A5028367199- Sarcoma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Neuroblastoma Research and Treatments
- Cancer Cells and Metastasis
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- CAR-T cell therapy research
- Protein Degradation and Inhibitors
- Virus-based gene therapy research
- Ovarian cancer diagnosis and treatment
- Cancer Research and Treatments
- Orthopedic Infections and Treatments
- Cancer Diagnosis and Treatment
- Pleural and Pulmonary Diseases
- Cytokine Signaling Pathways and Interactions
- Immune cells in cancer
- Ubiquitin and proteasome pathways
- Single-cell and spatial transcriptomics
- Lymphoma Diagnosis and Treatment
- Radiopharmaceutical Chemistry and Applications
- Molecular Biology Techniques and Applications
- Musculoskeletal synovial abnormalities and treatments
- Soft tissue tumors and treatment
Nationwide Children's Hospital
2016-2025
The Ohio State University
2012-2024
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2018-2024
The Ohio State University Wexner Medical Center
2020-2024
Cincinnati Children's Hospital Medical Center
2022-2023
University of Cincinnati Medical Center
2022-2023
Roswell Park Comprehensive Cancer Center
2021
GlaxoSmithKline (United Kingdom)
2019
Harvard University
2018
University of Missouri–Kansas City
2007
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
Abstract Tumor-educated macrophages facilitate tumor metastasis and angiogenesis. We discovered that granulocyte macrophage colony-stimulating factor (GM-CSF) blocked vascular endothelial growth (VEGF) activity by producing soluble VEGF receptor-1 (sVEGFR-1) determined the effect on tumor-associated behavior growth. show GM-CSF treatment of murine mammary tumors slowed metastasis. These had more macrophages, fewer blood vessels, lower oxygen concentrations. This was sVEGFR-1 dependent. In...
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...
Abstract Rhabdomyosarcoma (RMS) is an aggressive pediatric tumor with a poor prognosis for metastasis and recurrent disease. Large-scale sequencing endeavors demonstrate that Rhabdomyosarcomas have dearth of precisely targetable driver mutations. However, IGF-2 signaling known to be grossly altered in RMS. The insulin receptor (IR) exists two alternatively spliced isoforms, IR-A IR-B. molecule binds both its innate IGF-1 as well the variant A ( ) high affinity. Mitogenic proliferative via...
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...
Pharmacologic therapies for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PNs) are limited; currently, none US Food and Drug Administration-approved adults.
M-CSF recruits mononuclear phagocytes which regulate processes such as angiogenesis and metastases in tumors. VEGF is a potent activator of it promotes endothelial cell proliferation new blood vessel formation. Previously, we reported that vitro induces the expression biologically-active from human monocytes.In this study, demonstrate molecular mechanism M-CSF-induced production. Using construct containing promoter linked to luciferase reporter, found mutation reducing HIF binding had no...
Successful treatment of neurofibromatosis type 1 (NF1)-associated tumors poses a significant clinical challenge. While the primary underlying genetic defect driving RAS signaling is well described, recent evidence suggests immune dysfunction contributes to tumor pathogenesis and malignant transformation. As immunologic characterizations, prognostic predictive immunotherapeutic response in other cancers, are not fully described for benign NF1-related tumors, we sought define their profiles....
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....
Lessons from extinction can be used in trials designed to pursue a cure for cancer. When cancer cannot cured, similar strategies may unwise, and that leverage the adaptations of therapy should considered.
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...
11508 Background: Trabectedin(T) is a marine-derived minor groove DNA binding compound that alters transcription factor activity. Preclinical data suggests T suppresses the oncogenic driver of ES, EWS::FLI1. This suppression requires threshold concentration and potentiated by low doses Irinotecan(I). Preliminary clinical activity reversal EWS::FLI1 transcriptome was seen in patients (pts) phase I portion SARC037. Here we report II results with at recommended dose pts relapsed/refractory ES....
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>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...