A5084685721- Cell Adhesion Molecules Research
- Monoclonal and Polyclonal Antibodies Research
- Radiopharmaceutical Chemistry and Applications
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- RNA Research and Splicing
- Histone Deacetylase Inhibitors Research
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Pancreatic and Hepatic Oncology Research
- Ferroptosis and cancer prognosis
- Cell Image Analysis Techniques
- Cancer Research and Treatments
- AI in cancer detection
- Hepatocellular Carcinoma Treatment and Prognosis
- Phagocytosis and Immune Regulation
- Cancer, Hypoxia, and Metabolism
- RNA and protein synthesis mechanisms
- Synthesis and Catalytic Reactions
- RNA Interference and Gene Delivery
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Immune Cell Function and Interaction
- 3D Printing in Biomedical Research
University of Baltimore
2022-2024
Johns Hopkins University
2021-2024
Sidney Kimmel Comprehensive Cancer Center
2021-2024
Johns Hopkins Medicine
2021-2024
Convergence
2023
Sidney Kimmel Cancer Center
2021
Bloomberg (United States)
2021
Neoadjuvant immunotherapy is thought to produce long-term remissions through induction of antitumor immune responses before removal the primary tumor. Tertiary lymphoid structures (TLS), germinal center-like that can arise within tumors, may contribute establishment immunological memory in this setting, but understanding their role remains limited. Here, we investigated contribution TLS immunity hepatocellular carcinoma (HCC) treated with neoadjuvant immunotherapy. We found induced formation...
<p>The supplementary figures file</p>
<p>The supplementary figures file</p>
Longitudinal imaging of 3D cell cultures like tumor organoids and spheroids offers crucial insights into cancer progression treatment. However, spatial displacement during time-course imaging, caused by matrix detachment or experimental artifacts, can confound analyses. Existing computational methods struggle to address this issue. We present a new algorithm evaluate data integrity rectify mislabeling in longitudinal culture. Our integrates permutation-based optimization with Procrustes...
Tumor involvement of major vascular structures limits surgical options in pancreatic adenocarcinoma (PDAC), which turn opportunities for cure. Despite advances locoregional approaches, there is currently no role incomplete resection. This study evaluated a gelatinized neoantigen-targeted vaccine applied to grossly positive resection margin preventing local recurrence. Incomplete was performed mice bearing syngeneic flank Panc02 tumors, leaving 1 mm rim adherent the muscle bed. A previously...
Abstract Background Of the only 20% of patients with resectable pancreatic ductal adenocarcinoma (rPDA), cancer recurs in 80% cases. Epigenetic dysregulation is an early hallmark cells acquiring metastatic potential, and epigenetic modulators may reactivate tumor suppressor genes, delay recurrence, sensitize PDA to future chemotherapy. Methods This was a randomized phase II study (NCT01845805) CC-486 (oral DNA methyltransferase inhibitor azacitidine) vs. observation (OBS) rPDA harboring...
Abstract Background: Aberrant alternative splicing can generate neoantigens, which themselves stimulate immune responses and surveillance. Previous methods for quantifying splicing-derived neoantigens are limited by independent references potential batch effects. Results: Here, we introduce SpliceMutr, a bioinformatics approach pipeline identifying derived from tumor normal data. SpliceMutr facilitates the identification of tumor-specific antigenic splice variants, predicts MHC-binding...
<p>The supplementary figures file</p>
<p>Comparison of predicted splicing antigens from SpliceMutr to proteomics datasets. <b>A,</b> The log<sub>10</sub>-transformed total number MHC-binding kmers found with and without reference kmer filtering in all samples the breast cancer TCGA cohort (BRCA). <b>B,</b> percentage IEAtlas-validated immunogenic between (BRCA).</p>
<p>Per splice junction normalized SA for responders compared with baseline samples. The averaged across samples the subset of junctions derived from top 20 genes highest per sample. black horizontal line is median *, <i>P</i> value ≤ 0.05; **, 0.005; ***, 0.0005; ****, 0.00005. SA, splicing antigenicity.</p>
<div>Abstract<p>Aberrant alternative splicing can generate neoantigens, which themselves stimulate immune responses and surveillance. Previous methods for quantifying splicing-derived neoantigens are limited by independent references potential batch effects. Here, we introduce SpliceMutr, a bioinformatics approach pipeline identifying from tumor normal data. SpliceMutr facilitates the identification of tumor-specific antigenic splice variants, predicts MHC-binding affinity,...
<p>Pan-cancer correlation analysis of per-sample SA with nonsilent mutations in splicing machinery coding genes. Distribution per sample, averaged across genes, by the factor gene SF3B1 BRCA (<b>A</b>) or HNSC (<b>B</b>). *, <i>P</i> value ≤ 0.05. See TCGA cancer-type abbreviations Supplementary Table S1. SA, antigenicity.</p>
<p>Per-patient SA of ICI-treated patients with melanoma per treatment arm and response type after treatment. <b>A,</b> The per-patient pseudo purity compared the mean averaged across genes by for all arms. Kendall Tau test. <b>B,</b> patient normalized purity, arms combined. Wilcoxon test Cohens <i>d</i>. ****, <i>P</i> value ≤ 0.00005. SA, splicing antigenicity.</p>
<p>SA by tissue type and in relation to the tumor mutational burden. <b>A,</b> The SA averaged across genes per sample for normal samples each analyzed (Wilcoxon test, Cohens <i>d</i>). <b>B,</b> all TMB=high TMB-low TCGA (linear regression, **, <i>P</i> value ≤ 0.005; ***, 0.0005; ****, 0.00005. See cancer-type abbreviations Supplementary Table S1. SA, splicing antigenicity.</p>
<p>SpliceMutr pipeline. The SpliceMutr pipeline uses RNA-seq data from two groups of samples and evaluates the changes in SA between them. In this example, alternative splicing analysis compares tumor normal samples. performs splicing-aware alignment, gene expression quantification, HLA genotyping. alignment splice junction counts are then input into LeafCutter to evaluate differential usage. tumor-specific normal-specific junctions undergo transcript formation, translation,...
Abstract Background: Tertiary lymphoid structures (TLS) are ectopic follicles that arise in non-lymphoid tissue. TLS may contribute to response immune checkpoint blockade (ICB) solid tumors, but understanding of the life cycle these structures, particularly circumstances their resolution and functional contribution this stage adaptive response, remains incomplete. Methods: We employed a multi-omics approach evaluate tumors patients with hepatocellular carcinoma (HCC) treated neoadjuvant ICB...
Abstract Fibrolamellar hepatocellular carcinoma (FLC) is a rare and often lethal form of liver cancer that primarily affects children young adults. A fusion between DNAJB1, heat shock chaperone protein, PRKACA, the catalytic domain protein kinase (PKA) has been identified as signature genomic event in FLC, but effect this on tumor immune microenvironment not understood. We created an orthotopic, syngeneic model FLC (TIBx-FLC) by inducing DNAJB1-PRKACA murine hepatoblastoma-derived cell line...