Publications by authors named "Luke Bugada"

Article Synopsis
  • Palmoplantar pustulosis (PPP), palmoplantar psoriasis (palmPP), and dyshidrotic palmoplantar eczema (DPE) are inflammatory skin conditions that can be difficult to distinguish from one another due to similar clinical presentations.
  • Recent RNA sequencing studies of these conditions revealed overlapping inflammatory responses, particularly involving proinflammatory cytokines and immune processes, alongside unique features for each disease.
  • The findings suggest that current classifications based on clinical symptoms may be insufficient, emphasizing the need for a better molecular understanding of these diseases to improve diagnosis and treatment.
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Influenza poses a persistent health burden worldwide. To design equitable vaccines effective across all demographics, it is essential to better understand how host factors such as genetic background and aging affect the single-cell immune landscape of influenza infection. Cytometry by time-of-flight (CyTOF) represents a promising technique in this pursuit, but interpreting its large, high-dimensional data remains difficult.

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Current cancer vaccines using T cell epitopes activate antitumor T cell immunity through dendritic cell/macrophage-mediated antigen presentation, but they lack the ability to promote B/CD4 T cell crosstalk, limiting their anticancer efficacy. We developed antigen-clustered nanovaccine (ACNVax) to achieve long-term tumor remission by promoting B/CD4 T cell crosstalk. The topographic features of ACNVax were achieved using an iron nanoparticle core attached with an optimal number of gold nanoparticles, where the clusters of HER2 B/CD4 T cell epitopes were conjugated on the gold surface with an optimal intercluster distance of 5-10 nm.

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CD4 T cells play a vital role in the immune response, and their function requires T cell receptor (TCR) recognition of peptide epitopes presented in complex with MHC class II (MHCII) molecules. Consequently, rapidly identifying peptides that bind MHCII is critical to understanding and treating infectious disease, cancer, autoimmunity, allergy, and transplant rejection. Computational methods provide a fast, ultrahigh-throughput approach to predict MHCII-binding peptides but lack the accuracy of experimental methods.

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Article Synopsis
  • Researchers combined an albumin nanoparticle (Nano-PI) that carries immunomodulators with α-PD1 therapy to target the tumor's immunosuppressive environment, focusing on both lymph nodes and tumors.
  • In mouse models of breast cancer, this combination not only led to long-term tumor remission and eliminated lung metastases but also successfully repolarized M2 macrophages to M1, enhancing immune response.
  • The study indicates that Nano-PI enhances drug delivery and immune cell activity, suggesting its potential as a promising approach for future clinical trials in treating metastatic breast cancer.
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Despite promising developments in computational tools, peptide-class II MHC (MHCII) binding predictors continue to lag behind their peptide-class I MHC counterparts. Consequently, peptide-MHCII binding is often evaluated experimentally using competitive binding assays, which tend to sacrifice throughput for quantitative binding detail. Here, we developed a high-throughput semiquantitative peptide-MHCII screening strategy termed microsphere-assisted peptide screening (MAPS) that aims to balance the accuracy of competitive binding assays with the throughput of computational tools.

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Cooperative enzyme catalysis in nature has long inspired the application of engineered multi-enzyme assemblies for industrial biocatalysis. Despite considerable interest, efforts to harness the activity of cell-surface displayed multi-enzyme assemblies have been based on trial and error rather than rational design due to a lack of quantitative tools. In this study, we developed a quantitative approach to whole-cell biocatalyst characterization enabling a comprehensive study of how yeast-surface displayed multi-enzyme assemblies form.

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