A5039646413- Glioma Diagnosis and Treatment
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Neuroblastoma Research and Treatments
- Extracellular vesicles in disease
- Cancer, Hypoxia, and Metabolism
- Cancer Genomics and Diagnostics
- Renal and related cancers
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurofibromatosis and Schwannoma Cases
- Brain Metastases and Treatment
- Chromatin Remodeling and Cancer
- Sarcoma Diagnosis and Treatment
- Inflammation biomarkers and pathways
- Cutaneous lymphoproliferative disorders research
- Neurological and metabolic disorders
- Mast cells and histamine
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Ferroptosis and cancer prognosis
- Vasculitis and related conditions
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Complement system in diseases
- Head and Neck Anomalies
- Moyamoya disease diagnosis and treatment
- Endometriosis Research and Treatment
University of Colorado Denver
2017-2025
University of Colorado Anschutz Medical Campus
2019-2024
University of Colorado Hospital
2021-2024
Children's Hospital Colorado
2021-2024
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...
Abstract Central nervous system (CNS) embryonal tumors are a heterogeneous group of high-grade malignancies, and the increasing clinical use methylation profiling next-generation sequencing has led to identification molecularly distinct subtypes. One proposed tumor type, CNS with BRD4::LEUTX fusion, been described. As only few fusions have described, we herein characterize cohort 9 such cases (4 new, 5 previously published) further describe their clinicopathologic molecular features. We...
Background Constitutively active PI3Kδ, as occurs in patients with activated PI3K-delta syndrome (APDS) 1, results disturbed immune cell development and function leading to microbial susceptibility dysregulation. Leniolisib, a novel, orally FDA-approved bioavailable small molecule inhibitor, was engineered selectively target PI3Kδ signaling. Leniolisib shown partially reconstitute lymphocyte subsets decrease lymphoproliferation measured by reduced spleen size lymphadenopathy. However, its...
Abstract Background Ependymoma (EPN) posterior fossa group A (PFA) has the highest rate of recurrence and worst prognosis all EPN molecular groups. At relapse, it is typically incurable even with re-resection re-irradiation. The biology recurrent PFA remains largely unknown; however, increasing use surgery at first now provided access to clinical samples facilitate a better understanding this. Methods In this large longitudinal international multicenter study, we examined matched primary...
The diverse cellular constituents of childhood brain tumor ependymoma, recently revealed by single cell RNA-sequencing, may underly therapeutic resistance. Here we use spatial transcriptomics to further advance our understanding the microenvironment, mapping subpopulations architecture ependymoma posterior fossa subgroup A (PFA), commonest and most deadly variant.Spatial data from intact PFA sections was deconvoluted resolve histological arrangement neoplastic non-neoplastic types. Key...
Recent autopsy data suggests a high incidence of leptomeningeal metastases (LM), Acta Neuropathologica 2014; 128: 573 and subventricular spread (SVS), 127: 605 in pediatric diffuse intrinsic pontine gliomas, but both LM SVS also occur adult glioblastoma (GBM). Autopsy is required to fully appreciate this tumor behavior.From January 1, 2014 3, 2015 we conducted 239 autopsies, 8 which were identified on search be GBMs.Of these GBMs, one-half showed bulky (SVS (n = 2), bone marrow 1)), 2 4...
Ependymoma (EPN) is a devastating childhood brain tumor. Single-cell analyses have illustrated the cellular heterogeneity of EPN tumors, identifying multiple neoplastic cell states including mesenchymal-differentiated subpopulation which characterizes PFA1 subtype. Here, we characterize immune environment, in context both tumor subtypes and subpopulations using single-cell sequencing (scRNAseq, n = 27), deconvolution bulk gene expression (n 299), spatial proteomics 54), cytokine release...
Abstract Brain tumors are the most common solid tumor in children, and low-grade gliomas (LGGs) childhood brain tumor. Here, we report on 3 patients with LGG harboring previously unreported or rarely reported RAF fusions: FYCO1-RAF1, CTTNBP2-BRAF, SLC44A1-BRAF. We hypothesized that these would show molecular similarity to canonical KIAA1549-BRAF fusion is widely seen alteration pilocytic astrocytoma (PA), pediatric variant, this include mitogen-activated protein kinase (MAPK) pathway...
