A5057746696- Glioma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Hedgehog Signaling Pathway Studies
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- MicroRNA in disease regulation
- Neurofibromatosis and Schwannoma Cases
- Ocular Oncology and Treatments
- Protein Degradation and Inhibitors
- Neuroblastoma Research and Treatments
- Single-cell and spatial transcriptomics
- RNA regulation and disease
- Ferroptosis and cancer prognosis
- Cell Image Analysis Techniques
- Brain Metastases and Treatment
- DNA Repair Mechanisms
- Hippo pathway signaling and YAP/TAZ
- Sarcoma Diagnosis and Treatment
- RNA and protein synthesis mechanisms
- Meningioma and schwannoma management
- Genomics and Phylogenetic Studies
- Tumors and Oncological Cases
NKT Therapeutics (United States)
2025
St. Jude Children's Research Hospital
2019-2024
Washington University in St. Louis
2021
Clemson University
2015-2019
Abstract Long non-coding RNAs are involved in biological processes throughout the cell including nucleus, chromatin and cytosol. However, most lncRNAs remain unannotated functional annotation of is difficult due to their low conservation tissue developmentally specific expression. LncRNA subcellular localization highly informative regarding its function, although it discover because few prediction methods currently exist. While protein a well-established research field, lncRNA novel problem....
Pediatric high-grade glioma (pHGG) is a major contributor to cancer-related death in children. In vitro and vivo disease models reflecting the intimate connection between developmental context pathogenesis of pHGG are essential advance understanding identify therapeutic vulnerabilities. Here we report establishment 21 patient-derived orthotopic xenograft (PDOX) eight matched cell lines from diverse groups pHGG. These recapitulate histopathology, DNA methylation signatures, mutations gene...
Loss of heterozygosity (LOH) at 1p36 occurs in multiple cancers, including neuroblastoma (NBL). MYCN amplification and deletions tightly correlate with markers tumor aggressiveness NBL. Although distal losses associate single-copy tumors, larger amplification, indicating two suppressor regions 1p36, only one which facilitates oncogenesis. To better define this region, we genome-edited the syntenic locus primary mouse neural crest cells (NCCs), a putative NBL cell origin. In vitro...
Abstract The growing multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL) patient population which becomes refractory to available treatments requires new, effective convenient therapies with novel mechanisms of action. SKY-1214 is a small molecule that modulates splicing FANCL FANCI pre-mRNA, causing exon skipping introduction premature termination codons leading the downregulation mRNAs proteins. are critical components Fanconi anemia DNA damage repair pathway, contributes maintenance...
The advent of next-generation sequencing for genetic diagnoses complex developmental disorders, such as intellectual disability (ID), has facilitated the identification hundreds predisposing variants. However, there still exists a vast gap in our knowledge causal factors ID evidenced by low diagnostic yield screening, which identifiable causes are not found majority cases. Most methods screening focus on protein-coding genes; however, noncoding RNAs may outnumber genes and play important...
Medulloblastoma is a malignant childhood brain tumor arising from the developing cerebellum. In Sonic Hedgehog (SHH) subgroup medulloblastoma, aberrant activation of SHH signaling causes increased proliferation granule neuron progenitors (GNPs), and predisposes these cells to tumorigenesis. A second, cooperating genetic hit often required push hyperplastic malignancy confer mutation-specific characteristics associated with oncogenic signaling. Somatic loss-of-function mutations...
Genetic studies have identified many risk loci for autism spectrum disorder (ASD) although causal factors in the majority of cases are still unknown. Currently, known ASD genes all protein-coding genes; however, vast transcripts humans non-coding RNAs (ncRNAs) which do not encode proteins. Recently, long (lncRNAs) were shown to be highly expressed human brain and crucial normal development. We constructed a computational pipeline integration various genomic datasets identify lncRNAs...
