A5021775224- Glioma Diagnosis and Treatment
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- RNA Interference and Gene Delivery
- Pancreatic and Hepatic Oncology Research
- Acute Myeloid Leukemia Research
- Chromatin Remodeling and Cancer
- RNA Research and Splicing
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
- Cancer Cells and Metastasis
- Cancer Mechanisms and Therapy
- Immune cells in cancer
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Cancer-related gene regulation
- Cell Adhesion Molecules Research
- Histone Deacetylase Inhibitors Research
- Neuroblastoma Research and Treatments
- Cancer Research and Treatments
- Radiomics and Machine Learning in Medical Imaging
- Cancer Genomics and Diagnostics
Harvard University
2020-2025
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2020-2025
Broad Institute
2020-2025
Dana-Farber Cancer Institute
2020-2024
Arizona Oncology
2023
Boston University
2023
Massachusetts Institute of Technology
2022
Boston Children's Hospital
2020-2021
Washington University in St. Louis
2009-2019
University of Arizona
2008-2010
Abstract Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in diffuse midline gliomas (DMGs) of the childhood pons but are also increasingly recognized adults. Their potential heterogeneity at different ages and locations is vastly understudied. Here, through dissecting single-cell transcriptomic, epigenomic spatial architectures a comprehensive cohort patient H3-K27M DMGs, we delineate how age anatomical location shape glioma cell-intrinsic -extrinsic features light...
Collateral lethality occurs when loss of a gene/protein renders cancer cells dependent on its remaining paralog. Combining genome-scale CRISPR/Cas9 loss-of-function screens with RNA sequencing in over 900 cell lines, we found that cancers nervous system lineage, including adult and pediatric gliomas neuroblastomas, required the nuclear kinase vaccinia-related 1 (VRK1) for their survival vivo. VRK1 dependency was inversely correlated expression paralog VRK2. VRK2 knockout sensitized to loss,...
Abstract Point mutations in the seed sequence of miR-142-3p are present a subset acute myelogenous leukemia (AML) and several subtypes B-cell lymphoma. Here, we show that associated with AML result both loss function decreased miR-142-5p expression. Mir142 altered hematopoietic differentiation multipotent progenitors, enhancing their myeloid potential while suppressing lymphoid potential. During maturation, increased ASH1L protein expression consequently resulted aberrant maintenance Hoxa...
This is a novel case of 16-month-old boy with history prematurity intrauterine growth restriction, severe failure to thrive, microcephaly, pachygyria, agenesis the corpus callosum, and postnatal embolic stroke, who presented new-onset diabetes mellitus diabetic ketoacidosis in setting acute respiratory syndrome coronavirus 2 infection, course complicated by atypical hemolytic (aHUS). patient demonstrated remarkable insulin resistance period before aHUS diagnosis, which resolved first dose...
Pediatric high-grade gliomas (pHGGs) are among the most lethal childhood tumors. While therapeutic approaches were largely adapted from adult treatment regime, significant biological differences between pediatric and exist, which influence immune microenvironment may contribute to limited response current pHGG strategies. We provide a comprehensive transcriptomic analysis of landscape using single-cell RNA sequencing spatial transcriptomics. analyze matched malignant, myeloid, T cells...
TPS4215 Background: GPC3 is an oncofetal protein expressed in 70–80% of HCC and associated with poor prognosis. Preliminary clinical research on GPC3-specific CAR-T treatment has validated as a therapeutic target HCC. Its expression largely confined to the surface tumor cells, making it ideal for TCEs. AZD9793, trispecific IgG1 monoclonal antibody, first-in-class CD8-targeted TCE that directly engages tumor-infiltrating T cells GPC3+ tumors, forming bridge activates leading cell lysis...
A general solid-phase synthetic strategy is developed to prepare fluorescent and/or lanthanide-labeled derivatives of the δ-opioid receptor (δOR) ligand H-Dmt-Tic-Lys(R)-OH. The high δ-OR affinity (Ki = 3 nM) and desirable in vivo characteristics Cy5 derivative 1 suggest its usefulness for structure−function studies localization as a high-contrast noninvasive molecular marker live imaging ex or vivo.
Abstract Multimeric ligands are that contain multiple binding domains simultaneously target cell-surface proteins. Due to cooperative binding, multimeric can have high avidity for cells (tumor) expressing all targeting proteins and only show minimal (normal tissues) none or some of the targets. Identifying combinations targets concurrently express in tumor but not normal is a challenging task. Here, we describe novel approach identifying such using genome-wide gene expression profiling...
MIR233 is genetically or epigenetically silenced in a subset of acute myeloid leukemia (AML). MIR223 normally expressed throughout differentiation and highly hematopoietic stem cells (HSCs). However, the contribution loss to leukemic transformation HSC function largely unknown. Herein, we characterize Mir223 deficient mice. We show that results modest expansion progenitors, but not sufficient induce myeloproliferative disorder. Loss had no discernible effect on quiescence, long-term...
Abstract PDGFRA is commonly altered in pediatric and young adult high-grade gliomas (pHGGs) including histone 3 lysine 27-mutated diffuse midline (H3K27M DMG), a fatal disease with no current options for cure. We performed comprehensive genomic transcriptomic analyses of n=259 glioma cases which revealed alterations ~15% patients. H3K27M DMGs had significantly higher expression compared to H3 wild-type tumors regardless alteration. Tumors gene amplification demonstrated elevated both pHGGs...
Inflammatory myofibroblastic tumor (IMT) is a rare, mesenchymal that has an increased incidence in childhood. Tumors are usually isolated to the chest, abdomen, and retroperitoneum, but metastatic presentations can be seen. Presenting symptoms nonspecific include fever, weight loss, pain, shortness of breath, cough. Approximately 85% IMTs harbor actionable kinase fusions. The diagnosis delayed because overlapping features with inflammatory disorders, such as elevated markers, immunoglobin G...
Abstract Collateral lethality occurs when loss of one paralog renders cancer cells dependent on the remaining paralog. Combining genome scale CRISPR/Cas9 screens coupled with RNA-sequencing in over 900 cell lines, we found that cancers nervous system lineage, including adult and pediatric gliomas neuroblastomas, required nuclear kinase Vaccinia-Related Kinase 1 (VRK1) for their survival. VRK1 dependency was inversely correlated expression its VRK2. VRK2 knockout (KO) sensitized to...