A5060358208- Glioma Diagnosis and Treatment
- FOXO transcription factor regulation
- Neuroblastoma Research and Treatments
- Ferroptosis and cancer prognosis
- Renal and related cancers
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Health and Medical Research Impacts
- Cancer-related molecular mechanisms research
- Doctoral Education Challenges and Solutions
- Single-cell and spatial transcriptomics
- Career Development and Diversity
- Circular RNAs in diseases
- Ubiquitin and proteasome pathways
- Lung Cancer Treatments and Mutations
- Diversity and Career in Medicine
- Advanced Electron Microscopy Techniques and Applications
- Biomedical and Engineering Education
- Circadian rhythm and melatonin
- Innovations in Medical Education
- Sleep and Wakefulness Research
- Childhood Cancer Survivors' Quality of Life
- Photoreceptor and optogenetics research
- Adrenal and Paraganglionic Tumors
- Interdisciplinary Research and Collaboration
Children's Hospital of Los Angeles
2024-2025
University of Southern California
2024-2025
Broad Institute
2020-2024
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2020-2024
Dana-Farber Cancer Institute
2004-2023
German Cancer Research Center
2023
Hopp Children's Cancer Center Heidelberg
2023
Heidelberg University
2023
Sabin Vaccine Institute
2023
University of Cincinnati
2023
Analyses in mice deficient for the blue-light-sensitive photopigment melanopsin show that direct effects of light on behavior and EEG depend time day. The data further suggest an unexpected role sleep homeostasis.
Introdução: O preenchimento do Formulário da Autoavaliação das Práticas de Segurança Paciente elaborado pela Anvisa é realizado forma voluntária e anual serviços saúde com leitos UTI envolve a avaliação indicadores estrutura processo, baseada na Resolução Diretoria Colegiada nº 36, 25 julho 2013. Objetivo: Analisar o processo autoavaliação nacional sob óptica vigilância, no período 2016 2019. Método: Realizou-se um estudo retrospectivo, análise documental qual foram analisadas comparadas as...
Abstract The accumulation of somatic DNA mutations over time is a hallmark aging in many dividing and nondividing cells but has not been studied postmitotic human cardiomyocytes. Using single-cell whole-genome sequencing, we identified characterized the landscape single-nucleotide variants (sSNVs) 56 single cardiomyocytes from 12 individuals (aged 0.4 to 82 years). Cardiomyocyte sSNVs accumulate with age at rates that are faster than cell types neurons. show distinctive mutational signatures...
The prognosis for patients with pediatric high-grade glioma (pHGG) is poor despite aggressive multimodal therapy. Objective responses to targeted therapy BRAF inhibitors have been reported in some recurrent BRAF-mutant pHGG but are rarely sustained.
Abstract Background Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and a mitogen-activated protein kinase (MAPK)-driven disease. Oncogenic MAPK-signaling drives majority of cells into oncogene-induced senescence (OIS). While OIS induces resistance to antiproliferative therapies, it represents potential vulnerability exploitable by senolytic agents. Methods We established new patient-derived PA cell lines that preserve molecular features primary tumors can be studied in...
Abstract The mammalian cerebral cortex shows functional specialization into regions with distinct neuronal compositions, most strikingly in the human brain, but little is known about how cellular lineages shape cortical regional variation and cell types during development. Here, we use somatic single nucleotide variants (sSNVs) to map of sub-types regions. Early-occurring sSNVs rarely respect Brodmann area (BA) borders, while late-occurring mark neuron-generating clones modest restriction,...
<p>Bulk RNAseq projections by ssGSEA.</p>
<p>Orthotopic engraftment of cell lines derived from Foxr2 p53LOF murine model.</p>
<p><i>Foxr2</i> is oncogenic in the ventral telencephalon mice. <b>A,</b> Schematic describing IUE-based strategy to model <i>FOXR2</i>-driven brain tumors. PiggyBac and CRISPR vectors are delivered into neural stem cells GEs at E12.5. After birth, mice develop tumors euthanized when neurologic symptoms become apparent. <b>B,</b> Representative brightfield (BF) fluorescence (GFP) images of a GFP+ <i>Foxr2</i>-driven tumor...
<p>Foxr2 chromatin binding sites in <i>Foxr2</i> p53<sup>LOF</sup> neurosphere show enrichment ETS and glial pathways. <b>A,</b> Validation of FOXR2 overexpression p53 downregulation <i>ex vivo</i><i>Foxr2</i> neurospheres by qRT-PCR. <b>B,</b> <i>Nkx2-1</i>, <i>Lhx6</i>, <i>Dlx5</i>, <i>Dlx6</i>, <i>Emx2</i>, <i>Sox10</i>,...
<p><i>FOXR2</i> does not induce expression of MGE or EC-NB TFs. <b>A,</b> Bulk RNA-seq telencephalon patterning Top and third rows, tumor samples from this study cohort. Second row, (Gartlgruber colleagues, ref. <a href="#bib21" target="_blank">21</a>) subset to high risk, stage 4 with <i>FOXR2</i> (normalized >2). Bottom H9 human NSCs transduced HA-FOXR2 controls HcRed (Tsai href="#bib7" target="_blank">7</a>). All box plots...
<p>Mouse models transcriptomically recapitulate human NB-FOXR2. <b>A,</b> Heatmap showing CNVs in <i>Foxr2</i> p53<sup>LOF</sup> and alone models, computed with inferCNV. <b>B,</b> Top, Uniform Manifold Approximation Projection (UMAP) joint representation of mouse model single-cell datasets (<i>n</i> = 3) without integration or batch correction. Cells colored by broad cell class derived from automated type annotation,...
<p>NB-FOXR2 tumors transcriptionally resemble interneurons and OPC cells. <b>A,</b><i>t</i>-Distributed stochastic neighbor embedding (<i>t</i>-SNE) of bulk RNA-seq profiles pediatric brain (left) with stage 4 high-risk EC-NBs from Gartlgruber colleagues (ref. <a href="#bib21" target="_blank">21</a>; right) using ssGSEA scores for <i>N</i> = 374 cell type–specific gene signatures reference scRNA-seq datasets....
<p>Quality control (QC) metrics and copy-number variation for scRNAseq datasets of NB-FOXR2 patient tumors.</p>