A5056109558- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Research and Treatments
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Reproductive System and Pregnancy
- Peptidase Inhibition and Analysis
- Antifungal resistance and susceptibility
- Immune Response and Inflammation
- Dietetics, Nutrition, and Education
- Cytomegalovirus and herpesvirus research
- Tissue Engineering and Regenerative Medicine
- Monoclonal and Polyclonal Antibodies Research
- Viral Infectious Diseases and Gene Expression in Insects
- Single-cell and spatial transcriptomics
- Biosimilars and Bioanalytical Methods
- Herpesvirus Infections and Treatments
- Advanced Drug Delivery Systems
- Influenza Virus Research Studies
- Musculoskeletal pain and rehabilitation
- IL-33, ST2, and ILC Pathways
- Ferroptosis and cancer prognosis
- Cultural Competency in Health Care
Takeda (United States)
2019-2025
Mount Saint Vincent University
2018-2021
University of Minnesota Medical Center
2005-2019
Biota Pharmaceuticals (United States)
2016-2019
Biothera (United States)
2015-2019
University of Minnesota
2009-2019
ProThera Biologics (United States)
2015-2018
Institute of Immunology
2015
Society for Ambulatory Anesthesia
2012
Community Connections
2012
Memory CD8 T cells protect against intracellular pathogens by scanning host cell surfaces; thus, infection detection rates depend on memory number and distribution. Population analyses rely isolation from whole organs, interpretation is predicated presumptions of near complete recovery. Paradigmatically, parsed into central, effector, resident subsets, ostensibly defined immunosurveillance patterns but in practice identified phenotypic markers. Because methods ultimately inform models...
The pathogen recognition theory dictates that, upon viral infection, the innate immune system first detects microbial products and then responds by providing instructions to adaptive CD8 T cells. Here, we show in mice that tissue resident memory cells (T(RM) cells), non-recirculating located at common sites of can achieve near-sterilizing immunity against infections reversing this flow information. Upon antigen resensitization within mouse female reproductive mucosae, CD8(+) T(RM) secrete...
Abstract Differentiation and maintenance of recirculating effector memory CD8 T cells (TEM) depends on prolonged cognate Ag stimulation. Whether similar pathways differentiation exist for recently identified tissue-resident (TRM), which contribute to rapid local protection upon pathogen re-exposure, is unknown. Memory CD8αβ+ within small intestine epithelium are well-characterized examples TRM, they maintain a long-lived effector-like phenotype that highly suggestive persistent This study...
Migration to intestinal mucosa putatively depends on local activation because gastrointestinal lymphoid tissue induces expression of homing molecules, whereas skin-draining lymph nodes do not. This paradigm is difficult reconcile with reports T cell responses after alternative routes immunization. We this discrepancy by demonstrating that within spleen results in intermediate induction potential the mucosa. further demonstrate memory cells small intestine epithelium not routinely recirculate...
Resident memory CD8 T cells (TRM) are a nonrecirculating subset positioned in nonlymphoid tissues to provide early responses reinfection. Although TRM associated with tissues, we asked whether they populated secondary lymphoid organs (SLO). We show that of virus-specific SLO exhibit phenotypic signatures TRM, including CD69 expression. Parabiosis revealed CD69(+) do not circulate, defining them as TRM. were overrepresented IL-15-deficient mice, suggesting independent regulation compared...
This study examines the extent to which memory CD4+ T cells share immunosurveillance strategies with CD8+ resident (TRM). After acute viral infection, predominantly used residence survey nonlymphoid tissues, albeit not as stringently observed for cells. In contrast, were more likely be within lymphoid organs than Migration properties of memory-phenotype in non-SPF parabionts similar, generalizing these results diverse infections and conditions. TRM shared overlapping transcriptional...
There is wide variation in population-level pain prevalence estimates studies of survey data around the world. The role country-level social, economic, and political contextual factors explaining this has not been adequately examined. We estimated unspecified adults aged 25+ years across 52 countries using from World Health Survey 2002 to 2004. Combining sources estimating multilevel regressions, we compared explored which explain cross-country variations prevalence, accounting for...
Acute myeloid leukemia (AML) poses a singular challenge for chimeric antigen receptor (CAR) therapy owing to its phenotypic heterogeneity and similarity normal hematopoietic stem/progenitor cells (HSPCs). Here we expound CAR strategy intended efficiently target AML while minimizing HSPC toxicity. Quantification of expression in relapsed/refractory patient samples HSPCs reveals therapeutic window gated co-targeting ADGRE2 CLEC12A: We combine an attenuated ADGRE2-CAR with CLEC12A-chimeric...
