Howard Y. Chang

A mitotic restriction point for extrachromosomal DNA hubs in cancer cells

This study identifies mitosis as a critical window for ecDNA hub organization in cancer cells and shows WEE1 regulates hub integrity and oncogene expression.

Inverted logic of ecDNA localization converts nuclear periphery into oncogenic transcription hubs in cancer

The paper shows ecDNA localizes to the nuclear periphery in cancer, resisting silencing and enhancing transcriptional output through interactions with the nuclear lamina.

Regulation of immune signal integration and memory by inflammation-induced chromosome conformation

This study shows that inflammation-induced changes in 3D genome conformation regulate immune signal integration and transcriptional memory in macrophages.

Spatiotemporal lineage tracing reveals the dynamic spatial architecture of tumor growth and metastasis

This study uses spatial transcriptomics and lineage tracing to show how tumor subclones drive microenvironmental changes that promote metastasis in a mouse model.

Somatic mutations reveal the ontogeny of human microglia

This study uses somatic mutations to track marrow-derived cell infiltration into the human brain, finding widespread microglia replenishment and a protective link between clonal hematopoiesis and Alzheimer's disease.

Fast and accurate resolution of ecDNA sequence using Cycle-Extractor

Cycle-Extractor accurately reconstructs ecDNA structures from both short- and long-read sequencing data, outperforming existing methods in speed and completeness.

Lipid Nanoparticles for Spleen-Targeted RNA delivery

This study develops lipid nanoparticles (LNPs) for spleen-targeted RNA delivery without altering charge, showing improved splenic accumulation and distinct transcriptomic effects compared to conventional LNPs.

Dynamic optimization of extrachromosomal DNA copy number drives tumour evolution

This study shows ecDNA copy number plasticity drives tumour evolution by generating functional heterogeneity and promoting drug resistance.

scAmp analyzes focal gene amplifications at single-cell resolution

scAmp detects and analyzes ecDNA at single-cell resolution, showing its impact on chromatin accessibility in cancer cells.

Deep learning-guided design of cell type-specific AAV promoters

This study designs cell type-specific AAV promoters using deep learning, outperforming rational approaches in mouse retinal cells and showing promise for human applications.

Reconstructing the three-dimensional architecture of extrachromosomal DNA with ec3D

The paper introduces ec3D, a method to reconstruct 3D structures of ecDNA from Hi-C data, revealing spherical configurations and unique long-range interactions in cancer.

Genetic elements promote retention of extrachromosomal DNA in cancer cells

A genome-wide plasmid screen, Retain-seq, identifies thousands of CpG-rich promoter-like human elements that tether episomes to mitotic chromosomes, shape ecDNA structure, and lose function when methylated.

Cis-Regulatory Element and Transcription Factor Circuitry Required for Cell-Type Specific Expression of FOXP3

The paper identifies cis-regulatory elements and transcription factors controlling FOXP3 expression in human Tregs and Tconvs, revealing mechanisms that restrict FOXP3 to Tregs in mice.

Enhancer activation from transposable elements in extrachromosomal DNA

The paper identifies enhancer-like elements on ecDNA in colorectal cancer that are derived from transposable elements and are functionally active in cancer cell fitness.

PLI Analyzer for Data-driven Validation of AI Predicted Biomolecular Interfaces

PLI-Analyzer evaluates AI-predicted biomolecular interfaces by analyzing atomic contacts and domain annotations, revealing discrepancies in predicted protein-protein complexes.

Local translation of circular RNAs is required for synaptic activity and memory

The paper identifies local translation of circular RNAs in the prefrontal cortex of mice, revealing a micropeptide involved in synaptic activity and memory.

Extrachromosomal DNA driven oncogene spatial heterogeneity and evolution in glioblastoma

This study investigates the spatial-temporal evolution of extrachromosomal DNA (ecDNA) in glioblastoma, showing that EGFR ecDNA drives tumor evolution and identifies a potential therapeutic window for early intervention.

Accurate Prediction of ecDNA in Interphase Cancer Cells using Deep Neural Networks

The paper introduces interSeg, a deep learning tool that accurately predicts oncogene amplification status from interphase FISH images, achieving high accuracy in detecting ecDNA and chromosomal amplifications.

Induced B-Cell Receptor Diversity Predicts PD-1 Blockade Immunotherapy Response.

This study identifies induced B-cell receptor diversity as a predictor of PD-1 blockade immunotherapy response across multiple cancer types.

Extrachromosomal DNA micronucleation constrains tumour fitness andimproves patient survival

This study shows that ecDNA mis-segregation leads to micronuclei formation, reduced oncogene transcription, and improved patient survival in neuroblastoma.

EcDNA-borne PVT1 fusion stabilizes oncogenic mRNAs

The paper shows that ecDNA-borne PVT1 fusions stabilize oncogenic mRNAs by interacting with SRSF1, enhancing RNA stability and supporting MYC dependency in cancer.

Single-cell multiome and enhancer connectome of human retinal pigment epithelium and choroid nominate pathogenic variants in age-related macular degeneration

The paper creates a single-cell multiome atlas of RPE and choroid tissues to identify pathogenic variants and mechanisms in AMD using HiChIP, Activity-by-Contact, and STARR-seq.

Autoantibody hotspots reveal origin and impact of immunogenic XIST ribonucleoprotein complex

The paper identifies autoantibody hotspots on the XIST RNP complex in female-biased autoimmune diseases and links them to clinical outcomes.

Rampant transcription replication conflict creates therapeutic vulnerability in extrachromosomal DNA containing cancers

This paper identifies transcription-replication conflict as a vulnerability in ecDNA-containing cancers and demonstrates that CHK1 inhibition selectively kills these tumors.

A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis

This study identifies a STAG2-PAXIP1/PAGR1 tumor-suppressive axis in lung cancer by showing their combined role in suppressing oncogenic KRAS-driven tumorigenesis.

Spatial organization of the 3D genome encodes gene co-expression programs in single cells

The paper investigates how 3D genome organization, specifically through Cohesin, influences gene co-expression in single cells and reveals its role in maintaining long-range chromatin interactions.

Bidirectional epigenetic editing reveals hierarchies in gene regulation

This study introduces CRISPRai, a bidirectional epigenetic editing system, to investigate gene regulation hierarchies and interactions in T cells and hematopoietic lineage transcription factors.

ProteinCLIP: enhancing protein language models with natural language

ProteinCLIP refines pre-trained protein language model embeddings using contrastive learning between amino acid sequences and functional text, achieving state-of-the-art results in protein tasks.

Epigenetic signature and key transcriptional regulators of human antigen-specific type 1 regulatory T cells

This study identifies the epigenetic signature and key transcription factors regulating human antigen-specific Tr1 cells, revealing their unique biology and potential for therapeutic applications.

Escape from X inactivation is directly modulated by levels of Xist non-coding RNA

This study shows Xist RNA modulates X-chromosome inactivation beyond early development, reversibly silencing escapee genes and altering topological domain structures in mouse embryos.