Jennifer Hadley
A5012320016- Glioma Diagnosis and Treatment
- Single-cell and spatial transcriptomics
- Cancer-related molecular mechanisms research
- Protein Degradation and Inhibitors
- Radiomics and Machine Learning in Medical Imaging
- Hedgehog Signaling Pathway Studies
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Ocular Oncology and Treatments
- Histone Deacetylase Inhibitors Research
- Cardiac Arrhythmias and Treatments
- MRI in cancer diagnosis
- Genomics and Chromatin Dynamics
- Mathematical Biology Tumor Growth
- RNA Research and Splicing
- Microtubule and mitosis dynamics
- Advanced Radiotherapy Techniques
- Kruppel-like factors research
- Developmental Biology and Gene Regulation
- Chromatin Remodeling and Cancer
- Advanced Computing and Algorithms
- Meningioma and schwannoma management
- CNS Lymphoma Diagnosis and Treatment
- Mitochondrial Function and Pathology
- Dental Research and COVID-19
St. Jude Children's Research Hospital
2018-2025
University of Washington
2009
Washington University in St. Louis
2007-2008
Brown Foundation
2007
St. Luke's Episcopal Hospital
2007
The University of Texas Health Science Center at Houston
2007
University of Cincinnati Medical Center
2007
The cerebellum develops from a restricted number of cell types that precisely organize to form the circuitry controls sensory-motor coordination and some higher-order cognitive processes. To acquire an enhanced understanding molecular processes mediate cerebellar development, we performed single-cell RNA-sequencing 39,245 murine cells at twelve critical developmental time points. Using recognized lineage markers, confirmed data accurately recapitulate development. We then followed distinct...
Children with average-risk medulloblastoma (MB) experience survival rates of ≥ 80% at the expense adverse consequences treatment. Efforts to mitigate these effects include deintensification craniospinal irradiation (CSI) dose and volume.ACNS0331 (ClinicalTrials.gov identifier: NCT00085735) randomly assigned patients age 3-21 years MB receive posterior fossa radiation therapy (PFRT) or involved field (IFRT) following CSI. Young children (3-7 years) were also standard-dose CSI (SDCSI; 23.4 Gy)...
Glioblastoma multiforme (GBM) are aggressive and uniformly fatal primary brain tumors characterized by their diffuse invasion of the normal-appearing parenchyma peripheral to clinical imaging abnormality. Hypoxia, a hallmark tumor behavior often noted in GBMs, has been associated with resistance therapy, poorer survival, more malignant phenotypes. Based on existence set novel techniques modeling tools, our objective was assess hypothesized quantitative link between growth kinetics [assessed...
<h3>Importance</h3> Brain tumors are the leading cause of disease-related death in children. Medulloblastoma is most common malignant embryonal brain tumor, and strategies to increase survival needed. <h3>Objective</h3> To evaluate therapy intensification with carboplatin as a radiosensitizer isotretinoin proapoptotic agent children high-risk medulloblastoma randomized clinical trial and, correlative biology study, facilitate planned subgroup analysis according World Health Organization...
Abstract Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% G4 medulloblastoma). In contrast, highly similar SHH distinct diametrically opposed gain-of-function mutations copy number gains (20% Overexpression...
Abstract Background Distinguishing the cellular origins of childhood brain tumors is key for understanding tumor initiation and identifying lineage-restricted, tumor-specific therapeutic targets. Previous strategies to map cell-of-origin typically involved comparing human murine embryonal tissues, which potentially limited due species-specific differences. The aim this study was unravel 3 most common pediatric tumors, ependymoma, pilocytic astrocytoma, medulloblastoma, using a developing...
Human hypertrophic cardiomyopathy, characterized by cardiac hypertrophy and myocyte disarray, is the most common cause of sudden death in young. Hypertrophic cardiomyopathy often caused mutations sarcomeric genes. We sought to determine arrhythmia propensity underlying mechanisms contributing a transgenic (TG) rabbit model (beta-myosin heavy chain-Q403) human cardiomyopathy. Langendorff-perfused hearts from TG (n=6) wild-type (WT) rabbits were optically mapped. The upper lower limits...
Cancer mutations can create neomorphic protein-protein interactions to drive aberrant function 1 . As a substrate receptor of the CULLIN3-RBX1 E3 ubiquitin ligase complex, KBTBD4 is recurrently mutated in medulloblastoma (MB) 2 , most common embryonal brain tumor children, and pineoblastoma 3 These impart gain-of-function induce degradation transcriptional corepressor CoREST 4 However, their mechanism action remains unresolved. Here, we elucidate mechanistic basis by which promote through...
Embryonal tumors of the CNS are most common malignant occurring in first years life. This study evaluated feasibility and safety incorporating novel non-cytotoxic therapy with vorinostat isotretinoin to an intensive cytotoxic chemotherapy backbone.PBTC-026 was a prospective multi-institutional clinical trial for children <48 months age newly diagnosed embryonal CNS. Treatment included three 21-day cycles induction isotretinoin, cisplatin, vincristine, cyclophosphamide, etoposide; 28-day...
Understanding the cellular origins of childhood brain tumors is key for discovering novel tumor-specific therapeutic targets. Previous strategies mapping typically involved comparing human to murine embryonal tissues 1,2 , a potentially imperfect approach due spatio-temporal gene expression differences between species 3 . Here we use an unprecedented single-nucleus atlas developing cerebellum (Sepp, Leiss, et al) and extensive bulk single-cell transcriptome tumor data map their with focus on...
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 &gt;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 &gt;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...
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 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 Medulloblastoma (MB) is a highly malignant childhood cerebellar tumor comprising collection of molecularly and clinically distinct entities. Group 3 4-MB subgroups originate from overlapping progenitor pools the developing rhombic lip when neuronal differentiation hierarchies are subverted through somatic alterations. Mutations suspected to deregulate activity chromatin-modifying genes pervasive in 4-MB. However, molecular consequences these alterations remain largely...
Abstract Germline loss-of-function (LOF) mutations in Elongator complex protein 1 (ELP1) are found 15-20% of childhood SHH medulloblastoma (MB) and exceedingly rare non-SHH-MB or other cancers. ELP1 germline carriers that develop SHH-MB harbor frequent somatic PTCH1 universally sustain loss-of-heterozygosity the remaining allele through chromosome 9q deletion. functions as a scaffolding subunit is required for posttranscriptional modification tRNAs maintenance efficient translational...
Abstract Identification and characterization of lineage-specific beginnings distinct medulloblastoma (MB) subgroups is a fundamental challenge in the field. Genetically engineered mouse models cross-species transcriptomics have provided mounting evidence discrete, subgroup-specific developmental origins. Likewise, murine single-cell transcriptional atlases cerebellar development recently further clues into MB subgroup origins, particularly for poorly defined Group 3 4-MB. However, initial...
<div>Abstract<p>Glioblastoma multiforme (GBM) are aggressive and uniformly fatal primary brain tumors characterized by their diffuse invasion of the normal-appearing parenchyma peripheral to clinical imaging abnormality. Hypoxia, a hallmark tumor behavior often noted in GBMs, has been associated with resistance therapy, poorer survival, more malignant phenotypes. Based on existence set novel techniques modeling tools, our objective was assess hypothesized quantitative link...
Free Article from Quantitative Metrics of Net Proliferation and Invasion Link Biological Aggressiveness Assessed by MRI with Hypoxia FMISO-PET in Newly Diagnosed Glioblastomas