- Immunotherapy and Immune Responses
- Salmonella and Campylobacter epidemiology
- Cancer Research and Treatments
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- RNA Interference and Gene Delivery
- T-cell and B-cell Immunology
- Aquaculture disease management and microbiota
- Mycobacterium research and diagnosis
- Bacteriophages and microbial interactions
- Respiratory viral infections research
- Nanoparticle-Based Drug Delivery
- Tuberculosis Research and Epidemiology
- Allergic Rhinitis and Sensitization
- Food Allergy and Anaphylaxis Research
- Graphene and Nanomaterials Applications
- Immune Response and Inflammation
- Wound Healing and Treatments
- Viral gastroenteritis research and epidemiology
- Escherichia coli research studies
- Pressure Ulcer Prevention and Management
- Advanced Biosensing Techniques and Applications
- Economic, financial, and policy analysis
- Healthcare Operations and Scheduling Optimization
University of Chicago
2021-2024
Worcester Polytechnic Institute
2017
Veterans Health Administration
2017
University of California, Davis
2015
University of Aberdeen
2011
University of Saskatchewan
2009-2010
University of Southampton
2009-2010
Newcastle University
2009-2010
University of Reading
2009-2010
Université Sorbonne Paris Nord
2009-2010
Butyrate-a metabolite produced by commensal bacteria-has been extensively studied for its immunomodulatory effects on immune cells, including regulatory T macrophages and dendritic cells. However, the development of butyrate as a drug has hindered butyrate's poor oral bioavailability, owing to rapid metabolism in gut, low potency (hence, necessitating high dosing), foul smell taste. Here we report that bioavailability can be increased esterifying it serine, an amino acid transporter aids...
The COVID-19 pandemic underscores the need for rapid, safe, and effective vaccines. In contrast to some traditional vaccines, nanoparticle-based subunit vaccines are particularly efficient in trafficking antigens lymph nodes, where they induce potent immune cell activation. Here, we developed a strategy decorate surface of oxidation-sensitive polymersomes with multiple copies SARS-CoV-2 spike protein receptor-binding domain (RBD) mimic physical form virus particle. We evaluated vaccination...
The SARS-CoV-2 virus has caused an unprecedented global crisis, and curtailing its spread requires effective vaccine which elicits a diverse robust immune response. We have previously shown that vaccines made of polymeric glyco-adjuvant conjugated to antigen were in triggering such response other disease models hypothesized the technology could be adapted create against SARS-CoV-2. core platform is copolymer p(Man-TLR7), composed monomers with pendant mannose or toll-like receptor 7 (TLR7)...
Immune stimulating agents like Toll-like receptor 7 (TLR7) agonists induce potent antitumor immunity but are limited in their therapeutic window due to off-target immune activation. Here, we developed a polymeric delivery platform that binds excess unpaired cysteines on tumor cell surfaces and debris adjuvant neoantigens as an situ vaccine. The metabolic enzymatic dysregulation the microenvironment produces these exofacial free thiols, which can undergo efficient disulfide exchange with...
Although most current treatments for autoimmunity involve broad immunosuppression, recent efforts have aimed to suppress T cells in an antigen-specific manner minimize risk of infection. One such effort is through targeting antigen the apoptotic pathway increase presentation interest a tolerogenic context. Erythrocytes present rational candidate target because their high rate eryptosis, which facilitates continual uptake by antigen-presenting spleen. Here, we develop approach that binds...
The only FDA-approved oral immunotherapy for a food allergy provides protection against accidental exposure to peanuts. However, this therapy often causes discomfort or side effects and requires long-term commitment. Better preventive therapeutic solutions are urgently needed. We develop tolerance-inducing vaccine technology that utilizes glycosylation-modified antigens induce antigen-specific non-responsiveness. administered intravenously (i.v.) subcutaneously (s.c.) traffic the liver lymph...
Immunogenic biologics trigger an anti-drug antibody (ADA) response in patients that reduces efficacy and increases adverse reactions. Our laboratory has shown targeting protein antigen to the liver microenvironment can reduce antigen-specific T cell responses; herein, we present a strategy increase delivery of otherwise immunogenic via conjugation synthetic mannose polymer, p(Man). This leads reduced follicular helper B responses resulting diminished ADA production, which is maintained...
Salmonella typhimurium hybrids expressing the S. typhosa antigens 9, d, and Vi were constructed by genetic crosses with an Hfr donor. The retained same degree of mouse virulence as their parent strain, minimum lethal dose being less than 50 organisms when tested either in C 57 black mice or Swiss white mice. Vaccination Ty2 vaccines prepared acetone treatment, alcohol heat-killing conferred significant protection against challenge hybrid strains but not parent. Both acetone-treated...