Abstract During mammalian brain development, neural progenitor cells proliferate extensively but can ensure the production of correct numbers various types mature by balancing symmetric proliferative versus asymmetric differentiative cell divisions. This process fate determination may be harnessed for developing cancer therapy. Here, we test this idea targeting KIF20A, a mitotic kinesin crucial control division modes, in genetic model medulloblastoma (MB) and human MB cells. Inducible Kif20a...
Abstract SNCAIP duplication may promote Group 4 medulloblastoma via induction of PRDM6, a poorly characterized member the PRDF1 and RIZ1 homology domain-containing (PRDM) family transcription factors. Here, we investigated function PRDM6 in human hindbrain neuroepithelial stem cells tested as driver medulloblastoma. We report that localizes predominantly to nucleus, where it causes widespread repression chromatin accessibility complex alterations gene expression patterns. Genome-wide mapping...
Abstract Background Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas. Somatic inactivation of NF1 and cooperating tumor suppressors, including CDKN2A/B, PRC2, p53, is found in most MPNST. Inactivation LATS1/2 the Hippo pathway was recently shown to cause resembling MPNST histologically, although mutations rarely Because existing genetically engineered mouse (GEM) models do not recapitulate some key genetic features human MPNST, we aimed establish a GEM-MPNST model...
Abstract BACKGROUND Pineoblastoma (PB) is a rare and aggressive childhood brain tumor with highly variable outcomes. PB diagnostically characterized by expression of the photoreceptor identity transcription factor CRX, while tumors can be further classified into molecular subgroups (PB-miRNA1, PB-miRNA2, PB-MYC/FOXR2, PB-RB1), each marked unique clinico-molecular features. However, developmental origins subgroup heterogeneity mechanisms governing malignancy remain unknown. METHODS We...
Abstract A substantial fraction of Group 4 MBs are characterized by enhancer hijacking through tandem duplication SNCAIP, resulting in high expression PRDM6, a putative transcriptional repressor and histone methyltransferase. PRDM6 is poorly member the PRDF1 RIZ1 homology domain-containing (PRDM) family transcription factors. Here, we investigated function human hindbrain neuroepithelial stem cells its potential role as driver medulloblastoma. We report that localizes predominantly to...
Abstract Mouse models serve as invaluable tools for improving the understanding and treatment of pediatric brain tumors. We recently published a highly aggressive MYC-driven tumor model (GMYC), which exhibits approximately 70% penetrance. Our transcription profiling indicates that GMYC tumors accurately resemble human Group 3 medulloblastoma (MB-G3). Interestingly, strong photoreceptor program was activated in model. This is commonly upregulated MB-G3 but also pineoblastoma (PB), another...
Abstract BACKGROUND Medulloblastoma (MB), an aggressive pediatric brain cancer, poses significant treatment challenges due to its complex disease biology, comprising a collection of discrete molecular subtypes that require different treatment. Although the genomics, transcriptomics, and epigenetic landscapes biologically distinct MB subgroups are well-annotated have contributed enhanced diagnostics risk stratification, intersection these layers with proteome remains poorly defined METHODS To...
Abstract BACKGROUND Germline loss-of-function (LOF) variants in Elongator complex protein 1 (ELP1) are the most prevalent predisposing genetic events observed medulloblastoma (MB), accounting for 30% of Sonic Hedgehog 3 subtype (SHH-3). Molecularly, ELP1-associated SHH-MBs acquire somatic PTCH1 mutations >80% cases, and universal loss-of-heterozygosity wild-type ELP1 alleles through loss chromosome-arm 9q, resulting their biallelic inactivation. Notably, germline LOF occurs mutually...
Abstract Germline loss-of-function (LOF) variants in Elongator complex protein 1 (ELP1) are the most prevalent predisposing genetic events observed medulloblastoma (MB), accounting for 30% of Sonic Hedgehog 3 subtype (SHH-3). Molecularly, ELP1-associated SHH-MBs acquire somatic PTCH1 mutations >80% cases, and universal loss-of-heterozygosity wild-type ELP1 alleles through loss chromosome-arm 9q, resulting their biallelic inactivation. Notably, germline LOF occurs mutually exclusive...