A5049545563- Cancer Genomics and Diagnostics
- Sarcoma Diagnosis and Treatment
- Cancer Cells and Metastasis
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Cancer, Stress, Anesthesia, and Immune Response
- Tryptophan and brain disorders
- Pharmacological Receptor Mechanisms and Effects
- RNA Research and Splicing
- Cancer Diagnosis and Treatment
- Orthopedic Infections and Treatments
- Cancer Research and Treatments
- Pleural and Pulmonary Diseases
- Immune cells in cancer
- Virus-based gene therapy research
- Single-cell and spatial transcriptomics
- Cytokine Signaling Pathways and Interactions
- CAR-T cell therapy research
- Musculoskeletal synovial abnormalities and treatments
- Soft tissue tumors and treatment
- Cancer, Hypoxia, and Metabolism
- Molecular Biology Techniques and Applications
- Nanoplatforms for cancer theranostics
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
Nationwide Children's Hospital
2016-2025
The Ohio State University
2008-2023
Lung Institute
2020
West Virginia University
2016
The Ohio State University Wexner Medical Center
2011-2014
Institute for Behavioral Medicine
2008-2011
Recent studies have shown the importance of dynamic tumor microenvironment (TME) in high-grade gliomas (HGGs). In particular, myeloid cells are known to mediate immunosuppression glioma; however, it is still unclear if play a role low-grade glioma (LGG) malignant progression. Here, we investigate cellular heterogeneity TME using single-cell RNA sequencing murine model that recapitulates progression LGG HGG. LGGs show increased infiltrating CD4
Reports demonstrate the role of M-CSF (CSF1) in tumor progression mouse models as well prognostic value macrophage numbers breast cancer patients. Recently, a subset CD14+ monocytes expressing Tie2 receptor, once thought to be predominantly expressed on endothelial cells, has been characterized. We hypothesized that increased levels CSF1 tumors can regulate differentiation Tie2- Tie2+ phenotype. treated human with and found significant increase CD14+/Tie2+ positivity. To understand if...
Osteosarcoma (OS), a malignant tumor of bone, kills through aggressive metastatic spread almost exclusively to the lung. Mechanisms driving this tropism for lung tissue remain unknown, though likely invoke specific interactions between cells and other within niche. Aberrant overexpression ΔNp63 in OS directly drives production IL-6 CXCL8. All these factors were expressed at higher levels metastases than matched primary tumors from same patients. Expression cell lines correlated strongly with...
Aggressive metastatic breast cancer cells seemingly evade surgical resection and current therapies, leading to colonization in distant organs tissues poor patient prognosis. Therefore, high-throughput vitro tools allowing rapid, accurate, novel anti-metastatic drug screening are grossly overdue. Conversely, aligned nanofiber constitutes a prominent component of the late-stage tumor margin extracellular matrix. This parallel suggests that use synthetic ECM form nanoscale model could provide...
Abstract Background Tumors are complex tissues containing collections of phenotypically diverse malignant and nonmalignant cells. We know little the mechanisms that govern heterogeneity tumor cells nor role plays in overcoming stresses, such as adaptation to different microenvironments. Osteosarcoma is an ideal model for studying these mechanisms—it exhibits widespread inter- intra-tumoral heterogeneity, predictable patterns metastasis, a lack clear targetable driver mutations. Understanding...
<p>scRNA-seq marker expression and protein level validation of macrophage epithelial cell enrichment</p>
<p>Niche-wide changes in target signaling pathway activity with immediate and delayed nintedanib</p>
<p>Immediate vs delayed treatment, tumor burden-based randomization</p>
<div>AbstractPurpose:<p>Lung metastasis is responsible for nearly all deaths caused by osteosarcoma, the most common pediatric bone tumor. How malignant cells coerce lung microenvironment to support metastatic growth unclear. The purpose of this study identify metastasis-specific therapeutic vulnerabilities delineating cellular and molecular mechanisms underlying osteosarcoma niche formation.</p>Experimental Design:<p>Using single-cell RNA sequencing, we characterized...
