A5110967582- Neurofibromatosis and Schwannoma Cases
- Vascular Malformations and Hemangiomas
- Glioma Diagnosis and Treatment
- Sarcoma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Cardiac tumors and thrombi
- Single-cell and spatial transcriptomics
- Gastrointestinal Tumor Research and Treatment
- MicroRNA in disease regulation
- Congenital heart defects research
- Neurogenesis and neuroplasticity mechanisms
- Cancer Research and Treatments
- Protein Tyrosine Phosphatases
- Cancer Cells and Metastasis
- Cancer, Hypoxia, and Metabolism
- RNA and protein synthesis mechanisms
- TGF-β signaling in diseases
- RNA Research and Splicing
- Chromatin Remodeling and Cancer
- Hedgehog Signaling Pathway Studies
- Cancer Genomics and Diagnostics
- Myasthenia Gravis and Thymoma
- Bone Tumor Diagnosis and Treatments
- Protein Kinase Regulation and GTPase Signaling
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
Memorial Sloan Kettering Cancer Center
2016-2024
Kettering University
2018-2024
Medical College of Wisconsin
2022-2024
College Station Medical Center
2024
Children’s Institute
2024
Cancer Genetics (United States)
2020
Wayne State University
2010-2015
The University of Texas Southwestern Medical Center
2015
The Barbara Ann Karmanos Cancer Institute
2010-2013
Beijing Radiation Center
2006
Significance Adult neural stem cells (NSC) are closely related to multiple neurological disorders and brain tumors. Comprehensive investigation of their composition, lineage, aging will provide insights that may lead enhanced patient treatment. This study applies a transgene label manipulate stem/progenitor monitor evolution during aging. Together with high-throughput single-cell RNA sequencing, we able analyze the subventricular zone from infancy advanced age unprecedented granularity....
Abstract Background Wnt/β-catenin pathway has critical roles in development and oncogenesis. Although significant progress been made understanding the downstream signaling cascade of this pathway, little is known regarding modification cellular apoptosis. Methods To identify potential genes regulated by involved apoptosis, we used a stably integrated, inducible RNA interference (RNAi) vector to specific inhibit expression transcriptional activity β-catenin HeLa cells. Meanwhile, designed an...
Macrophage targeting therapies have had limited clinical success in glioblastoma (GBM). Further understanding the GBM immune microenvironment is critical for refining immunotherapeutic approaches. Here, we use genetically engineered mouse models and orthotopic transplantation-based with identical driver mutations unique cells of origin to examine role tumor cell lineage shaping response tumor-associated macrophage (TAM) depletion therapy. We show that oligodendrocyte progenitor...
Malignant peripheral nerve sheath tumors (MPNST) are a type of soft tissue sarcoma that can be associated with germline mutations in Neurofibromatosis 1 (NF1) or may occur sporadically.Although the etiology MPNST is poorly understood, it clear loss function NF1 gene, encoding Ras-GAP, an important factor tumorigenesis inherited form MPNST.Tumor latency patients suggests additional mutational events probably required for malignancy.In order to define oncogene 5 cell lines, we assayed 238 most...
Malignant peripheral nerve sheath tumor (MPNST) is a type of soft tissue sarcoma that occurs in carriers germline mutations Nf1 gene as well sporadically. Neurofibromin, encoded by the gene, functions GTPase-activating protein (GAP) whose mutation leads to activation wt-RAS and mitogen-activated kinase (MAPK) signaling neurofibromatosis I (NF1) patients' tumors. However, therapeutic targeting RAS MAPK have had limited success this disease. In study, we modulated NRAS, protein/extracellular...
Abstract Background Local structures of target mRNAs play a significant role in determining the efficacies antisense oligonucleotides (ODNs), but some structure-based site selection methods are limited by uncertainties RNA secondary structure prediction. If all predicted given mRNA within certain energy limit could be used simultaneously, would obviously improved both reliability and efficiency. In this study, key problems ODN on basis multiple systematically discussed. Results Two were...
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). These malignancies develop within preexisting benign lesions called plexiform neurofibromas (PNs). PNs solely driven by biallelic NF1 loss eliciting RAS pathway activation, they respond favorably to MEK inhibitor therapy. MPNSTs harbor additional mutations poorly inhibition. Our analysis genetically engineered orthotopic patient-derived...
Abstract Germline pathogenic variants in the RAS/mitogen‐activated protein kinase (MAPK) signaling pathway are molecular cause of RASopathies, a group clinically overlapping genetic syndromes. RASopathies constitute wide clinical spectrum characterized by distinct facial features, short stature, predisposition to cancer, and variable anomalies nearly all major body systems. With increasing global recognition these conditions, 8th International Symposium spotlighted perspectives on care...
Abstract Malignant peripheral nerve sheath tumor is a type of soft-tissue sarcoma that arises from the neural crest lineage and commonly associated with trunks. Surgical removal major treatment conjugated chemo/radiation therapy when applicable. However, complete clearance limited by resectability, especially large such as sciatic nerve, brachial plexus, sacral plexus. The local recurrence MPNST 40-45% distal 40-48%. By harnessing our Nes-hsvTK-GFP transgene successfully labeled cancer stem...
Neurofibromatosis Type 1 (NF1) is one of the most common genetic tumor predisposition syndromes, affecting up to in 2500 individuals. Up half patients with NF1 develop benign nerve sheath tumors called plexiform neurofibromas (PNs), characterized by biallelic loss. PNs can grow immense sizes, cause extensive morbidity, and harbor a 15% lifetime risk malignant transformation. Increasingly, molecular sequencing drug screening data from various preclinical murine human PN cell lines, models,...
Abstract Neurofibromatosis type I (NF1)-deficient malignant peripheral nerve sheath tumor (MPNST) is an aggressive for which the only treatment option surgical removal with wide margins, often leaving behind cancer cells needing chemotherapy. Ras-GAP related domain (GRD) most widely studied functional target of Nf1 implicated in tumorigenesis, however, therapeutic interventions targeting Ras activity have met limited success. Using gene expression profiling, we identified bone morphogenetic...
Abstract Our lab has identified and validated bone morphogenetic protein 2 (BMP2) signaling pathways as a therapeutic target in malignant peripheral nerve sheath tumors (MPNSTs), independent of the NRAS MEK1/2 regulation. BMP2/SMAD is associated with enhanced motility invasion, hallmark feature biological aggressiveness MPNSTs. We have shown that inhibition BMP2 leads to decreased invasiveness MPNST cell lines. Consistent our data, gene expression studies from NF1 patient tissue samples...
Abstract A central question in glioblastoma multiforme (GBM) research is the hierarchy of tumor-initiating cells, and its contribution to malignant phenotype genomic make-up GBM. We examine potential adult lineage restricted nervous system (CNS) progenitors form gliomas. show that targeting Nf1,p53 Pten mutations CNS but not stem cells gives rise fully penetrant identify two phenotypically molecularly distinct GBM subtypes arise from different progenitor lineages. Using multiple inducible...