S. typhi spheroplasts were produced by growing typhoid organisms in a liquid semisynthetic medium containing 1.5 to 2.0% glycine. The addition of traces magnesium and glucose concentrations 0.5 was required for optimal growth conditions. These cells considered be the transition L form since they reproduced as long grown glycine medium, but unlike true organism reverted normal bacillary when subcultured glycine-free medium.The lytic susceptibility studied. They found resistant number...
Non-healing wounds have a negative impact on quality of life and account for many cases amputation even early death among patients. Diabetic patients are the predominate population affected by these non-healing wounds. Despite significant clinical demand, treatment with biologics has not broadly impacted care. Interleukin-4 (IL-4) is potent modulator immune system, capable skewing macrophages towards pro-regeneration phenotype (M2) promoting angiogenesis, but can be toxic after frequent...
Swiss white mice immunized with acetone-killed vaccines prepared from strains of Salmonella typhosa, S. typhimurium , and mouse-virulent hybrids which had acquired, by conjugal genetic transfer, the typhosa antigens 9, Vi, d were challenged parent strain. The results these experiments suggested that somatic important in conferring protection against death this system. Vi antigen did not appear to play any significant role protection. employed studies show loss mouse virulence as consequence...
ABSTRACT A diverse portfolio of SARS-CoV-2 vaccine candidates is needed to combat the evolving COVID-19 pandemic. Here, we developed a subunit nanovaccine by conjugating Spike protein receptor binding domain (RBD) surface oxidation-sensitive polymersomes. We evaluated humoral and cellular responses mice immunized with these surface-decorated polymersomes (RBD surf ) compared RBD-encapsulated encap unformulated RBD free ), using monophosphoryl lipid A-encapsulated (MPLA PS) as an adjuvant....
Summary The only FDA-approved oral immunotherapy for a food allergy provides protection against accidental exposure to peanuts. However, this therapy often causes discomfort or side effects and requires long-term commitment. Better preventive therapeutic solutions are urgently needed. We have developed tolerance-inducing vaccine technology that utilizes glycosylation-modified antigens induce antigen-specific non-responsiveness. were administered intravenously (i.v.) subcutaneously (s.c.)...
Immunogenic biologics trigger an anti-drug antibody (ADA) response in patients, which reduces efficacy and increases adverse reactions. Our laboratory has previously shown that targeting protein antigen to the liver microenvironment can reduce antigen-specific T cell responses; herein, we present a strategy increase delivery of otherwise immunogenic via conjugation synthetic mannose polymer (p(Man)). This leads reduced follicular helper B responses resulting diminished ADA production, is...
EXECUTIVE SUMMARY The patient-centered medical home (PCMH) has been proposed as a viable and medically effective model of primary care delivery. fundamental principles PCMH address increased access offer new ways to organize practice. Creating provider schedules able satisfy the operational organizational constraints imposed by this type delivery is challenging, complex, time-consuming task. This article presents two-step approach for scheduling providers prospectively assessing consequences...
Purified Vi antigen, acetic anthydride-treated Salmonella typhosa endotoxin, and potassium methylate-treated S. endotoxin employed as vaccines in Swiss white mice failed to protect these animals against challenge with a virulent typhimurium hybrid expressing antigens.
The serological activity of glycine-induced spheroplasts and normal intact cells Salmonella typhi was assessed. No major differences could be detected in the somatic O Vi antigens cells. only change associated with transformation typhoid organisms into seems to flagellar antigen. Spheroplasts evoked a high H agglutinin response immunized rabbits but were poorly agglutinated by standard antiserum.The immunogenic ability protect mice from challenge about five times higher than that toxicity...
Abstract Immune reactions to protein drugs present substantial challenges replacement for treating congenital diseases and metabolic deficiencies, due the lack of endogenous tolerance or drug’s partial total non-human origin. We sought transiently modify immune environment when adaptive response drug antigen is mounted lessen future upon continued therapeutic treatment, without modifying itself. Herein, we characterize a recombinant fusion cytokine Flt3L serum albumin describe novel pathway...
The properties of glycine-induced spheroplasts six pathogenic serotypes E. coli were investigated. Fimbriae and flagella appeared to be only partially synthesized as was the somatic O antigen. Cytopathogenicity these for tissue culture reduced infection monolayers retarded compared with normal bacillary forms. Sensitivity phage almost completely lost, suggesting that glycine had either interfered synthesis receptors or altered mucopeptide layerwhich is substrate enzymes. Alternatively, may...
Biological studies of suspensions S. typhi, lysed with the enzyme dornase, have shown that dornase alters their immunogenic capacity to some extent. However, when prior treatment bacterial suspension by sonic oscillation hastened breakdown process, did not impair protective ability typhoid vaccine, although it eliminated most its toxicity. In spite differences found in and toxicity, all fractions were active eliciting pyrogen effect Shwartzman phenomenon.
Live Salmonella typhi administered intraperitoneally, acetone-killed S. and live given orally, with their effectiveness decreasing in that order, protected Swiss white mice against death from challenge a virulent typhimurium hybrid expressing antigens.