McKenzie Shaw
A5017320240- Glioma Diagnosis and Treatment
- Single-cell and spatial transcriptomics
- Click Chemistry and Applications
- Synthesis and Biological Evaluation
- Radiopharmaceutical Chemistry and Applications
- MicroRNA in disease regulation
- Chromatin Remodeling and Cancer
- Extracellular vesicles in disease
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Alzheimer's disease research and treatments
- Protein Degradation and Inhibitors
- Ferroptosis and cancer prognosis
- Brain Metastases and Treatment
- Cancer Mechanisms and Therapy
- Peptidase Inhibition and Analysis
- Bioinformatics and Genomic Networks
- 14-3-3 protein interactions
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Radiomics and Machine Learning in Medical Imaging
- Cell Image Analysis Techniques
Broad Institute
2017-2025
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2019-2025
Dana-Farber Cancer Institute
2020-2024
Harvard University
2017-2023
Boston University
2023
Boston Children's Hospital
2023
Center for Cancer Research
2017-2022
Massachusetts General Hospital
2016-2022
Cleveland Clinic Lerner College of Medicine
2015-2018
Cleveland Clinic
2016-2017
Tumor subclasses differ according to the genotypes and phenotypes of malignant cells as well composition tumor microenvironment (TME). We dissected these influences in isocitrate dehydrogenase (IDH)-mutant gliomas by combining 14,226 single-cell RNA sequencing (RNA-seq) profiles from 16 patient samples with bulk RNA-seq 165 samples. Differences between IDH-mutant astrocytoma oligodendroglioma can be primarily explained distinct TME signature genetic events, whereas both types share similar...
Gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) arise primarily in the midline of central nervous system young children, suggesting a cooperation between genetics and cellular context tumorigenesis. Although H3K27M-glioma are well characterized, their architecture remains uncharted. We performed single-cell RNA sequencing 3321 cells from six primary matched models. found that contain resemble oligodendrocyte precursor (OPC-like), whereas more differentiated malignant...
Recent advances in single-cell, transcriptomic profiling have provided unprecedented access to investigate cell heterogeneity during tissue and organ development. In this study, we used massively parallel, single-cell RNA sequencing define within the zebrafish kidney marrow, constructing a comprehensive molecular atlas of definitive hematopoiesis functionally distinct renal cells found adult zebrafish. Because our method analyzed blood an unbiased manner, approach was useful characterizing...
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...
Diffuse hemispheric gliomas, H3G34R/V-mutant (DHG-H3G34), are lethal brain tumors lacking targeted therapies. They originate from interneuronal precursors; however, leveraging this origin for therapeutic insights remains unexplored. Here, we delineate a cellular hierarchy along the interneuron lineage development continuum, revealing that DHG-H3G34 mirror spatial patterns of progenitor streams surrounding nests, as seen during human development. Integrating these findings with genome-wide...
Melanoma-derived brain metastases (MBM) represent an unmet clinical need because central nervous system progression is frequently end stage of the disease. Immune checkpoint inhibitors (ICI) provide a opportunity against MBM; however, MBM tumor microenvironment (TME) has not been fully elucidated in context ICI. To dissect unique elements TME and correlates response to ICI, we collected 32 fresh performed single-cell RNA sequencing T-cell receptor clonotyping on T cells from matched blood...
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...
Abstract BACKGROUND Atypical teratoid rhabdoid tumors (ATRTs) remain a significant clinical challenge in pediatric neurooncology. Despite the simplicity of genomic profile, mostly characterized by functional loss SMARCB1 and rare cases SMARCA4, ATRTs are molecularly epigenetically diverse, with three main molecular subgroups identified: ATRT-TYR, ATRT-SHH ATRT-MYC. METHODS To address lack effective mechanism-of-action based treatments comprehend biology these subgroups, we conducted 10X...
Abstract Histone 3 lysine27-to-methionine mutations (H3-K27M) frequently occur in childhood diffuse midline gliomas (DMGs) of the pons, thalamus, and spinal cord, presumed to be driven by specific spatiotemporal context these locations during postnatal development. While most common pons at mid-childhood ages, same oncohistone mutation is recurrently detected adult DMGs throughout different regions. The potential heterogeneity tumors ages anatomical are vastly understudied. Through...
Abstract Supratentorial ependymomas are aggressive childhood brain cancers that retain features of neurodevelopmental cell types and segregate into molecularly clinically distinct subgroups, suggesting different developmental roots. The signatures as well microenvironmental factors underlying aberrant cellular transformation behavior across each supratentorial ependymoma subgroup unknown. Here we integrated single cell- spatial transcriptomics, in vitro vivo live-cell imaging to define...
Abstract Supratentorial ependymomas (ST-EPN) are aggressive pediatric brain tumors that categorized into distinct molecular subgroups. However, the developmental origins, tumor microenvironment, and phenotypic characteristics of subpopulations across these subgroups still poorly understood. In this study, we explored human signatures, global spatial organization, morphological migratory cell state behaviors in ST-EPN at unprecedented resolution. We profiled 42 patients encompassing ZFTA-RELA...
Evidence suggests that Fyn, a tyrosine kinase, may be involved in aberrant tau phosphorylation AD and is elevated brain compared to controls. Extracellular oligomeric Aβ, cellular prion protein Fyn coupling are implicated an intracellular signaling cascade which turn influence expression. Our previous study found association between SNP the 5’ region of FYN cerebrospinal fluid (CSF) levels suggesting regulatory genetic content play role CSF tau. Since it has been proposed expression might...
Multiple regulatory elements have been described at the APOE locus. These influence gene expression according to cell type. Little is known about of miRNA post-transcriptional regulation this We recently that are predicted target as differentially modulated in AD post-mortem brain compared controls. However, given tissue a mix multiple types, we wondered if targeting APOE3’UTR might be type specific. The aim investigation was demonstrate 3’UTR influences promoter activity human lines were...
Tau phosphorylation is under the control of multiple kinases and phosphatases, including GSK3β, Fyn, PP2A. Previously, our group correlated two regulatory region single nucleotide polymorphisms (SNPs) in FYN gene as associated with increased hyperphosphorylated tau levels. In this study, we hypothesized that expression brain directly influenced by AD status genetic content. Brain samples cerebellum hippocampus were taken from patients late-onset (n = 21) cognitively normal controls 22),...
Accumulating evidence in Alzheimer’s Disease (AD) research suggests that alterations microRNA (miRNA) expression is associated with disease pathology. Our previous studies show promoter haplotype of ADAM10 which encodes the major α-secretase responsible for cleaving Amyloid Precursor Protein with: (1) higher CSF sAPP α levels cognitively normal controls compared AD patients, (2) postmortem brain hippocampus, but not cerebellum, protein subjects low plaque scores those high scores, and (3)...
While human tumors are shaped by the genetic evolution of cancer cells, evidence also suggests that they display superimposed hierarchies reminiscent normal development. Yet, relating and hierarchical models organization has been limited technical challenges. Here, studying hemispheric midline pediatric adult glioblastomas, we profiled thousands single cells from fresh RNA-seq reconstructed epigenetic cellular architecture in patients. We identified most differentiated along specialized...