Project description:We developed three different protein arrays to measure IgG autoantibodies associated with Connective Tissue Diseases (CTDs), Anti-Cytokine Antibodies (ACA), and anti-viral antibody responses in 147 hospitalized COVID-19 patients in three different centers.
Project description:Influenza B virus (IBV) is considered a major respiratory pathogen responsible for seasonal respiratory disease in humans, particularly severe in children and the elderly. Seasonal influenza vaccination is considered the most efficient strategy to prevent and control IBV infections. Live attenuated influenza virus vaccines (LAIVs) are thought to induce both humoral and cellular immune responses by mimicking a natural infection, but their effectiveness have recently come into question. Thus, the opportunity exists to find alternative approaches to improve overall influenza vaccine effectiveness. Two alternative IBV backbones were developed with re-arranged genomes, re-arranged M (FluB-RAM) and a re-arranged NS (FluB-RANS). Both re-arranged viruses showed temperature sensitivity in vitro compared to the WT type B/Bris strain, were genetically stable over multiple passages in embryonated chicken eggs and were attenuated in vivo in mice. In a prime-boost regime in naïve mice, both re-arranged viruses induced antibodies against HA with hemagglutination inhibition titers considered of protective value. In addition, antibodies against NA and NP were readily detected with potential protective value. Upon lethal IBV challenge, mice previously vaccinated with either FluB-RAM or FluB-RANS were completely protected against clinical disease and mortality. In conclusion, genome re-arrangement renders efficacious LAIV candidates to protect mice against IBV.
Project description:Recent work has bolstered the possibility that peripheral changes may be relevant to Alzheimer’s disease pathogenesis in the brain. While age-associated blood-borne proteins have been targeted to restore function to the aged brain, it remains unclear whether other dysfunctional systemic states can be exploited for similar benefits. Here we investigate whether APOE allelic variation or presence of brain amyloid are associated with plasma proteomic changes and the molecular processes associated with these changes. Using the SOMAscan assay, we measured 1,305 plasma proteins from 53 homozygous, APOE3 and APOE4 subjects without dementia. We investigated the relationship of either the APOE-ε4 allele or amyloid positivity with plasma proteome changes by linear mixed effects modeling and ontology-based pathway and module trait correlation analyses. APOE4 is associated with plasma protein differences linked to atherosclerosis, tyrosine kinase activity, cholesterol transport, extracellular matrix, and synaptogenesis pathways. Independent of APOE4, we found that subjects likely harboring brain amyloid exhibit plasma proteome signatures associated with AD-linked pathways, including neurovascular dysfunction. Our results indicate that APOE4 status or presence of brain amyloid are associated with plasma proteomic shifts prior to the onset of symptoms, suggesting that systemic pathways in certain risk contexts may be plausible targets for disease modification.
Project description:Aberrant secretion of cytokines contributes to pathogenesis of leukemia and is considered a prognostic signature for recurrence of AML. We asked whether molecular targeting of TIFA can perturb NF-κB-dependent secretion of leukemic cytokines and attain better therapeutic efficacy. We performed cytokine antibody array to profile cytokines secreted by U937 cells in response to TIFA dominant-negative fragments and cytarabine treatment.
Project description:To directly test whether inhibition of IL-18 by IL-18 neutralizing monoclonal antibodies (IL-18 nAbs) is sufficient for blocking the inflammatory responses of heart caused by acute β-adrenergic insult, mice were subjected to intraperitoneal injection with rat IL-18 nAbs or IgG as a negative control 1hr after isoproterenol treatment.
Project description:Purpose: There is evidence that therapeutic cancer vaccines can lengthen survival for some cancer patients, but responses vary widely from one person to another. Methods to predict clinical outcomes will advance the field and provide new insights into critical determinants of in vivo efficacy. This study uses a high-throughput glycan microarray to assess correlations between a subject's overall survival after receiving PROSTVAC-VF and his anti-glycan humoral responses occuring in the first months after treatment with PROSTVAC-VF. Results: Humoral responses to the terminal Forssman disaccharide (Fsdi) were found to have a statistically significant correlation with survival. Long-term survival was approximately doubled in subjects with four-fold or larger anti-Fsdi responses relative to subjects with little or no anti-Fsdi response. This survival correlation was specific to vaccine treatment, as no correlation was observed in control patients immunized with wild-type poxviruses lacking the key tumor antigen, prostate specific antigen (PSA). Moreover, anti-Fsdi humoral responses were not correlated with general measures of disease severity, such as PSA levels, Gleason score, or Halabi predicted survival. Conclusion: In addition to reporting a new biomarker for monitoring benefical responses to PROSTVAC-VF, this study highlights the potential of glycan microarray technology for personalized medicine.
Project description:To determine the biological effects of MPS1 inhibition (both by siRNA and Drug (NMSP715)) on signaling pathways in GBM cells (U251 &U87), we profiled the modulation of phosphorylated and non-phosphorylated proteins using RPPA