A5089918335- Glioma Diagnosis and Treatment
- Mitochondrial Function and Pathology
- Anesthesia and Neurotoxicity Research
- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Cell death mechanisms and regulation
- Microtubule and mitosis dynamics
- Neuroblastoma Research and Treatments
- RNA Research and Splicing
- MicroRNA in disease regulation
- Cancer Research and Treatments
- Radiation Therapy and Dosimetry
- Genetic Syndromes and Imprinting
- Neuroinflammation and Neurodegeneration Mechanisms
- interferon and immune responses
- Advanced Breast Cancer Therapies
- Cancer-related Molecular Pathways
- Amino Acid Enzymes and Metabolism
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Cancer Mechanisms and Therapy
- Effects of Radiation Exposure
- Neurobiology and Insect Physiology Research
- Neurogenesis and neuroplasticity mechanisms
Emory University
2022-2025
University of Minnesota
2025
Mayo Clinic
2025
University of California, Los Angeles
2025
UNC Lineberger Comprehensive Cancer Center
2013-2023
University of North Carolina at Chapel Hill
2014-2023
Children's Center
2022-2023
Children's Healthcare of Atlanta
2023
Center for Neurosciences
2016-2023
University of North Carolina Hospitals
2023
We observed a syndrome of intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, livedoid rash, hepatosplenomegaly, systemic vasculopathy in three unrelated patients. suspected genetic cause because the disorder presented early childhood.We performed whole-exome sequencing initial patients their unaffected parents candidate-gene with similar phenotype, as well two young siblings polyarteritis nodosa one patient small-vessel vasculitis. Enzyme assays,...
OLIG2-expressing tumor stem cells have been shown to drive recurrence in Sonic Hedgehog (SHH)-subgroup medulloblastoma (MB) and patients urgently need specific therapies target this cell population. Here, we investigate the therapeutic potential of brain-penetrant orally bioavailable, OLIG2 inhibitor CT-179, using SHH-MB explant organoids, PDX GEM models. We find that CT-179 disrupts dimerization, phosphorylation DNA binding alters cell-cycle kinetics, increasing differentiation apoptosis....
Targeting oncogenic pathways holds promise for brain tumor treatment, but inhibition of Sonic Hedgehog (SHH) signaling has failed in SHH-driven medulloblastoma. Cellular diversity within tumors and reduced lineage commitment can undermine targeted therapy by increasing the probability treatment-resistant populations. Using single-cell RNA-seq tracing, we analyzed cellular medulloblastomas transgenic, medulloblastoma-prone mice, responses to SHH-pathway inhibitor vismodegib. In untreated...
The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and ability precisely manipulate genome. Despite importance genetics quality control (QC) not standardized, lack cost-effective, informative, robust platforms. Genotyping arrays are standard tools research remain an attractive alternative even era high-throughput whole-genome sequencing. Here, we describe content performance a new iteration...
Abstract Background Medulloblastoma (MB) is a heterogeneous disease in which neoplastic cells and associated immune contribute to progression. We aimed determine the influence of cell diversity on MB biology patient samples animal models. Methods To better characterize cellular heterogeneity we used single-cell RNA sequencing, immunohistochemistry, deconvolution transcriptomic data profile populations models across childhood subgroups. Results Neoplastic cluster primarily according...
While aerobic glycolysis is linked to unconstrained proliferation in cancer, less known about its physiological role. Why this metabolic program that promotes tumor growth preserved the genome has thus been unresolved. We tested hypothesis derives from developmental processes regulate rapid proliferation.
Abstract Background We previously reported promising pilot results treating patients with stage 4a metastatic retinoblastoma combined intensive conventional chemotherapy, high‐dose chemotherapy autologous hematopoietic stem cell rescue, and radiation therapy now present an expanded updated series. Procedure Fifteen bone marrow (n = 14), 10), orbit 9), and/or liver 4) disease were treated. Induction usually consisted of vincristine, cyclophosphamide, cisplatin, etoposide. The regimen included...
Alterations in genes that regulate brain size may contribute to both microcephaly and tumor formation. Here, we report Aspm, a gene is mutated familial microcephaly, regulates postnatal neurogenesis the cerebellum supports growth of medulloblastoma, most common malignant pediatric tumor. Cerebellar granule neuron progenitors (CGNPs) express Aspm when maintained proliferative state by Sonic Hedgehog (Shh) signaling, expressed Shh-driven medulloblastoma mice. Genetic deletion reduces...
The therapeutic potential of CDK4/6 inhibitors for brain tumors has been limited by recurrence. To address recurrence, we tested a nanoparticle formulation inhibitor palbociclib (POx-Palbo) in mice genetically-engineered to develop SHH-driven medulloblastoma, alone or combination with specific agents suggested our analysis. Nanoparticle encapsulation reduced toxicity, enabled parenteral administration, improved CNS pharmacokinetics, and extended mouse survival, but recurrence persisted....
