Sean Bickerton
A5029191536- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Nanoparticle-Based Drug Delivery
- COVID-19 Clinical Research Studies
- RNA Interference and Gene Delivery
- SARS-CoV-2 and COVID-19 Research
- Immunotherapy and Immune Responses
- Long-Term Effects of COVID-19
- Systemic Lupus Erythematosus Research
- COVID-19 diagnosis using AI
- Advanced Polymer Synthesis and Characterization
- Pancreatic function and diabetes
- Reproductive System and Pregnancy
- Advanced Drug Delivery Systems
- CAR-T cell therapy research
- Anesthesia and Neurotoxicity Research
- Hydrogels: synthesis, properties, applications
- COVID-19 and Mental Health
- Surfactants and Colloidal Systems
- Dendrimers and Hyperbranched Polymers
- Supramolecular Chemistry and Complexes
- Cell Image Analysis Techniques
- Psoriasis: Treatment and Pathogenesis
- Biosensors and Analytical Detection
- COVID-19 Impact on Reproduction
Yale University
2015-2024
University of Massachusetts Amherst
2010-2012
There is increasing evidence that coronavirus disease 2019 (COVID-19) produces more severe symptoms and higher mortality among men than women1–5. However, whether immune responses against acute respiratory syndrome (SARS-CoV-2) differ between sexes, such differences correlate with the sex difference in course of COVID-19, currently unknown. Here we examined viral loads, SARS-CoV-2-specific antibody titres, plasma cytokines blood-cell phenotyping patients moderate COVID-19 who had not...
Nanoscopic vehicles that stably encapsulate drug molecules and release them in response to a specific trigger are of great interest due implications therapeutic applications, especially for cancer therapy. For this purpose, we have synthesized highly stable polymeric nanogels, which the kinetics guest molecule can be fine-tuned by control over cross-linking density. The polymer nanogel precursor is based on random copolymer contains oligoethyleneglycol (OEG) pyridyldisulfide (PDS) units as...
Abstract Although microbial populations in the gut microbiome are associated with COVID-19 severity, a causal impact on patient health has not been established. Here we provide evidence that dysbiosis is translocation of bacteria into blood during COVID-19, causing life-threatening secondary infections. We first demonstrate SARS-CoV-2 infection induces mice, which correlated alterations to Paneth cells and goblet cells, markers barrier permeability. Samples collected from 96 patients at two...
The stability of encapsulation in self-assembly systems is limited during blood circulation because a requisite concentration for assembly formation. For deliberate molecular design stable encapsulation, targeting, and triggered release, we have developed facile synthetic method highly stable, polymeric nanogels using simple intra/interchain cross-linking reaction. We show simple, emulsion-free the preparation biocompatible that provides ability to encapsulate hydrophobic guest molecules...
Exchange dynamics of lipophilic guest molecules, encapsulated in supramolecular nanoassemblies aqueous solutions, have implications evaluating the stability drug delivery vehicles. This is because exchange related to propensity a nanocarrier be leaky. We describe fluorescence resonance energy transfer (FRET) based method evaluate phase. utilized this analyze encapsulation polymeric nanogels and other amphiphilic nanoassemblies.
Podocyte malfunction occurs in autoimmune and nonautoimmune kidney disease. Calcium signaling is essential for podocyte injury, but the role of Ca2+/calmodulin-dependent kinase (CaMK) podocytes has not been fully explored. We report that from patients with lupus nephritis focal segmental glomerulosclerosis lupus-prone lipopolysaccharide- or adriamycin-treated mice display increased expression CaMK IV (CaMK4), CaMK2. Mechanistically, CaMK4 modulated motility by altering GTPases Rac1 RhoA...
Nanoscale vehicles for delivery have been of interest and extensively studied two decades. However, the encapsulation stability hydrophobic drug molecules in selective targeting these into disease cells are potential hurdles efficient systems. Here we demonstrate a simple fast synthetic protocol nanogels that shows high stabilities. These can also be modified with various ligands active targeting. We show (T-NGs), which prepared within 2 h by one-pot synthesis, exhibit very narrow size...
