Stephen O’Flanagan

ORCID: 0000-0002-9286-1208
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About
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Research Areas
  • Immune Cell Function and Interaction
  • T-cell and B-cell Immunology
  • Cancer Immunotherapy and Biomarkers
  • CAR-T cell therapy research
  • Immunotherapy and Immune Responses
  • Adenosine and Purinergic Signaling
  • Microbial Inactivation Methods
  • Single-cell and spatial transcriptomics
  • SARS-CoV-2 and COVID-19 Research
  • Phagocytosis and Immune Regulation
  • COVID-19 Clinical Research Studies
  • Immune responses and vaccinations
  • Plasma Applications and Diagnostics
  • Virus-based gene therapy research
  • RNA Interference and Gene Delivery
  • Microfluidic and Bio-sensing Technologies
  • Reproductive System and Pregnancy
  • Electrostatic Discharge in Electronics
  • Immune Response and Inflammation
  • Cancer, Stress, Anesthesia, and Immune Response
  • Immune cells in cancer
  • vaccines and immunoinformatics approaches
  • Influenza Virus Research Studies
  • Diabetes and associated disorders

University of Minnesota
2019-2025

University of Minnesota Medical Center
2019-2024

Minot State University
2021

University of Minnesota System
2019

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing Abs target receptor binding domain of spike (S) protein, a focus successful vaccine efforts. Concerns have arisen that S-specific immunity may fail to neutralize emerging variants. We show vaccination with human adenovirus type 5 vector expressing SARS-CoV-2 nucleocapsid (N) protein can establish protective immunity, defined by reduced weight loss and viral load, in both Syrian...

10.4049/jimmunol.2100421 article EN The Journal of Immunology 2021-06-30

Focal thermal therapy (Heat), cryosurgery (Cryo) and irreversible electroporation (IRE) are increasingly used to treat cancer. However, local recurrence systemic spread persistent negative outcomes. Nevertheless, emerging work with immunotherapies (i.e., checkpoint blockade or dendritic cell (DC) vaccination) in concert focal therapies may improve To understand the role of priming immune system for immunotherapy, an vitro model T response after exposure B16 melanoma lysates lethal exposures...

10.1080/02656736.2018.1539253 article EN cc-by International Journal of Hyperthermia 2019-01-01

Memory CD8+ T cells populate non-lymphoid tissues (NLTs) following pathogen infection, but little is known about the establishment of endogenous tumor-specific tissue-resident memory (T

10.1038/s41467-021-24132-6 article EN cc-by Nature Communications 2021-06-23

Abstract The magnitude of SARS-CoV-2–specific T cell responses correlates inversely with human disease severity, suggesting involvement in primary control. Whereas many COVID-19 vaccines focus on establishing humoral immunity to viral spike protein, vaccine-elicited may bolster durable protection or cross-reactivity variants. To better enable mechanistic and vaccination studies mice, we identified a dominant CD8 SARS-CoV-2 nucleoprotein epitope. Infection ACE2 transgenic mice elicited robust...

10.4049/jimmunol.2001400 article EN The Journal of Immunology 2021-01-13

Abstract Expression of the purinergic receptor P2RX7 by CD8+ T cells promotes generation memory populations following acute infections. However, data suggest that may limit efficacy antitumor responses. Herein, we show is beneficial for optimal melanoma control in a mouse T-cell adoptive transfer model. Tumor-specific P2rx7–/– exhibited impaired mitochondrial maintenance and function but did not display signs overt exhaustion early response. as tumor burden increased, relative frequency...

10.1158/2326-6066.cir-21-0691 article EN Cancer Immunology Research 2022-05-19

Humans experience frequent respiratory infections. Immunology and vaccinology studies in mice are typically performed naive specific pathogen-free animals responding to their very first challenge. We found that the infection induces lifelong enlargement of lung-draining mediastinal lymph nodes (medLNs). Furthermore, infection-experienced medLNs supported better T cell surveillance effector responses new unrelated infections exhibited more biased accumulation memory establishment within lung....

10.4049/jimmunol.2400010 article EN The Journal of Immunology 2024-04-15

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing antibodies target receptor binding domain of spike (S) protein, a focus successful vaccine efforts. Concerns have arisen that S-specific immunity may fail to neutralize emerging variants. We show vaccination with HAd5 expressing nucleocapsid (N) protein can establish protective immunity, defined by reduced weight loss and viral load, in both Syrian hamsters k18-hACE2...

