A5039974944- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Ferroptosis and cancer prognosis
- Cancer-related molecular mechanisms research
- Genetic factors in colorectal cancer
- Cancer Cells and Metastasis
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Single-cell and spatial transcriptomics
- Cell Adhesion Molecules Research
- Archaeology and ancient environmental studies
- T-cell and B-cell Immunology
- Molecular Biology Techniques and Applications
- Genomic variations and chromosomal abnormalities
- Tree-ring climate responses
- Archaeology and Natural History
- Renal Transplantation Outcomes and Treatments
- Defense, Military, and Policy Studies
- Renal and related cancers
- History and Developments in Astronomy
- Pacific and Southeast Asian Studies
- Viral-associated cancers and disorders
Johns Hopkins University
2019-2025
Bloomberg (United States)
2022-2025
Johns Hopkins Medicine
2023-2025
Advanced Imaging Research (United States)
2024-2025
Sidney Kimmel Comprehensive Cancer Center
2022-2024
Translational Genomics Research Institute
2017-2021
Physical Sciences (United States)
2019
Museum Of Northern Arizona
1943
Cell-free DNA (cfDNA) in urine is a promising analyte for noninvasive diagnostics. However, cfDNA highly fragmented. Whether characteristics of these fragments reflect underlying genomic architecture unknown. Here, we characterized fragmentation patterns using whole-genome sequencing. Size distribution showed multiple strong peaks between 40 and 120 base pairs (bp) with modal size 81- sharp 10-bp periodicity, suggesting transient protection from complete degradation. These properties were...
Genome-wide fragmentation patterns in cell-free DNA (cfDNA) plasma are strongly influenced by cellular origin due to variation chromatin accessibility across cell types. Such differences between healthy and cancer cells provide the opportunity for development of novel diagnostics. Here, we investigated whether analysis cfDNA fragment end positions their surrounding sequences reveals presence tumor-derived blood. We performed genome-wide from 521 samples analyzed sequencing data an additional...
Regulatory T cells (T reg ) are conventionally viewed as suppressors of endogenous and therapy-induced antitumor immunity; however, their role in modulating responses to immune checkpoint blockade (ICB) is unclear. In this study, we integrated single-cell RNA-seq/T cell receptor sequencing (TCRseq) >73,000 tumor-infiltrating (TIL-T from anti–PD-1–treated treatment-naive non–small lung cancers (NSCLC) with analysis tumor-associated antigen (TAA)–specific derived a murine tumor model. We...
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<div>AbstractPurpose:<p>Co-mutations of the <i>Kirsten rat sarcoma virus</i> (<i>KRAS</i>) and <i>serine</i>/<i>threonine kinase 11</i> (<i>STK11</i>) genes in advanced non–small cell lung cancer (NSCLC) are associated with immune checkpoint blockade (ICB) resistance. Although neoadjuvant chemoimmunotherapy is now a standard-of-care treatment for resectable NSCLC, clinical immunologic impacts <i>KRAS</i>...
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Abstract Identifying tumor-specific T cell clones that mediate immunotherapy responses remains challenging. Mutation-associated neoantigen (MANA) -specific CD8+ tumor-infiltrating lymphocytes (TIL) have been shown to express high levels of CXCL13 and CD39 ( ENTPD1 ), low IL-7 receptor IL7R ) in many cancer types, but their collective relevance functionality has not established. Here we present an integrative tool identify MANA-specific TIL using weighted expression these three genes lung...
Abstract Purpose: Co-mutations of the KRAS and STK11 genes in advanced non-small cell lung cancer (NSCLC) are associated with immune checkpoint blockade (ICB) resistance. While neoadjuvant chemoimmunotherapy is now a standard care treatment for resectable NSCLC, clinical immunologic impact andSTK11 co-mutations this setting unknown. Experimental design: We evaluated compared recurrence-free survival KRAS-mutated NSCLC tumors, or without co-occuring mutations, treated ICB. Single...
Abstract Fragmentation patterns observed in plasma DNA reflect chromatin accessibility contributing cells. Since shed from cancer cells and blood may differ fragmentation patterns, we investigated whether analysis of genomic positioning nucleotide sequence at fragment ends can reveal the presence tumor aid diagnostics. We analyzed whole genome sequencing data >2700 samples including healthy individuals patients with 11 different types. higher fractions fragments aberrantly positioned...
The tree-ring record in the Flagstaff area goes back to about 500 A.D., with one gap sequence prior 1317 A.D. To close this of forty years, a sampling was taken from Kinnikinnick ruin on Anderson Mesa twenty-two miles southeast Flagstaff. Material found there June, 1940, by Dr. A. E. Douglass, yielded dates earlier part missing period. location site postulated southern boundary Sinagua branch Mogollon made it further significance. It seems have escaped notice early investigators, is...
Abstract Cell-free DNA (cfDNA) in urine is a promising analyte for noninvasive diagnostics. However, cfDNA highly fragmented and whether characteristics of these fragments reflect underlying genomic architecture unknown. Here, we perform comprehensive characterization fragmentation patterns cfDNA. We show modal size genome-wide distribution are consistent with transient protection from degradation by stable intermediates nucleosome disassembly. Genome-wide occupancy fragment sizes...
<h3>Background</h3> We and others have shown that validated neoantigen-specific CD8+ TIL from several cancer types express high levels of <i>CXCL13</i> <i>ENTPD1</i> (CD39), low level <i>IL7R</i>. Notably, among a small number functionally tumor-reactive TIL, those ICB-resistant tumors were transcriptionally distinct. A major limitation impeding assessment this observation in larger cohort is the expensive cumbersome nature functional T cell assays detecting human TIL. therefore developed...
<h3>Background</h3> Neoadjuvant PD-1 blockade combined with chemotherapy(ICB+chemo) is now standard of care for the treatment resectable non-small cell lung cancer(NSCLC).<sup>1–4</sup> However, mechanisms underpinning its therapeutic efficacy are largely unexplored, namely if chemotherapy has an immunomodulatory role when checkpoint agents(ICB).<sup>4–6</sup> We and others have shown that CXCL13 upregulated on tumor-reactive TIL. use as a surrogate tumor specificity to better understand...
Abstract Background: Clinical response to immune checkpoint blockade (ICB) is predicated upon the existence of tumor-reactive T cells, but their precise targets remain poorly defined. Some patients with low tumor mutational burden (TMB) lung adenocarcinoma (LUAD) derive clinical benefit from ICB, suggesting that non-mutated antigens may serve as cell targets. Human endogenous retroviruses (hERVs) can be differentially expressed in malignant cells due epigenetic dysregulation and targeted by...
8523 Background: Neoadjuvant (NEO) chemotherapy (chemo) plus nivolumab (nivo) has received FDA approval for treatment of resectable NSCLC, demonstrating superior event-free survival compared to chemo alone. However, outcomes NEO ICI-based therapies in patients (pts) with oncogene-driven (OD)-NSCLC remains an unanswered question. Methods: We conducted a retrospective secondary analysis pts enrolled the clinical trial NCT02259621 stage I-IIIA treated therapies: nivo alone, nivo+ipilimumab...
<h3>Background</h3> PD-1/PD-L1 pathway blockade unleashes tumor specific T cells.<sup>1</sup> Neoantigens are the most well-studied antigens, however cells targeting neoantigens difficult to detect. Our recent integrated scTCRseq/RNAseq studies on neoantigen-specific TILs in lung cancer illustrated a nearly uniform transcriptional program characterized by high expression of CXCL13 and ENTPD1 (CD39), low IL7R.<sup>2</sup> We therefore hypothesized that comprehensive profile TIL could be...