Abstract Treatment of autoimmune diseases is still largely based on the use systemically acting immunosuppressive drugs, which invariably cause severe side effects. Calcium/calmodulin-dependent protein kinase IV involved in suppression IL-2 and production IL-17. Its pharmacologic or genetic inhibition limits disease mice. In this study, we demonstrate that KN93, a small-molecule inhibitor calcium/calmodulin-dependent IV, targeted to CD4+ T cells via nanolipogel delivery system, markedly...
Objective To develop a nanoparticle ( NP ) platform that can expand both CD 4+ and 8+ Treg cells in vivo for the suppression of autoimmune responses systemic lupus erythematosus SLE ). Methods Poly(lactic‐co‐glycolic acid) PLGA s encapsulating interleukin‐2 IL ‐2) transforming growth factor β TGF β) were coated with anti‐ 2/ 4 antibodies administered to mice lupus‐like disease induced by transfer DBA /2 T into (C57 BL /6 × /2)F 1 BDF 1) mice. The peripheral frequency was monitored ex flow...
Defective DNA methylation in T cells leads to a series of cell abnormalities lupus; however, the full effect lineage–specific on disease expression has not been explored. Here, we show that 5-azacytidine, methyltransferase inhibitor, targeted either CD4 or CD8 mice with established using nanolipogel delivery system dramatically ameliorates lupus-related pathology through distinct mechanisms. In vivo 5-azacytidine into favors expansion and function Foxp3+ Tregs, whereas enhances cytotoxicity...
A 22-month-old male infant presented with cyanosis and stridor after a trivial fall then developed acute respiratory distress. The status of the patient progressed rapidly to severe distress syndrome. Additional findings hypersplenism prompted comprehensive multidisciplinary approach consideration an inborn error metabolism. Rapid whole-genome sequence showed compound heterozygote mutation in GBA1 gene involving maternally inherited known pathogenic variant, p.L484P, paternally novel likely...
Significance Chilblain diagnoses have increased during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and been attributed to viral infection a subsequent robust antiviral immune response. As result, providers managed these cases differently than idiopathic chilblains, which are associated with cold exposure. The relationship between chilblains SARS-CoV-2 infection, however, remains unclear as most patients do not test positive for SARS-CoV-2–specific PCR or...
Polymer-based nanoassemblies have emerged as viable platforms for the encapsulation and delivery of lipophilic molecules. Among criteria that such carriers must meet, if they are to be effective, abilities efficiently solubilize guests within an assembled scaffold stably encapsulate molecular cargo until desired release is achieved through actions appropriately chosen stimuli. The former feature, dictated by inherent loading capacity a nanocarrier, well studied, it has been established...
Artificial antigen-presenting cells (aAPCs) are synthetic versions of naturally occurring (APCs) that, similar to natural APCs, promote efficient T effector cell responses in vitro . This report describes a method produce acellular tolerogenic aAPCs made biodegradable poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and encapsulating IL-2 TGF-β for paracrine release cells. We document that these can induce both human CD4 + CD8 become FoxP3 regulatory (Tregs). The aAPC NP-expanded...
We have previously reported that nanoparticles (NPs) loaded with IL-2 and TGF-β targeted to T cells induced polyclonal regulatory (Tregs) protected mice from graft-versus-host disease (GvHD). Here, we evaluated whether administration of these NPs during alloantigen immunization could prevent allograft rejection by converting immunogenic responses tolerogenic ones. Using C57BL/6 BALB/c as either donors or recipients allogeneic splenocytes, found treatment the in both strains resulted a marked...
Abstract Over the last century, outbreaks and pandemics have occurred with disturbing regularity, necessitating advance preparation large-scale, coordinated response. Here, we developed a machine learning predictive model of disease severity length hospitalization for COVID-19, which can be utilized as platform future unknown viral outbreaks. We combined untargeted metabolomics on plasma data obtained from COVID-19 patients (n = 111) during healthy controls 342), clinical comorbidity 508) to...
Multiple sclerosis (MS) is a demyelinating autoimmune disease that attacks the brain, with year-on-year loss of brain volume, starting late teens and becoming manifest twenties. There no cure, current therapies are immunosuppressive only. LIF vital stem cell growth factor active throughout life-and essential for health central nervous system (CNS), being tolerogenic, myelinogenic, neuroprotective. Nano-formulation (LIFNano) using FDA-approved PLGA captures LIF's compound therapeutic...