A5020686003- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Glioma Diagnosis and Treatment
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Ferroptosis and cancer prognosis
- Meningioma and schwannoma management
- T-cell and B-cell Immunology
- Single-cell and spatial transcriptomics
- Neuroinflammation and Neurodegeneration Mechanisms
- Immunotherapy and Immune Responses
- interferon and immune responses
- Mathematical Biology Tumor Growth
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Extracellular vesicles in disease
- Bacterial Genetics and Biotechnology
- Acute Myeloid Leukemia Research
- Galectins and Cancer Biology
- Gene Regulatory Network Analysis
- Virus-based gene therapy research
- Immune cells in cancer
- Protein Tyrosine Phosphatases
- DNA and Nucleic Acid Chemistry
- Eosinophilic Disorders and Syndromes
Washington University in St. Louis
2021-2024
Massachusetts General Hospital
2022-2024
Harvard University
2023-2024
Neurological Surgery
2021-2023
Rice University
2019
Baylor College of Medicine
2018
Recent investigations of the meninges have highlighted importance dura layer in central nervous system immune surveillance beyond a purely structural role. However, our understanding largely stems from use pre-clinical models rather than human samples.
Recent clinical trials have highlighted the limited efficacy of T cell-based immunotherapy in patients with glioblastoma (GBM). To better understand characteristics tumor-infiltrating lymphocytes (TIL) GBM, we performed cellular indexing transcriptomes and epitopes by sequencing single-cell RNA paired V(D)J sequencing, respectively, on TILs from two cohorts totaling 15 high-grade glioma, including GBM or astrocytoma, IDH-mutant, grade 4 (G4A). Analysis CD8+ TIL landscape reveals an...
Abstract Despite some success in secondary brain metastases, targeted or immune-based therapies have shown limited efficacy against primary malignancies such as glioblastoma (GBM). Although the intratumoral heterogeneity of GBM is implicated treatment resistance, it remains unclear whether this diversity observed within metastases and to what extent cancer cell–intrinsic sculpts local immune microenvironment. Here, we profiled immunogenomic state 93 spatially distinct regions from 30...
The central nervous system (CNS) antigen-presenting cell (APC) that primes antitumor CD8+ T-cell responses remains undefined. Elsewhere in the body, conventional dendritic 1 (cDC1) performs this role. However, steady-state brain parenchyma cDC1 are extremely rare; cDCs localize to choroid plexus and dura. Thus, whether play a function presenting antigen derived from parenchymal sources tumor setting unknown. Using preclinical glioblastoma (GBM) models cDC1-deficient mice, we explored...
Treatment resistance in glioblastoma (GBM) is largely driven by the extensive multi-level heterogeneity that typifies this disease. Despite significant progress toward elucidating GBM's genomic and transcriptional heterogeneity, a critical knowledge gap remains defining at spatial level. To address this, we employed transcriptomics to map architecture of GBM ecosystem. This revealed tumor cell states are jointly defined gene expression localization, multicellular niches whose composition...
Adoptive cellular therapies with chimeric antigen receptor T cells have revolutionized the treatment of some malignancies but shown limited efficacy in solid tumors such as glioblastoma and face a scarcity safe therapeutic targets. As an alternative, cell (TCR)-engineered therapy against tumor-specific neoantigens has generated significant excitement, there exist no preclinical systems to rigorously model this approach glioblastoma.
The N protein of phage Mu was indicated from studies in Escherichia coli to hold linear chromosomes a circular conformation by non-covalent association, and thus suggested potentially bind DNA double-stranded ends. Because its role association with DNA, we tested whether fluorescent-protein fusions might provide useful tool for labeling damage including double-strand break (DSB) ends single cells. We compared N-GFP biochemically well documented DSB-end binding protein, the Gam Mu, also fused...
Abstract Chronic myeloproliferative neoplasms (MPNs) exhibit a propensity for transformation to secondary acute myeloid leukemia (sAML), which the underlying mechanisms remain poorly understood, resulting in limited treatment options and dismal clinical outcomes. Here, we performed bulk transcriptome profiling accompanied by single cell RNA-sequencing on CD34+ stem/progenitor cells from serial patient samples obtained at chronic MPN sAML phases, identified aberrantly increased expression of...
Abstract Recent investigation of the meninges, specifically dura layer, has highlighted its importance in CNS immune surveillance beyond a purely structural role. However, most our understanding meninges stems from use pre-clinical models rather than human samples. In this study, we single cell RNA-sequencing to perform first characterization both non-tumor-associated and meningioma First, reveal complex microenvironment that is transcriptionally distinct meningioma. addition, through T...
<p>Gene markers for Xenium in situ cell type identification.</p>
<p>Heatmap of top differentially expressed genes by CD8+ T cell states from cohorts 1 and 2.</p>
<p>scGSEA correlation values</p>
<p>Dot plot of select gene markers for cell type identification CD8+ T cells from cohort 1.</p>
<p>Comparison of CD8+ GZMK+ TIL from IDH-WT GBM and IDH-mut G4A samples.</p>
<p>Antibody markers and respective clone numbers.</p>
<p>Patient demographics and sample characteristics.</p>
<p>Comparison of TIL from primary and recurrent GBM samples.</p>
<p>Harmony integration of TIL from many cancer types.</p>
<p>Inhibitory score analysis of the integrated T cells from cohorts 1 and 2.</p>
<p>Gene markers for cell type identification and gene signatures.</p>
<p>MAIT clonotype occurrence in T cells from cohort 1.</p>
<p>Analysis of RNA Tirosh exhaustion and inhibitory scores expressed by T cells from cohort 1.</p>
<p>Neighborhood enrichment raw z scores</p>