John J. Y. Lee
A5049171513- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Cancer Genomics and Diagnostics
- Computational Drug Discovery Methods
- Cell Image Analysis Techniques
- Hedgehog Signaling Pathway Studies
- Hematopoietic Stem Cell Transplantation
- Genetics and Neurodevelopmental Disorders
- T-cell and B-cell Immunology
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Vascular Procedures and Complications
- Viral gastroenteritis research and epidemiology
- Developmental Biology and Gene Regulation
- Renal and related cancers
- Fetal and Pediatric Neurological Disorders
- Biomedical Ethics and Regulation
- Cancer-related molecular mechanisms research
- Protein Degradation and Inhibitors
- Ultrasound and Hyperthermia Applications
- Cancer, Hypoxia, and Metabolism
University of California, San Diego
2020-2025
University of Toronto
2014-2025
Hospital for Sick Children
2016-2025
SickKids Foundation
2016-2025
Harvard University
2023-2025
Massachusetts General Hospital
2023-2025
Broad Institute
2023-2025
Massachusetts Institute of Technology
2023-2025
Center for Cancer Research
2023-2025
Brain Tumour Research
2020
A subset of patients with IDH-mutant glioma respond to inhibitors mutant IDH (IDHi), yet the molecular underpinnings such responses are not understood. Here, we profiled by single-cell or single-nucleus RNA-sequencing three oligodendrogliomas from who derived clinical benefit IDHi. Importantly, tissues were sampled on-drug, four weeks treatment initiation. We further integrate our findings analysis and bulk transcriptomes independent cohorts experimental models. find that IDHi induces a...
Abstract Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) have revolutionized breast cancer therapy. However, <50% of patients an objective response, nearly all develop resistance during To elucidate the underlying mechanisms, we constructed interpretable deep learning model response to palbociclib, a CDK4/6i, based on reference map multiprotein assemblies in cancer. The identifies eight core that integrate rare common alterations across 90 genes stratify palbociclib-sensitive versus...
Abstract Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers the developing central nervous system. Here, we use unbiased sequencing transcriptome across large cohort 250 tumors to reveal differences among molecular subtypes disease, demonstrate previously unappreciated importance non-coding RNA transcripts. We identify alterations within cAMP dependent pathway ( GNAS , PRKAR1A ) which converge on GLI2 activity show that 18% have genetic event...
A major goal of cancer research is to understand how mutations distributed across diverse genes affect common cellular systems, including multiprotein complexes and assemblies. Two challenges—how comprehensively map such systems identify which are under mutational selection—have hindered this understanding. Accordingly, we created a comprehensive protein integrating both new published multi-omic interaction data at multiple scales analysis. We then developed unified statistical model that...
Posterior fossa group A (PFA) ependymoma is a lethal brain cancer diagnosed in infants and young children. The lack of driver events the PFA linear genome led us to search its 3D for characteristic features. Here, we reconstructed genomes from diverse childhood tumor types uncovered global topology that highly reminiscent stem progenitor cells variety human tissues. remarkable feature exclusively present are type B ultra long-range interactions PFAs (TULIPs), regions separated by great...
Abstract Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% G4 medulloblastoma). In contrast, highly similar SHH distinct diametrically opposed gain-of-function mutations copy number gains (20% Overexpression...
Abstract Coronary artery compression is a rare and potentially fatal complication after pulmonary valve replacement. This report describes myocardial infarction from extrinsic left main coronary replacement in 10‐y‐old boy. He was successfully treated with percutaneous intervention. © 2006 Wiley‐Liss, Inc.
Concomitant valvular and abdominal aortic pathologies, both requiring urgent surgical interventions, are an uncommon entity. The ideal management of such a scenario varies, depending on host variables. Due to its complexity rarity, the approach remains unknown. We describe patient who presents with delayed diagnosis concomitant Salmonella species mitral valve (MV) endocarditis mycotic aneurysm (AAA). Though clinical entities required intervention, presence one made intervening for other...
The composition of commensal bacteria plays a critical role in controlling immune responses the intestine. Studies have shown that specific bacterial strains may capacity to enhance host defense against gastrointestinal viral infections. While norovirus is known be most common cause gastroenteritis, leading an estimated 200,000 deaths every year, identification with protective effects infection remains elusive. Here, we discovered
Medulloblastoma is the most common type of malignant pediatric brain tumor with group 4 medulloblastomas (G4 MBs) accounting for 40% cases. However, molecular mechanisms that underlie this subgroup are still poorly understood. Point mutations detected in a large number genes at low incidence per gene while detection complex structural variants recurrently affected typically requires application long-read technologies.Here, we applied linked-read sequencing, which combines long-range genome...
Life-long blood production requires long-term hematopoietic stem cells (LT-HSC) - marked by stemness states involving quiescence and self-renewal to transition into activated short-term HSC (ST-HSC) with reduced stemness. As few transcriptional changes underlie this transition, we used single-cell bulk ATAC-seq on human stem/progenitor subsets (HSPC) uncover chromatin accessibility signatures, one including LT-HSC (LT/HSPC signature) another excluding (Act/HSPC signature). These signatures...
Polycomb Repressive Complex 2 (PRC2)-mediated histone H3K27 tri-methylation (H3K27me3) recruits canonical PRC1 (cPRC1) to maintain heterochromatin. In early development, polycomb-regulated genes are connected through long-range 3D interactions which resolve upon differentiation. Here, we report that polycomb looping is controlled by H3K27me3 spreading and regulates target gene silencing cell fate specification. Using glioma-derived H3 Lys-27-Met (H3K27M) mutations as tools restrict...
Four main medulloblastoma (MB) molecular subtypes have been identified based on transcriptional, DNA methylation, and genetic profiles. However, it is currently not known whether 3D genome architecture differs between MB subtypes. To address this question, we performed in situ Hi-C to reconstruct the of In total, generated matching transcriptome data for 28 surgical specimens one patient-derived xenograft. The average resolution maps was 6,833 bp. Using these data, found that insulation...