with interindividual differences CSF concentrations anti-TB drugs. In patients diagnosed TBM country Georgia (n = 17), we investigate association between multiple including serum...