A5051203146- Glioma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Virus-based gene therapy research
- RNA Research and Splicing
- Chromatin Remodeling and Cancer
- RNA modifications and cancer
- interferon and immune responses
- Sirtuins and Resveratrol in Medicine
- Cancer-related molecular mechanisms research
- RNA Interference and Gene Delivery
- Protein Degradation and Inhibitors
- Cholesterol and Lipid Metabolism
- Cancer, Lipids, and Metabolism
- Epigenetics and DNA Methylation
- IL-33, ST2, and ILC Pathways
- Renal and related cancers
- Acute Lymphoblastic Leukemia research
- Advanced Proteomics Techniques and Applications
- Pluripotent Stem Cells Research
- Single-cell and spatial transcriptomics
- Caveolin-1 and cellular processes
- Galectins and Cancer Biology
- Cancer, Hypoxia, and Metabolism
- MicroRNA in disease regulation
- ATP Synthase and ATPases Research
University of Georgia
2023-2025
Memorial Sloan Kettering Cancer Center
2014-2024
Kettering University
2021-2024
The University of Tokyo
2011-2018
Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail histone H3.3. The role H3.3K27M mutation tumorigenesis is not fully understood. Here, we use human embryonic stem cell system to model this tumor. We show expression synergizes with p53 loss and PDGFRA activation neural progenitor cells derived from cells, resulting neoplastic transformation....
Significance Diffuse intrinsic pontine glioma (DIPG) is an incurable childhood cancer with a median survival of less than 1 y. Characterization druggable targets in this disease remains longstanding goal, as no pharmacological agents have proven efficacy malignancy. We recently identified the menin inhibitor, MI-2, exhibiting potent antitumor activity preclinical models DIPG. Here, we show that MI-2 exerts its largely independent ability to target epigenetic regulator menin, but instead by...
Radial glia (RG) cells are the first neural stem to appear during embryonic development. Adult human glioblastomas harbor a subpopulation of RG-like with typical RG morphology and markers. The exhibit classic unique mitotic behavior normal in cell-autonomous manner. Single-cell RNA sequencing analyses glioblastoma reveal transcriptionally dynamic clusters that share profiles fetal radial reside quiescent cycling states. Functional assays show role for interleukin triggering exit from...
PTPRD is a receptor-type tyrosine-protein phosphatase. Recent analyses of comprehensive mutations and copy numbers have revealed that frequently mutated homozygously deleted in various types cancer, including glioblastoma, melanoma, breast colon cancer. However, the molecular functions cancer progression yet to be elucidated. Herein, suppressed cell migration was required for appropriate cell-cell adhesion. In addition, regulated cooperation with β-catenin/TCF signaling its target CD44....
Allergic airway inflammation is one of the primary features allergic asthma. Interleukin-33 (IL-33) recognized as a key pro-inflammatory cytokine that mediates inflammation, and its expression elevated in this condition, but little known about regulatory mechanisms underlying IL-33 induction. Here, we show RNA binding protein Mex-3B plays critical role induction development inflammation. We generated Mex3b(-/-) mice found they develop significantly less than wild-type due to reduced IL-33....
Glycosaminoglycans (GAGs) are linear, heterogeneous polysaccharides expressed on all animal cells. Sulfated GAGs, including heparan sulfate (HS) and chondroitin/dermatan (CS/DS), involved in numerous physiological pathological processes; therefore, precise robust analytical methods for their characterization essential to correlate structure function. In this study, we developed a method utilizing hydrophilic interaction liquid chromatography coupled with time-of-flight mass spectrometry...
Recurrent driver mutations in the genes encoding histones have been recently described pediatric brain tumors, as well chondroblastomas and giant cell tumors of bone. The are often heterozygous frequently comprise single amino acid substitutions tails histone variants. Substitutions methionine to lysine on H3.3K27 or H3.3K36 most common alterations, occurring diffuse intrinsic pontine gliomas (DIPGs) chondroblastomas, respectively. Current data suggest that alter epigenetic landscape tumor...
Glioblastoma multiforme (GBM) is the most common and aggressive primary intracranial brain tumor in adults with a mean survival of 14 to 15 months. Aberrant activation epidermal growth factor receptor (EGFR) plays significant role GBM progression, amplification or overexpression EGFR 60% tumors. To target expressed by GBM, we have developed strategy deliver coding sequence for cetuximab, an anti-EGFR antibody, directly CNS using adeno-associated virus serotype rh.10 gene transfer vector. The...
