A5058213730- interferon and immune responses
- Influenza Virus Research Studies
- Pancreatic and Hepatic Oncology Research
- Cancer, Hypoxia, and Metabolism
- Inflammasome and immune disorders
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Pancreatic function and diabetes
- Viral Infections and Immunology Research
- Viral Infections and Vectors
- Cancer Cells and Metastasis
- Biochemical and Molecular Research
- Melanoma and MAPK Pathways
- Long-Term Effects of COVID-19
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Heme Oxygenase-1 and Carbon Monoxide
- IL-33, ST2, and ILC Pathways
- Immune Cell Function and Interaction
- Viral gastroenteritis research and epidemiology
- Eosinophilic Esophagitis
- Colorectal Cancer Treatments and Studies
- Ferroptosis and cancer prognosis
- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
The Ohio State University
2021-2025
Columbus Oncology and Hematology Associates
2023
Roswell Park Comprehensive Cancer Center
2020-2022
Abstract A hallmark of pancreatic ductal adenocarcinoma (PDAC) is an exuberant stroma comprised diverse cell types that enable or suppress tumor progression. Here, we explored the role oncogenic KRAS in protumorigenic signaling interactions between cancer cells and host cells. We show mutation (KRAS*) drives cell-autonomous expression type I cytokine receptor complexes (IL2rγ–IL4rα IL2rγ–IL13rα1) turn are capable receiving growth signals (IL4 IL13) provided by invading Th2 microenvironment....
Significance We report the discovery of fundamental roles for noncanonical inflammasome molecule Caspase-4/11 in promoting pathological inflammatory and prothrombotic pathways severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) infections. Our work demonstrates that Caspase-11 has a broader role immune responses beyond its previously appreciated effects bacterial Further, we show Caspase-11–deficient mice infected with SARS–CoV-2 fare significantly better terms overall illness, lung...
Abstract Influenza virus activates cellular inflammasome pathways, which can be both beneficial and detrimental to infection outcomes. Here, we investigate the function of inflammasome-activated, pore-forming protein gasdermin D (GSDMD) during infection. Ablation GSDMD in knockout (KO) mice ( Gsdmd −/− ) significantly attenuates influenza virus-induced weight loss, lung dysfunction, histopathology, mortality compared with wild type (WT) mice, despite similar viral loads. Infected exhibit...
ABSTRACT Here we investigated whether interferon induced transmembrane protein 3 (IFITM3), a key antiviral deficient in certain human populations, affects interspecies adaptation of SARS-CoV-2. We found that SARS-CoV-2 Beta and Omicron variants passaged through IFITM3-deficient versus wild type mice exhibit enhanced replication pathogenesis this new host species. Enhancements associated with amino acid substitutions the viral genome, suggesting IFITM3 limits accumulation adaptive mutations....
Cardiac dysfunction is a common complication of severe influenza virus infection, but whether this occurs due to direct infection cardiac tissue or indirectly through systemic lung inflammation remains unclear. To test the etiology aspect disease, we generated novel recombinant heart-attenuated via genome incorporation target sequences for miRNAs expressed in cardiomyocytes. Compared with control virus, mice infected miR-targeted had significantly reduced heart viral titers, confirming...
Vaccines against SARS-CoV-2 that induce mucosal immunity capable of preventing infection and disease remain urgently needed. In this study, we demonstrate the efficacy Bordetella colonization factor A (BcfA), a novel bacteria-derived protein adjuvant, in spike-based prime-pull immunizations. We show i.m. priming mice with an aluminum hydroxide- BcfA-adjuvanted spike subunit vaccine, followed by booster, generated Th17-polarized CD4+ tissue-resident memory T cells neutralizing Abs....
Optimization of protective immune responses against SARS-CoV-2 remains an urgent worldwide priority. In this regard, type III IFN (IFN-λ) restricts infection in vitro, and treatment with IFN-λ limits infection, inflammation, pathogenesis murine models. Furthermore, has been developed for clinical use to limit COVID-19 severity. However, whether endogenous signaling effect on antiviral immunity long-term protection vivo is unknown. study, we identified a requirement promoting viral clearance...
Abstract SARS-CoV-2 is a worldwide health concern, and new treatment strategies are needed 1 . Targeting inflammatory innate immunity pathways holds therapeutic promise, but effective molecular targets remain elusive. Here, we show that human caspase-4 (CASP4), its mouse homologue, caspase-11 (CASP11), upregulated in infections, CASP4 expression correlates with severity of infection humans. SARS-CoV-2-infected Casp11 -/- mice were protected from severe weight loss lung pathology, including...
ABSTRACT Type III interferons (IFNλ) are innate immune cytokines that limit viral replication and coordinate tissue repair through the induction of interferon stimulated genes (ISGs). This response must be tightly regulated to avoid excessive responses result in disruption barrier integrity or inefficient allow for pathogen escape. Here we examine contribution Mitogen Activated Protein Kinase (MAPK) signaling on IFNλ-mediated antiviral activity. We find extracellular-signal-regulated kinase...
<div>Abstract<p>A hallmark of pancreatic ductal adenocarcinoma (PDAC) is an exuberant stroma comprised diverse cell types that enable or suppress tumor progression. Here, we explored the role oncogenic KRAS in protumorigenic signaling interactions between cancer cells and host cells. We show mutation (KRAS*) drives cell-autonomous expression type I cytokine receptor complexes (IL2rγ–IL4rα IL2rγ–IL13rα1) turn are capable receiving growth signals (IL4 IL13) provided by invading Th2...
Influenza virus pandemics are caused by viruses from animal reservoirs that adapt to efficiently infect and replicate in human hosts. Here, we investigated whether Interferon-Induced Transmembrane Protein 3 (IFITM3), a host antiviral factor with known deficiencies, plays role interspecies infection adaptation. We found IFITM3-deficient mice cells could be infected low doses of avian influenza failed WT counterparts, identifying new for IFITM3 controlling the minimum infectious viral dose...
<p>Supplementary Figures 1-6</p>
<p>Supplementary Figures 1-6</p>
<div>Abstract<p>A hallmark of pancreatic ductal adenocarcinoma (PDAC) is an exuberant stroma comprised diverse cell types that enable or suppress tumor progression. Here, we explored the role oncogenic KRAS in protumorigenic signaling interactions between cancer cells and host cells. We show mutation (KRAS*) drives cell-autonomous expression type I cytokine receptor complexes (IL2rγ–IL4rα IL2rγ–IL13rα1) turn are capable receiving growth signals (IL4 IL13) provided by invading Th2...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease that remains largely incurable. Although the cause for this profound therapeutic resistance poorly understood, it however partly blamed on signaling factors present in tumor microenvironment (TME), which supports proliferation and survival of neoplastic cells. Apart from being stroma rich, PDAC TME associated with a distinctive immune infiltrate. Paradoxically, most immunotherapy trials using checkpoint inhibitors,...
Abstract Cardiac dysfunction is a common extrapulmonary complication of severe influenza virus infection. Prevailing models propose that influenza-associated heart indirectly triggered by cytokine mediated cardiotoxicity downstream the inflamed lung, rather than direct infection cardiac tissue. To test etiology resulting from infection, we generated novel recombinant H1N1 A was attenuated in cardiomyocytes incorporation target sequences for miRNAs expressed specifically cell type (miR133b...