A5070637040- Glioma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Cell Image Analysis Techniques
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Multiple Myeloma Research and Treatments
- Genomic variations and chromosomal abnormalities
- Chromatin Remodeling and Cancer
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Genomics and Phylogenetic Studies
- CRISPR and Genetic Engineering
- Neurogenesis and neuroplasticity mechanisms
- Chromosomal and Genetic Variations
- Alzheimer's disease research and treatments
- Cancer Mechanisms and Therapy
- Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- Lysosomal Storage Disorders Research
- Mosquito-borne diseases and control
- Autophagy in Disease and Therapy
- Extracellular vesicles in disease
- Health Services Management and Policy
- Healthcare Systems and Challenges
Allen Institute for Brain Science
2023
Brown University
2022-2023
Broad Institute
2016-2022
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2016-2022
Dana-Farber Cancer Institute
2016-2021
John Brown University
2020
Binghamton University
2018
Boston Children's Hospital
2016
Brigham and Women's Hospital
2016
Harvard University
2016
Structural variants (SVs), including small insertion and deletion (indels), are challenging to detect through standard alignment-based variant calling methods. Sequence assembly offers a powerful approach identifying SVs, but is difficult apply at scale genome-wide for SV detection due its computational complexity the difficulty of extracting SVs from contigs. We describe SvABA, an efficient accurate method detecting short-read sequencing data using local with low memory computing...
Chitinase-3-like protein 1 (CHI3L1/YKL-40) has long been known as a biomarker for early detection of neuroinflammation and disease diagnosis Alzheimer's (AD). In the brain, CHI3L1 is primarily provided by astrocytes heralds reactive, neurotoxic state triggered inflammation other stress signals. However, how acts in or it contributes to AD relevant neurodegenerative conditions remains unknown. peripheral tissues, our group others have uncovered that master regulator wide range injury repair...
Clinical genomics platforms are needed to identify targetable alterations, but implementation of these technologies and best practices in routine clinical pediatric oncology practice not yet well established.Profile is an institution-wide prospective research initiative that uses targeted sequencing alterations tumors. OncoPanel, a multiplexed exome-sequencing platform includes 300 cancer-causing genes, was used assess single nucleotide variants rearrangements/indels. Alterations were...
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 Background Many biological processes, such as cancer metastasis, organismal development, and acquisition of resistance to cytotoxic therapy, rely on the emergence rare sub-clones from a larger population. Understanding how genetic epigenetic features diverse clones affect clonal fitness provides insight into molecular mechanisms underlying selective processes. While large-scale barcoding with NGS readout has facilitated cellular assessment at population level, this approach does not...
Abstract JC polyomavirus (JCPyV) is a small, non‐enveloped virus that persists in the kidney about half adult population. In severely immune‐compromised individuals JCPyV causes neurodegenerative disease progressive multifocal leukoencephalopathy (PML) brain. has been shown to infect cells by both direct and indirect mechanisms, latter involving extracellular vesicle (EV) mediated infection. While mechanisms of infection are well studied EV poorly understood. Using combination chemical...
Abstract Structural variants (SVs), including small insertion and deletion (indels), are challenging to detect through standard alignment-based variant calling methods. Sequence assembly offers a powerful approach identifying SVs, but is difficult apply at-scale genome-wide for SV detection due its computational complexity the difficulty of extracting SVs from contigs. We describe SvABA, an efficient accurate method detecting short-read sequencing data using local with low memory computing...
In Alzheimer's disease (AD) and other neurodegenerative disorders, oligodendroglial failure is a common early pathological feature, but how it contributes to development progression, particularly in the gray matter of brain, remains largely unknown. The dysfunction oligodendrocyte lineage cells hallmarked by deficiencies myelination impaired self-renewal precursor (OPCs). These two defects are caused at least part disruption interactions between neuron oligodendrocytes along buildup...