<p>Chronic wound epithelial cells (KRT8+) accumulate in human patient osteosarcoma lung metastasis</p>
<p>Unaffected thick tissue epithelial z-stack</p>
<p>Metastasis thick tissue epithelial z-stack</p>
<p>Tumor cell-intrinsic effects of nintedanib</p>
<p>K7M2 shows evidence of acute alveolar injury during osteosarcoma metastasis</p>
<p>Mechanistic and pharmacodynamic effects of nintedanib</p>
<p>Ligand-Receptor-Target (NicheNET) gene expression analysis</p>
Ewing sarcoma (EWS) is the second most common and aggressive type of metastatic bone tumor in adolescents young adults. There unmet medical need to develop test novel pharmacological targets therapies treat EWS. Here, we found that EWS expresses high levels a p53 isoform, delta133p53. We further determined aberrant expression delta133p53 induced HGF secretion resulting growth metastasis. Thereafter, evaluated targeting tumors with receptor neutralizing antibody (AMG102) preclinical studies....
Osteosarcoma is an aggressive malignancy characterized by high genomic complexity. Identification of few recurrent mutations in protein coding genes suggests that somatic copy-number aberrations (SCNA) are the genetic drivers disease. Models around instability conflict-it unclear whether osteosarcomas result from pervasive ongoing clonal evolution with continuous optimization fitness landscape or early catastrophic event followed stable maintenance abnormal genome. We address this question...
Lung metastasis is responsible for nearly all deaths caused by osteosarcoma, the most common pediatric bone tumor. How malignant cells coerce lung microenvironment to support metastatic growth unclear. The purpose of this study identify metastasis-specific therapeutic vulnerabilities delineating cellular and molecular mechanisms underlying osteosarcoma niche formation.
Abstract Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma and associated with arrested skeletal muscle differentiation. RMS poses considerable challenges in both diagnosis treatment, presence of fusion oncogenes predictive more aggressive forms disease. There a lack mechanistic understanding fusion-oncogene-driven tumorigenesis. Thus, efforts need to be directed toward defining fusion-oncogene biology identify novel therapeutic strategies improve clinical outcomes...
Multiple studies have indicated that in addition to direct oncolysis, virotherapy promotes an antitumor cytotoxic T cell response important for efficacy. To study this phenomenon further, we tested three syngeneic murine sarcoma models displayed varied degrees of permissiveness oncolytic herpes simplex virus replication and cytotoxicity vitro, with the most permissive being comparable some human tumor lines. The vivo effect ranged from no or modest complete regression protection rechallenge....
The four variables, hypoxia, acidity, high glutathione (GSH) concentration and fast reducing rate (redox) are distinct varied characteristics of solid tumors compared to normal tissue. These parameters among the most significant factors underlying metabolism physiology tumors, regardless their type or origin. Low oxygen tension contributes both inhibition cancer cell proliferation therapeutic resistance tumors; low extracellular pH, reverse cells, mainly enhances tumor invasion; dysregulated...
Abstract Desmoplastic small round cell tumor (DSRCT) is a rare pediatric sarcoma with poor overall survival. This absolutely dependent on the continued expression and activity of its defining molecular lesion, EWS–WT1 transcription factor. Unfortunately, therapeutic targeting factors challenging, there critical need to identify compounds that inhibit EWS–WT1. Here we show compound lurbinectedin inhibits by redistributing protein within nucleus nucleolus. nucleolar redistribution interferes...
Oncolytic viruses, modified for tumor-restricted infection, are a promising cancer immunotherapeutic, yet much remains to be understood about factors driving their activity and outcome in the tumor microenvironment. Here, we report that oncolytic herpes simplex virus C134, previously found exert T cell-dependent efficacy mouse models of glioblastoma, exerts cell-independent medulloblastoma, indicating this uses different mechanisms tumors. We investigated C134's behavior medulloblastomas,...