Plexiform neurofibroma (PN) is a leading cause of morbidity in children with the genetic condition Neurofibromatosis Type 1 (NF1), often disfiguring or threatening vital structures. During formation PN, complex tumor microenvironment (TME) develops, recruitment neoplastic and non-neoplastic cell types being critical for growth progression. Due to cohesive cellularity single-cell RNA-sequencing difficult may result loss detection cellular subpopulations. To bypass this barrier, we performed...
Abstract Pediatric low-grade gliomas (pLGG) comprise 35% of all brain tumors. Despite favorable survival, patients experience significant morbidity from disease and treatments. A deeper understanding pLGG biology is essential to identify novel, more effective, less toxic therapies. We utilized single cell RNA sequencing (scRNA-seq), spatial transcriptomics, cytokine analyses characterize understand tumor immune heterogeneity across pLGG. scRNA-seq revealed cells within the microenvironment...
Abstract BACKGROUND Histiocytic disorders are a group of rare diseases with accumulation macrophages, monocytes, or dendritic cells in various parts the body. ALK-positive histiocytosis is subtype histiocytic neoplasm first described 2008 that very rarely pediatrics. METHODS A 20 month old male presented to an adult hospital after prolonged period headaches, vomiting, and loss developmental milestones. Imaging demonstrated severe hydrocephalus extensive thickened leptomeningeal enhacement...
Abstract Background Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) results from haploinsufficiency the mesenchymal transcription factor FOXF1 gene. To date, only one case an ACDMPV‐causative CNV deletion inherited a very‐low level somatic mosaic mother has been reported. Methods Clinical, histopathological, and molecular studies, including whole genome sequencing, chromosomal microarray analysis, qPCR, Sanger followed by in vitro fertilization (IVF)...
Medulloblastoma (MB) is a heterogeneous disease in which neoplastic cells and associated immune contribute to progression. To better understand cellular heterogeneity MB we profile populations childhood samples using single-cell RNA sequencing, immunohistochemistry deconvolution of transcriptomic data. Neoplastic cluster primarily according individual sample origin part due the effect chromosomal copy number gains losses. Harmony alignment reveals novel subgroup/subtype-associated...
Abstract INTRODUCTION BCL6 corepressor gene (BCOR)-altered glioma brain tumors are a newly identified entity which include cases involving fusion with histone acetyltransferase EP300. Treatment strategies for BCOR-fusion gliomas have not yet been established, largely due to their rarity. In this study we utilize established EP300::BCOR cell line identify effective FDA-approved oncology compounds in vitro. METHODS MAF-1211, from autopsy material, was molecularly defined confirm the and...
Abstract Neuroepithelial tumors with fusion of PLAGL1 or amplification PLAGL1/PLAGL2 have recently been described often ependymoma-like embryonal histology respectively. To further evaluate emerging entities PLAG-family genetic alterations, the histologic, molecular, clinical, and imaging features are for 8 clinical cases encountered at St. Jude ( EWSR1-PLAGL1 n = 6; 1; PLAGL2 1). A histologic feature observed on initial resection in a subset (4/6) supratentorial neuroepithelial...
Tumors are increasingly defined by molecular alterations but approach to cases with discordant histologic and features is unclear. Myxoid glioneuronal tumor (MGNT), histologically similar dysembryoplastic neuroepithelial (DNET), characterized dinucleotide mutations in
Abstract Heterogeneous lymphoproliferative disorders occurring in the post‐transplant setting are considered together as and can rarely present primary cutaneous lesions. These often Epstein–Barr virus‐driven some cases need only be treated with reduction immune suppressive medications. We two of monomorphic disorder, a plasmablastic lymphoma diffuse large B‐cell lymphoma, summarise common reported clinical histopathological features.
Abstract Medulloblastoma (MB) is a heterogeneous disease in which neoplastic cells and associated immune contribute to progression. To better understand cellular heterogeneity MB we use single-cell RNA sequencing, immunohistochemistry deconvolution of transcriptomic data profile populations childhood samples. Neoplastic cluster primarily according individual sample origin part due the effect chromosomal copy number gains losses. Harmony alignment reveals novel subgroup/subtype-associated...
This pediatric case report describes the novel finding of concurrent submental and lingual dermoid cysts, which to our knowledge, has not been previously reported in literature. The etiology cysts involving tongue, floor mouth, neck is varied, representing congenital, inflammatory, neoplastic sources. Dermoid these regions are uncommon most frequently submental, sublingual, spaces. Presenting symptoms vary with cyst size position relative mylohyoid muscle. MRI preferred modality...