Perilipin A coats the lipid storage droplets in adipocytes and is polyphosphorylated by protein kinase (PKA); fact that PKA activates lipolysis suggests a role for perilipins this process. To assess whether participate directly PKA-mediated lipolysis, we have expressed constructs coding native mutated forms of two major splice variants perilipin gene, B, Chinese hamster ovary fibroblasts. Perilipins localize to droplet surfaces displace adipose differentiation-related normally these cells....
Abstract IL-15 regulates central and effector memory CD8 T cell (TCM TEM, respectively) homeostatic proliferation, maintenance, longevity. Consequently, availability hypothetically defines the carrying capacity for total cells within host. In conflict with this hypothesis, previous observations demonstrated that boosting generates preternaturally abundant TEM increases quantity of in mice. article, we provide a potential mechanistic explanation by reporting boosted circulating do not require...
ABSTRACT Type B influenza viruses can cause substantial morbidity and mortality in the population, vaccination remains by far best means of protection against infections with these viruses. Here, we report construction mutant for potential use as improved live-virus vaccine candidates. Employing reverse genetics, altered NS1 gene, which encodes a type I interferon (IFN) antagonist. The resulting induced IFN and, consequence, were found to be attenuated vitro vivo. absence pathogenicity...
During eukaryotic mRNA transcription, the synthetic activity and processing factor interactions of RNA polymerase II (RNAP II) are regulated by phosphorylation its carboxyl-terminal domain (CTD), with modification occurring primarily on serines 2 5 CTD. We previously showed that herpes simplex virus type 1 (HSV-1) infection rapidly triggers loss RNAP forms bearing serine (Ser-2P II). Here we show HSV-1 immediate-early (IE) protein ICP22 is responsible for this effect during IE phase...
Abstract Vaccines are desired that maintain abundant memory T cells at nonlymphoid sites of microbial exposure, where they may be anatomically positioned for immediate pathogen interception. Here, we test the impact antigen persistence on mouse CD8 and CD4 cell distribution differentiation by comparing responses to infections with different strains LCMV cause either acute or chronic infections. We used in vivo labeling techniques discriminate between present within tissues populations fail...
Background: Engineering chimeric antigen receptor natural killer cells (CAR-NK) with soluble interleukin-15 (IL-15) has been shown to enhance NK cell proliferation, proinflammatory cytokine secretion, and cytotoxic activity. While CAR-NK therapies have demonstrated safety in clinical trials, there is uncertainty the levels of circulating IL-15 that may be secreted patients due engineered on cells. The objective this work was develop a QSP modeling framework predict associated cellular...
The immune system adapts to constitutive antigens preserve self-tolerance, which is a major barrier for anti-tumor immunity. Antigen-specific reversal of tolerance constitutes goal spur therapeutic applications. Here, we show that robust, iterative, systemic stimulation targeting tissue-specific in the context acute infections reverses established CD8+ T cell self, including cells survive negative selection. This strategy results large numbers circulating and resident memory self-specific...
Previous studies have shown that herpes simplex virus type 1 (HSV-1) infection alters the phosphorylation of carboxyl-terminal domain (CTD) RNA polymerase II (RNAP II), creating a new form enzyme known as RNAP II(I). However, specific changes induced by HSV-1 not been characterized. In this study, we used phospho-specific anti-CTD antibodies to probe structure postinfection II. We find II(I) is phosphorylated on serine-5 (Ser-5) CTD consensus repeat but generally lacks serine-2 (Ser-2)....
Imprime PGG (Imprime) is an i.v. administered, yeast β-1,3/1,6 glucan in clinical development with checkpoint inhibitors. Imprime-mediated innate immune activation requires complex formation naturally occurring IgG anti-β Abs (ABA). We administered to healthy human volunteers assess the necessity of ABA for immunopharmacodynamic (IPD) changes. (4 mg/kg) was single and multiple infusions. Subsets subjects were premedicated antihistamine corticosteroid. Peripheral blood measured before, during...
Purpose: To explore the extent to which knowledge- and skill-based learning regarding social justice and/or advocacy is included in course descriptions of required courses accredited, English-speaking dietitian training programs Canada. Methods: This study a mixed-methods content analysis sampled from university academic calendars for across Results: Quantitative showed that (n = 403) few instances justice-related terminology 63). Two themes emerged qualitative analysis: competing...
Abstract Background The majority of evidence indicates that exposure to war and other traumatic events continue have negative impacts on health across the life course. However, existing research effects primarily concentrates short-term among veterans in high-income countries sent elsewhere battle. Yet, most wars situate lower- middle-income countries, where many are now or will soon be entering old age. Consequently, current burden has ignored an important global population. Methods Vietnam...