Pharmacologic therapies for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PNs) are limited; currently, none US Food and Drug Administration-approved adults.
Microcephaly and medulloblastoma may both result from mutations that compromise genomic stability. We report ATR, which is mutated in the microcephalic disorder Seckel syndrome, sustains cerebellar growth by maintaining chromosomal integrity during postnatal neurogenesis. Atr deletion granule neuron progenitors (CGNPs) induced proliferation-associated DNA damage, p53 activation, apoptosis hypoplasia mice. Co-deletions of either or Bax Bak prevented Atr-deleted CGNPs, but failed to fully...
Aerobic glycolysis supports proliferation through unresolved mechanisms. We have previously shown that aerobic is required for the regulated of cerebellar granule neuron progenitors (CGNP) and growth CGNP-derived medulloblastoma. Blocking initiation via deletion hexokinase-2 (Hk2) disrupts CGNP restricts medulloblastoma growth. Here, we assessed whether disrupting pyruvate kinase-M (Pkm), an enzyme acts in terminal steps glycolysis, would alter metabolism, proliferation, tumorigenesis....
We report a nanoparticle formulation of the SHH-pathway inhibitor vismodegib that improves efficacy for medulloblastoma, while reducing toxicity. Limited blood–brain barrier (BBB) penetration and dose-limiting extitle/citraneural toxicities complicate systemic therapies brain tumors. Vismodegib is FDA-approved SHH-driven basal cell carcinoma, but implementation medulloblastoma has been limited by inadequate excessive bone To address these issues through optimized drug delivery, we formulated...
3016 Background: PN in patients (pts) with NF1 can cause pain, disfigurement, impaired quality of life (QoL), and undergo malignant transformation. ReNeu (NCT03962543), a multicenter, open-label, Phase 2b study, evaluated efficacy safety the highly selective, oral, investigational MEK1/2 inhibitor mirdametinib adult (≥18 y) pediatric (2-17 pts inoperable causing significant morbidities. Methods: Mirdametinib was administered as capsule or dispersible tablet (2 mg/m 2 BID, max 4 mg BID)...
Abstract Background The chromodomain, helicase DNA-binding protein 5 (CHD5) is a potential tumor suppressor gene located on chromosome 1p36, region recurrently deleted in high risk neuroblastoma (NB). Previous data have shown that CHD5 mRNA present normal neural tissues and low NB, nevertheless, the distribution of has not been explored. aim this study was to investigate expression as an immunohistochemical marker outcome NB. With purpose, analyzed neuroblastic tumors (NTs). reexamined after...
Maintenance of genomic integrity is critical during neurodevelopment, particularly in rapidly dividing cerebellar granule neuronal precursors that experience constitutive replication-associated DNA damage. As Dicer was recently recognized to have an unexpected function the damage response, we examined whether important for preserving developing brain. We report deletion mouse cerebellum resulted accumulation leading progenitor degeneration, which rescued with p53 deficiency; DGCR8 also...
Neuroectodermal tumor cells, like neural crest (NC) are pluripotent, proliferative, and migratory. We tested the hypothesis that genetic programs essential to NC development activated in neuroectodermal tumors. examined expression of transcription factors PAX3, PAX7, AP-2α, SOX10 human embryos tumors: neurofibroma, schwannoma, neuroblastoma, malignant nerve sheath tumor, melanoma, medulloblastoma, supratentorial primitive Ewing's sarcoma. also P0, ERBB3, STX, targets SOX10, respectively....
Cerebellar mutism syndrome (CMS) is a complication of posterior fossa surgery seen primarily in pediatric patients after resection medulloblastoma. CMS characterized by mutism, ataxia, hypotonia, and irritability. Currently, there no therapy proven efficacy. Zolpidem, although used as sedative, has been shown to alleviate promote arousal similar neurologic psychiatric disorders. Here, we describe child with severe whom zolpidem seemed increase arousal, accelerate the resolution decrease...
ABSTRACT Developing neurons extend long processes to specific distal targets using extracellular molecules as guidance cues navigate through the embryo. Growth cones, specialized structures at tip of extending processes, are thought accomplish this navigation receptors that recognize and modulate growth accordingly. In Drosophila, several receptor tyrosine phosphatases (rPTPs), including DLAR, have been shown participate in directing neurite outgrowth. As yet, however, it is not known how...
While treatments that induce DNA damage are commonly used as anticancer therapies, the mechanisms through which produces a therapeutic response incompletely understood. Here we have tested whether medulloblastomas must be competent for apoptosis to sensitive radiotherapy. Whether is required radiation sensitivity has been controversial. Medulloblastoma, most common malignant brain tumor in children, biologically heterogeneous set of tumors typically and chemotherapy; 80% medulloblastoma...