10.1101/2021.04.26.441518 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2021-04-27

Self-specific CD8 + T cells can escape clonal deletion, but the properties and capabilities of such in a physiological setting are unclear. We characterized polyclonal specific for melanocyte antigen tyrosinase-related protein 2 (Trp2) mice expressing or lacking this enzyme (due to deficiency Dct , which encodes Trp2). Phenotypic gene expression profiles pre-immune Trp2/K b -specific were similar; size population was only slightly reduced wild-type (WT) compared -deficient ( -/- ) mice....

10.7554/elife.65615 article EN public-domain eLife 2021-04-30

Abstract Respiratory tract resident memory T cells (Trm), typically generated by local vaccination or infection, can accelerate control of pulmonary infections that evade neutralizing antibody. It is unknown whether mRNA establishes respiratory Trm. We a self-amplifying vaccine encoding the influenza A virus nucleoprotein encapsulated in modified dendron-based nanoparticles. Here we report how routes immunization mice, including contralateral versus ipsilateral intramuscular boosts,...

10.1101/2022.06.02.494574 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2022-06-02

Abstract In contrast to naive T cells, memory cells do not require TCR stimulation survive and are maintained by cytokines undergo homeostatic proliferation. However, permanent of persistent antigen in chronic infections cancer causes a dysfunctional state, termed cell exhaustion (TEX). Yet, how signaling influences the location, maintenance, function subsets remains incompletely understood. Using an inducible knockout model (UBC-CreERT2 x Trac flox/flox), longevity tissue resident (TRM)...

10.4049/jimmunol.212.supp.1229.5286 article EN The Journal of Immunology 2024-05-01

Abstract Autoimmune diseases afflict >20M Americans and alarmingly the incidence of autoimmune is increasing particularly in children. The hygiene hypothesis (HH) proposes that there an inverse correlation between microbial exposure subsequent development autoimmunity, i.e., “cleaner” environment, higher probability autoimmunity develops. Critically, how exposures infections alter self-antigen (Ag), a critical component immune tolerance, unknown. Our data show immune-experienced mice...

10.4049/jimmunol.212.supp.1116.4418 article EN The Journal of Immunology 2024-05-01

<div>Abstract<p>Expression of the purinergic receptor P2RX7 by CD8<sup>+</sup> T cells promotes generation memory populations following acute infections. However, data suggest that may limit efficacy antitumor responses. Herein, we show is beneficial for optimal melanoma control in a mouse T-cell adoptive transfer model. Tumor-specific <i>P2rx7<sup>–/–</sup></i> exhibited impaired mitochondrial maintenance and function but did not display signs...

10.1158/2326-6066.c.6550745.v1 preprint EN 2023-04-04

<div>Abstract<p>Expression of the purinergic receptor P2RX7 by CD8<sup>+</sup> T cells promotes generation memory populations following acute infections. However, data suggest that may limit efficacy antitumor responses. Herein, we show is beneficial for optimal melanoma control in a mouse T-cell adoptive transfer model. Tumor-specific <i>P2rx7<sup>–/–</sup></i> exhibited impaired mitochondrial maintenance and function but did not display signs...

10.1158/2326-6066.c.6550745 preprint EN 2023-04-04

Abstract Resident memory T cells (TRM) constitute a recently identified lymphocyte lineage that occupies non-lymphoid tissues (NLT) without recirculating. In murine models, upon antigenic rechallenge, TRM trigger antiviral responses in neighboring innate and adaptive immune cells, recruit effectors from circulation. Collectively this is referred to as ‘sensing alarm’ function. However, the full range of functions has not been assessed, non-human primate/human function remains almost entirely...

10.4049/jimmunol.210.supp.69.02 article EN The Journal of Immunology 2023-05-01

Abstract For sixty years we have understood that lymphocytes recirculate through blood and secondary lymphoid organs (SLO). Recently, it has been observed SLOs contain resident populations of memory T cells. Here, show conventional isolation techniques grossly underestimate the proportion SLO CD8+ RM,and cells constitute a substantial fraction regionalized immunity within LNs. We found RMare very long-lived in mice persist for >500 days after single infection with LCMV Armstrong....

10.4049/jimmunol.210.supp.218.23 article EN The Journal of Immunology 2023-05-01
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