A5048399682- Glioma Diagnosis and Treatment
- Lung Cancer Research Studies
- Neuroendocrine Tumor Research Advances
- Neuroblastoma Research and Treatments
- Adenosine and Purinergic Signaling
- Cancer-related Molecular Pathways
- Protein Degradation and Inhibitors
- Neuroinflammation and Neurodegeneration Mechanisms
- Lung Cancer Treatments and Mutations
- Cancer-related molecular mechanisms research
- Circular RNAs in diseases
- Multiple Myeloma Research and Treatments
- Adrenal and Paraganglionic Tumors
- Cancer Research and Treatments
- RNA modifications and cancer
- Nanoplatforms for cancer theranostics
- Pituitary Gland Disorders and Treatments
- Extracellular vesicles in disease
- Genomics and Chromatin Dynamics
- Human Health and Disease
- Single-cell and spatial transcriptomics
- Ubiquitin and proteasome pathways
- PARP inhibition in cancer therapy
- 14-3-3 protein interactions
- Breast Cancer Treatment Studies
Broad Institute
2016-2022
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2020-2022
Harvard University
2019-2022
Dana-Farber Cancer Institute
2019-2022
Mayo Clinic
2018
Manmohan Memorial Institute of Health Sciences
2018
Carleton College
2015
How the glioma immune microenvironment fosters tumorigenesis remains incompletely defined. Here, we use single-cell RNA-sequencing and multiplexed tissue-imaging to characterize composition, spatial organization, clinical significance of extracellular purinergic signaling in glioma. We show that microglia are predominant source CD39, while tumor cells principally express CD73. In glioblastoma, CD73 is associated with EGFR amplification, astrocyte-like differentiation, increased adenosine,...
Abstract The role of PPM1D mutations in de novo gliomagenesis has not been systematically explored. Here we analyze whole genome sequences 170 pediatric high-grade gliomas and find that truncating increase the stability its phosphatase are clonal driver events 11% Diffuse Midline Gliomas (DMGs) enriched primary pontine tumors. Through development DMG mouse models, show potentiate activity is required for vivo oncogenesis. Finally, apply integrative phosphoproteomic functional genomics assays...
Abstract Purpose: Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, comprise 30% malignancies, and are defined histologically as typical (TC) atypical (AC) tumors. The role specific genomic alterations the pathogenesis pulmonary remains poorly understood. We sought identify pathways that deregulated these find novel therapeutic targets Experimental Design: performed integrated analysis comprising whole genome exome sequencing, mRNA expression profiling SNP...
Abstract Pilocytic astrocytoma (PA), the most common childhood brain tumor, is a low-grade glioma with single driver BRAF rearrangement. Here, we perform scRNAseq in six PAs using methods that enabled detection of When compared to higher-grade gliomas, strikingly higher proportion PA cancer cells exhibit differentiated, astrocyte-like phenotype. A smaller progenitor-like phenotype evidence proliferation. These express mitogen-activated protein kinase (MAPK) programme was absent from gliomas....
Abstract Aneuploidy and copy-number alterations (CNAs) are a hallmark of human cancer. Although genetically engineered mouse models (GEMMs) commonly used to model cancer, their chromosomal landscapes remain underexplored. Here we use gene expression profiles infer CNAs in 3,108 samples from 45 models, providing the first comprehensive catalogue aberrations cancer GEMMs. Mining this resource, find that most accumulate late during breast tumorigenesis, observe marked differences CNA prevalence...
BET-bromodomain inhibition (BETi) has shown pre-clinical promise for MYC-amplified medulloblastoma. However, the mechanisms its action, and ultimately resistance, have not been fully defined. Here, using a combination of expression profiling, genome-scale CRISPR/Cas9-mediated loss function ORF/cDNA driven rescue screens, cell-based models spontaneous we identify bHLH/homeobox transcription factors cell-cycle regulators as key genes mediating BETi's response resistance. Cells that acquire...
ABSTRACT Glioblastoma develops an immunosuppressive microenvironment that fosters tumorigenesis and resistance to current therapeutic strategies. Here we use multiplexed tissue imaging single-cell RNA-sequencing characterize the composition, spatial organization, clinical significance of extracellular purinergic signaling in glioblastoma. We show glioblastoma exhibit strong expression CD39 CD73 ectoenzymes, correlating with increased adenosine levels. Microglia are predominant source CD39,...
Background: Poisoning is one of the leading causes morbidity and mortality in Nepal also a major public health problem worldwide. It needs specific epidemiological surveillance to determine extent pattern poisoning place, take preventive measures. Hence this study aimed explore demographic, etiological, clinical characteristics cases MMTH assess effect variables such as age, sex, agent frequency.Methods: A retrospective, descriptive, unicentric semi-quantitative was conducted year 2074 at...
