A5083850882- Viral Infections and Vectors
- interferon and immune responses
- Mosquito-borne diseases and control
- Cancer-related gene regulation
- Connective tissue disorders research
- Immune Response and Inflammation
- vaccines and immunoinformatics approaches
- Respiratory viral infections research
- Signaling Pathways in Disease
- Inflammasome and immune disorders
- Endoplasmic Reticulum Stress and Disease
- Wnt/β-catenin signaling in development and cancer
- Cytokine Signaling Pathways and Interactions
- Cytomegalovirus and herpesvirus research
- Bone and Dental Protein Studies
- Cardiomyopathy and Myosin Studies
- Toxoplasma gondii Research Studies
- Viral Infections and Outbreaks Research
Oregon Health & Science University
2017-2025
Shriners Hospitals for Children - Portland
2019-2021
Vaccine and Gene Therapy Institute
2020
Gene Therapy Laboratory
2020
The type I interferon (IFN) system represents an essential innate immune response that renders cells resistant to virus growth via the molecular actions of IFN-induced effector proteins. IFN-mediated cellular states inhibit numerous and diverse types, including those known pathogenicity as well potentially emerging agents. As such, targeted pharmacologic activation IFN may represent a novel therapeutic strategy prevent infection or spread clinically impactful viruses. In light this, we...
Pharmacologic activation of the innate immune response is being actively pursued for numerous clinical purposes including enhancement vaccine potency and potentiation anti-cancer immunotherapy. Pattern recognition receptors (PRRs) represent especially useful targets these efforts as their engagement by agonists can trigger signaling pathways that associate with phenotypes desirable specific outcomes. Stimulator interferon genes (STING) an ER-resident PRR reactive to cyclic dinucleotides such...
Secretion of interleukin-1β (IL-1β) represents a fundamental innate immune response to microbial infection that, at the molecular level, occurs following activation proteolytic caspases that cleave immature protein into secretable form. Human cytomegalovirus (HCMV) is archetypal betaherpesvirus invariably capable lifelong through activity numerous virally encoded evasion phenotypes. Innate pathways responsive cytoplasmic double-stranded DNA (dsDNA) are known be activated in contact between...
Collagen is the most abundant protein in humans. It has a characteristic triple-helix structure and heavily posttranslationally modified. The complex biosynthesis of collagen involves processing by many enzymes chaperones rough endoplasmic reticulum. Lysyl hydroxylase 1 (LH1) required to hydroxylate lysine for cross-linking carbohydrate attachment within triple helical sequences. Additionally, recent study prolyl 3-hydroxylase 3 (P3H3) demonstrated that this enzyme may be critical LH1...
Mayaro virus (MAYV) is a mosquito-transmitted alphavirus that causes debilitating and persistent arthritogenic disease. While MAYV was previously reported to infect non-human primates (NHP), characterization of pathogenesis currently lacking. Therefore, in this study we characterized infection immunity rhesus macaques. To inform the selection viral strain for NHP experiments, evaluated five strains C57BL/6 mice showed BeAr505411 induced robust tissue dissemination Three male macaques were...
The innate immune response to cytosolic DNA involves transcriptional activation of type I interferons (IFN-I) and proinflammatory cytokines. This represents the culmination intracellular signaling pathways that are initiated by pattern recognition receptors engage require adaptor protein Stimulator Interferon Genes (STING). These responses lead generation cellular tissue states impair microbial replication facilitate establishment long-lived, antigen-specific adaptive immunity. Ultimately...
Mutations in the FKBP14 gene encoding FKBP22 (FK506 Binding Protein 22 kDa) cause kyphoscoliotic Ehlers-Danlos Syndrome (kEDS). The first clinical report showed that a lack of protein due to mutations causing nonsense-mediated decay mRNA leads wide spectrum phenotypes including progressive kyphoscoliosis, joint hypermobility, hypotonia, hyperelastic skin, hearing loss and aortic rupture. Our previous work these phenotypic features could be correlated with functions FKBP22, which...
Abstract Vaccines comprised of inert antigen are very safe, yet they typically only weakly immunogenic and thus require co-administration factors such as adjuvants that enhance immunostimulation. Unfortunately, few approved for clinical use the mechanistic bases their function poorly understood. Stimulator Interferon Genes (STING) is PRR senses intracellular cyclic dinucleotides (CDN) synthesized by enzyme cGAS following its sensing cytosolic DNA. Numerous molecules have been identified...
Abstract Collagen is the most abundant protein in humans and heavily post-translationally modified. Its biosynthesis very complex requires three different types of hydroxylation (two for proline one lysine) that are generated rough endoplasmic reticulum (rER). These processes involve many enzymes chaperones which were collectively termed molecular ensemble collagen biosynthesis. However, function some proteins this controversial. While prolyl 3-hydroxylase 1 2 (P3H1, P3H2) bona fide...
Abstract STING is a PRR for cyclic dinucleotides (CDN) synthesized by the cytosolic enzyme cGAS following exposure to microbial or cellular DNA. This stimulates innate responses characterized localized type I IFN and proinflammatory cytokines. It thus key establishing adaptive immunity facilitating APC recruitment function. As such, an attractive target direct adjuvants anti-tumor drugs. However, also drives processes such as apoptosis autophagy that are certain shape immune responsiveness....