Biology subjects

Osbun, J. W.

Publications and source records attributed to Osbun, J. W..

4 recordsLinked to original sources

bioRxiv2025

Single-Cell Analysis of Meningiomas Reveals Mutation-Associated Tumor and Immune Cell Gene Expression Programs

Genomic and epigenetic profiling, particularly DNA methylation analysis, have refined the molecular classification of meningiomas and revealed marked intratumoral heterogeneity. To further characterize heterogeneity within and between patients, we analyzed meningiomas using single-cell RNA sequencing (n=11), whole-exome sequencing (n=9), and spatial transcriptomics (n=3). Single-cell analysis revealed six transcriptionally distinct tumor cell states that corresponded to unique biological processes. Integration of the single-cell data with published exome and bulk RNA sequencing data from a large cohort revealed significant associations among somatic variants, tumor cell states, and immunological signatures. Notably, NF2-altered tumors were enriched for an epithelial-to-mesenchymal transition (EMT) cell state and immune cells, whereas NF2-intact tumors were enriched for a sterol metabolism cell state. Spatial transcriptomic analysis confirmed co-localization of immune cells and EMT tumor cells. Comparisons with immune cells from other brain tumors and peripheral tissues highlighted immunological cell states specific to meningioma. Collectively, these findings refine our genetic and molecular understanding of meningioma heterogeneity and underscore the link between genotype and molecular phenotype.

cancer biology↗

bioRxiv2023

Stability of navigation in catheter-based endovascular procedures

Endovascular procedures provide surgeons and other interventionalists with minimally invasive methods to treat vascular diseases by passing guidewires, catheters, sheaths and treatment devices into the vasculature to and navigate toward a treatment site. The efficiency of this navigation affects patient outcomes, but is frequently compromised by catheter "herniation", in which the catheter-guidewire system bulges out from the intended endovascular pathway so that the interventionalist can no longer advance it. Here, we showed herniation to be a bifurcation phenomenon that can be predicted and controlled using mechanical characterizations of catheter-guidewire systems and patientspecific clinical imaging. We demonstrated our approach in laboratory models and, retrospectively, in patients who underwent procedures involving transradial neurovascular procedures with an endovascular pathway from the wrist, up in the arm, around the aortic arch, and into the neurovasculature. Our analyses identified a mathematical navigation stability criterion that predicted herniation in all of these settings. Results show that herniation can be predicted through bifurcation analysis, and provide a framework for selecting catheter-guidewire systems to avoid herniation in specific patient anatomy.

bioengineering↗

bioRxiv2022

Single-cell multi-omic analysis of the vestibular schwannoma ecosystem uncovers a nerve injury-like state

Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to the pathogenesis of these tumors remains poorly understood. We performed scRNA-seq on 15 VS samples, with paired scATAC-seq in six samples. We identified diverse Schwann cell (SC), stromal, and immune populations in the VS TME and found that repair-like and MHC-II antigen presenting subtype SCs are associated with increased myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors revealed Injury-like tumors are associated with larger tumor size, and scATAC-seq identified transcription factors associated with nerve repair among SCs from Injury-like tumors. Ligand-receptor analysis and functional in vitro experiments suggested that SCs recruit monocytes. Our study indicates that Injury-like SCs may cause tumor growth via myeloid cell recruitment and identifies molecular pathways that may be targeted to prevent tumor progression.

cancer biology↗

bioRxiv2021

The conventional dendritic cell 1 subset primes CD8+ T cells and traffics tumor antigen to drive anti-tumor immunity in the brain

The central nervous system (CNS) antigen presenting cell (APC) which primes anti-tumor CD8+ T cell responses remains undefined. Elsewhere, the conventional dendritic cell 1 (cDC1) performs this role. However, steady-state brain cDC1 are rare; cDC localize to choroid plexus and dura. Using preclinical glioblastoma models and cDC1-deficient mice, we explored the role of cDC1 in CNS anti-tumor immunity. We determined that cDC1 mediate checkpoint blockade-induced survival benefit and prime neoantigen-specific CD8+ T cells against brain tumors. We observed that cDC, including cDC1, isolated from the tumor, the dura, and the CNS-draining cervical lymph nodes harbored a traceable fluorescent tumor-antigen. In patient samples, we observed several APC subsets (including the CD141+ cDC1-equivalent) infiltrating glioblastomas, meningiomas, and dura. In these same subsets, we identified a tumor-specific fluorescent metabolite of 5- aminolevulinic acid, which labels tumor cells during fluorescence-guided glioblastoma resection. Together, these data elucidate the specialized behavior of cDC1 and suggest cDC1 play a significant role in CNS anti-tumor immunity. One Sentence SummaryCNS cDC1 engage in previously undefined behavior to establish immune responses against brain tumors.

immunology↗