Abstract Background Many biological processes, such as cancer metastasis, organismal development, and development of resistance to cytotoxic therapy, rely on the emergence rare sub-clones from a larger population. Understanding how genetic epigenetic features diverse clones affect clonal fitness provides insight into molecular mechanisms underlying selective processes. However, identifying causal drivers remains challenging. Population-level analysis has limited resolution characterize prior...
In Alzheimer's disease (AD) and other neurodegenerative disorders, oligodendroglial failure is a common early pathological feature, but how it contributes to development progression, particularly in the gray matter of brain, remains largely unknown. The dysfunction oligodendrocyte lineage cells hallmarked by deficiencies myelination impaired self-renewal precursor (OPCs). These two defects are caused at least part disruption interactions between neuron oligodendrocytes along buildup...
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...
INTRODUCTION: Clinical genomics platforms identify targetable alterations for precision medicine in pediatric neuro-oncology, allowing both the genomic profiling of tumors to inform clinical care and facilitating potential discovery novel driver alterations. METHODS: We applied two (OncoPanel OncoCopy) profile brain a setting. OncoPanel, multiplexed targeted exome-sequencing platform that includes 300 cancer causing genes, was used assess single nucleotide variants rearrangements/indels....
INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) remains a devastating and incurable disease. The DIPG-BATs clinical trial incorporates diagnostic biopsy with molecularly determined treatment stratification. Here we present the initial genomic analysis of cohort. METHODS: Children enrolled on underwent upfront biopsies prior to commencement therapy. RNA DNA were extracted from single core subjected whole-genome sequencing (WGS) RNA-sequencing. Tumor samples also collected at autopsy if...
Abstract BACKGROUND Driver single nucleotide variants (SNV) and somatic copy number aberrations (SCNA) of pediatric high-grade glioma (pHGGs), including Diffuse Midline Gliomas (DMGs) are characterized. However, structural (SVs) in pHGGs the mechanisms through which they contribute to formation have not been systematically analyzed genome-wide. METHODS Using SvABA for SVs as well latest pipelines SCNAs SNVs we whole-genome sequencing from 174 patients. This includes 60 previously unpublished...
INTRODUCTION: Children with MYC-amplified medulloblastoma face a dismal prognosis. We have previously found BET-bromodomain inhibition to preclinical promise as therapeutic strategy for medulloblastoma. However, the mechanisms of action these inhibitors not been fully elucidated. In addition, development resistance is likely impact their clinical efficacy. To address this, we characterized cancer cell evolution in response models. METHODS: applied genome wide over-expression (ORF) and...
Emotionally arousing images produce a transient accuracy impairment for detecting neutral targets under conditions of stringent spatiotemporal competition (e.g., rapid serial visual presentation). This performance has been termed emotion-induced blindness and previous studies have demonstrated that the magnitude time course this processing is exaggerated in individuals with clinical anxiety disorders. Here, we tested whether effect can be modulated by anxious anticipation healthy sample...
BACKGROUND: BET-bromodomain proteins bind to H3K27ac enhancers and recruit transcriptional facilitate the expression of genes. Inhibition shows preclinical promise for MYC-driven tumors such as medulloblastoma (MB), however mechanism action means resistance are not well described. We hypothesized that genes required MB cell growth were sufficient rescue effects inhibition (BETi) would signify key downstream effectors this class inhibitors. METHODS: applied an integrative genomics approach:...
BET-bromodomain inhibition (BETi) has shown pre-clinical promise for MYC-amplified medulloblastoma. However, the mechanisms its action, and ultimately of resistance, have not been fully defined. Using a combination expression profiling, genome-scale CRISPR/Cas9-mediated loss function ORF/cDNA-driven rescue screens, cell-based models spontaneous we identified bHLH/homeobox transcription factors including NEUROD1, NEUROG1 NEUROG3, cell-cycle regulators CCND2 CCND3 as key gene mediators BETi’s...