NOVA1 is a neuronal RNA-binding protein identified as the target antigen of rare autoimmune disorder associated with cancer and neurological symptoms, termed paraneoplastic opsoclonus-myoclonus ataxia. Despite strong association between cancer, it has been unclear how function might contribute to biology. In this study, we find that acts an oncogenic factor in GBM (glioblastoma multiforme) cell line established from patient. Interestingly, Argonaute (AGO) CLIP common 3′ untranslated region...
Abstract Background FOXR2-activated central nervous system (CNS) neuroblastoma (CNS NB-FOXR2) is a recently identified subtype of brain tumor characterized by the elevated expression transcription factor FOXR2 mainly due to genomic rearrangements. However, precise pathogenic mechanisms, including cell type origin, remain elusive. Methods A gene analysis patient tumors was performed identify putative types origin. Based on this prediction, new human embryonic stem cell–based model developed...
Abstract FOXR2-activated CNS neuroblastoma is a rare subtype of pediatric brain tumor characterized by the elevated expression transcription factor FOXR2 due to genomic rearrangement. However, precise pathogenic mechanisms, including cell type origin and function FOXR2, are not fully understood. An profile analysis patient tumors showed increased marker genes associated with Medial Ganglionic Eminence (MGE) in ventral forebrain such as NKX2.1 SOX6. Based on this result, we hypothesized that...
Growing evidence indicates that childhood cancer is a developmental disease and the oncogenic impact of mutations depends on spatiotemporal contexts. This dependency leads to distinct molecular, genetic, clinical characteristics across various (sub)types. However, underlying molecular mechanisms tumorigenesis are not fully understood, development precision medicine for cancers still an ongoing effort, partially due their relative rarity. Therefore, it crucial develop use "developmental...
Abstract Despite huge efforts, glioblastoma has remained one of the most intractable tumors. According to cancer stem cell theory, aggressive phenotype and poor prognosis are attributed rare tumor cells called (GSCs), which poorly differentiated share features with neural cells. However, molecular mechanisms underlying tumorigenicity stemness GSCs still be elucidated. In this study, we performed an RNA-interference (RNAi)-based screen identified 29 genes that positively regulate expression...
Recent sequencing data demonstrate the presence of novel mutations in H3.3. histone gene variant diffuse intrinsic brainstem gliomas childhood, DIPG. Surgical access to these tumors presents high risks, leading a paucity patient specimens and poor understanding this tumor's biology. We used human embryonic stem cells differentiated into early neural precursors as system model H3.3K27M tumors. vitro vivo neoplastic transformation cells, following expression gene, well combination PDGFRA p53....
Epidermal growth factor receptor (EGFR) is an attractive target for the treatment of glioblastoma (GBM), where deregulated expression or activity EGFR has been associated to tumor development, progression and spread, decreased survival. Systemic administration anti-EGFR antibody (CetuximabTM) reduces cellular proliferation in a variety cancer models, but GBM, efficacy limited by blood-brain barrier, only ~ 0.1% circulating antibodies reach brain. To circumvent these limitations, we have...
Abstract FOXR2-activated CNS neuroblastoma is a recently identified subtype of brain tumor characterized by genomic rearrangements at the FOXR2 locus and elevated expression transcription factor FOXR2. However, precise mechanisms underlying tumorigenesis this specific subtype, including cell type origin, are not fully understood. In study, we established new model using human embryonic stem cells (hESCs) to determine origin pathogenic mechanisms. Expression profile analysis patient tumors...
Diffuse intrinsic pontine glioma (DIPG) remains a uniformly fatal childhood tumor for which novel pharmacological treatments are desperately needed. In recent work, we performed small molecule screen in pre-clinical DIPG model, identifying MI-2 as the top ‘hit’, showing anti-tumor activity vitro and vivo. was developed an inhibitor of protein menin, epigenetic regulator has oncogenic acute leukemia. Here, characterize mechanism action DIPG. We generated menin knockout patient-derived...
H3.3G34R-mutant gliomas are lethal tumors of the cerebral hemispheres, with unknown mechanisms regional specificity and tumorigenicity. We developed a human embryonic stem cell-based model glioma that recapitulates key features tumors, anatomical to forebrain but not hindbrain cells. show H3.3G34R, ATRX TP53 mutations cooperatively impact alternative RNA splicing events, particularly suppression intron retention. This leads increased expression components Notch pathway, notably NOTCH2NL,...