Abstract Pediatric high-grade gliomas (pHGGs), encompassing hemispheric and diffuse midline (DMGs), remain a devastating disease. The last decade has revealed oncogenic drivers including single nucleotide variants (SNVs) in histones. However, the contribution of structural (SVs) to gliomagenesis not been systematically explored due limitations early SV analysis approaches. Using algorithms, we recently created, analyzed SVs whole-genome sequences 179 pHGGs novel cohort treatment naïve...
Abstract INTRODUCTION Adamantinomatous craniopharyngiomas (ACPs) are characterized by activating mutations in the CTNNB1 gene. Here we perform a comprehensive genomic analysis of 23 ACPs to define landscape alterations this disease. METHODS We performed whole-genome sequencing 24 and their matched normal tissues. used Mutect 2.0 detect indels these samples MutSig2CV identify significant mutations. Copy numbers were called using GATK4 pipeline GISTIC was applied alterations. Finally, SvABA...
Abstract Aneuploidy and large copy number alterations (CNAs) are a hallmark of human cancer. Although genetically engineered mouse models (GEMMs) commonly used to model cancer, their chromosomal landscape remains largely unexplored because large-scale CNA data have not been generated. Here we gene expression profiles infer CNAs in 3,108 samples from 45 models, providing the first comprehensive catalog aberrations cancer GEMMs. Mining this expansive resource, found that most accumulated late...
Abstract Introduction: Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, and comprise 30% malignancies. They are defined histologically as typical (TC) atypical (AC) tumors, characterized by neuroendocrine differentiation the potential metastasize. Method: We genomic alterations pulmonary using whole genome exome sequencing addition mRNA expression SNP genotyping from specimens normal lung, carcinoid, SCLC. Results: Analysis data identified novel mutations...
<p>Supplemental legend</p>
<p>Table S1: Clinicopathologic features Table S2: Statistical analysis of correlation between number mutations with sevaral clinical characteristics S3: List copy variations in different types pulmonary neuroendocrine tumors as reported by studies. Lung typical carcinoid (TC), atypical S4: S2. genes differentially expressed regions corresponding variation (red signifies amplification and blue represent deletion) S5: Functional using the DAVID functional annotation database S6: A table...
<p>Pathway analysis of significantly mutated genes</p>
<div>Abstract<p><b>Purpose:</b> Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, comprise 30% malignancies, and are defined histologically as typical (TC) atypical (AC) tumors. The role specific genomic alterations the pathogenesis pulmonary remains poorly understood. We sought identify pathways that deregulated these find novel therapeutic targets tumors.</p><p><b>Experimental Design:</b> performed integrated...
<div>Abstract<p><b>Purpose:</b> Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, comprise 30% malignancies, and are defined histologically as typical (TC) atypical (AC) tumors. The role specific genomic alterations the pathogenesis pulmonary remains poorly understood. We sought identify pathways that deregulated these find novel therapeutic targets tumors.</p><p><b>Experimental Design:</b> performed integrated...
<p>Table S1: Clinicopathologic features Table S2: Statistical analysis of correlation between number mutations with sevaral clinical characteristics S3: List copy variations in different types pulmonary neuroendocrine tumors as reported by studies. Lung typical carcinoid (TC), atypical S4: S2. genes differentially expressed regions corresponding variation (red signifies amplification and blue represent deletion) S5: Functional using the DAVID functional annotation database S6: A table...
<p>Supplemental legend</p>
<p>Pathway analysis of significantly mutated genes</p>
Diffuse Intrinsic Pontine Gliomas (DIPGs) are universally fatal. Effective treatments desperately needed. DIPGs harbor histone K27M mutations (H3F3A or HIST1H3B) and also alterations that lead to growth factor receptor activation (such as PDGFRA amplification). We others have found recurrent truncating PPM1D mutation (PPM1Dtr) in up 20% of all DIPGs, they mutually exclusive with TP53 mutations. hypothesized sufficient induce oncogenesis necessary for DIPG proliferation, therefore represent a...
Abstract BACKGROUND Diffuse intrinsic pontine gliomas (DIPGs) pose particular challenges for treatment. We recently completed a genomic analysis of close to 200 DIPGs and high-grade gliomas. identified that nearly 10% all have increased expression the fork head domain transcription factor FOXR2. hypothesize FOXR2 accelerates gliomagenesis in histone mutant represents previously unexplored therapeutic target. METHODS To determine whether is sufficient mediate gliomagenesis, we applied an...