Biology subjects

Tian, W.

Publications and source records attributed to Tian, W..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

CTHRC1 is a new therapeutic target and serum diagnostic biomarker for aortic dissection

Aortic dissection (AD) is a cardiovascular disease with rapid onset and extremely high short-term mortality, currently lacking specific peripheral blood-based biomarkers and effective treatments. Here, our analysis of AD samples from animal models and human patients revealed elevated blood levels of CTHRC1, a protein secreted by vascular fibroblasts. Furthermore, CTHRC1 regulates the phenotypic switch of vascular smooth muscle cells (VSMCs) during arterial remodeling by binding to ADAM9 on the VSMC membrane, activating the ERK1/2 signaling pathway, and promoting a contractile-to-synthetic transition. In Ang-II/BAPN induced mouse models, genetic ablation or antibody-mediated blockade of CTHRC1 effectively prevented AD development. These findings unveil CTHRC1 as a critical regulator of VSMC phenotype and aortic structural integrity via the ERK1/2 pathway, suggesting its potential as a novel serum diagnostic biomarker for AD diagnostic and a promising therapeutic target. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/649636v1_ufig1.gif" ALT="Figure 1"> View larger version (75K): org.highwire.dtl.DTLVardef@6a3f14org.highwire.dtl.DTLVardef@15353e7org.highwire.dtl.DTLVardef@1a9928forg.highwire.dtl.DTLVardef@1d4ef3d_HPS_FORMAT_FIGEXP M_FIG C_FIG In briefCTHRC1 is aberrantly expressed in aortic adventitial fibroblasts from dissected aortas and function as an exocrine mediator that induces phenotypic switching of vascular smooth muscle cells. A monoclonal antibody targeting CTHRC1 demonstrates therapeutic potential in mouse models of aortic dissection. HighlightsO_LICTHRC1 is highly expressed in aortic adventitial fibroblasts from dissected aortas C_LIO_LICTHRC1 interacts with ADAM9 to induce phenotypic switching of VSMCs C_LIO_LIAn anti-CTHRC1 antibody inhibits aortic dissection formationinvivo C_LIO_LIElevated levels of serum CTHRC1 can be used to identify AD in patients presenting with chest pain C_LI

cell biology↗

bioRxiv2025

Cell-type-specific transposable element demethylation and TAD remodeling in the aging mouse brain

Aging is a major risk factor for neurodegenerative diseases, yet underlying epigenetic mechanisms remain unclear. Here, we generated a comprehensive single-nucleus cell atlas of brain aging across multiple brain regions, comprising 132,551 single-cell methylomes and 72,666 joint chromatin conformation-methylome nuclei. Integration with companion transcriptomic and chromatin accessibility data yielded a cross-modality taxonomy of 36 major cell types. We observed that age-related methylation changes were more pronounced in non-neuronal cells. Transposable element methylation alone distinguished age groups, showing cell-type-specific genome-wide demethylation. Chromatin conformation analysis demonstrated age-related increases in TAD boundary strength with enhanced accessibility at CTCF binding sites. Spatial transcriptomics across 895,296 cells revealed regional heterogeneity during aging within identical cell types. Finally, we developed novel deep-learning models that accurately predict age-related gene expression changes using multi-modal epigenetic features, providing mechanistic insights into gene regulation. This dataset advances our understanding of brain aging and offers potential translational applications. HighlightsO_LISingle-cell multi-omic profiling maps the epigenetic and spatial transcriptomic landscape of brain aging across multiple regions. C_LIO_LICell-type-specific genome-wide demethylation of retrotransposable elements correlates with increased chromatin accessibility and expression. C_LIO_LIElevated TAD boundary strength emerges as a unique marker of brain aging associated with CTCF gaining accessibility. C_LIO_LIA novel deep-learning model reveals the significance of epigenetic features on age-related transcriptomic changes across genes. C_LI

genomics↗

bioRxiv2025

Discovery of D2469079A, A novel selective Toll-Like Receptor 7/8 Antagonist with Brain Penetrance

Aberrant activation of endosomal Toll-like receptors (TLRs) 7 and 8, which recognize single-stranded RNA, is strongly implicated in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). And the frequent neuropsychiatric involvement in SLE highlights the need for brain-penetrant therapies. Here, we report the identification and characterization of D2469079A, a novel, potent dual TLR7/TLR8 antagonist (low nM IC50 in humanized HEK-Blue assays) selective against hTLR9. D2469079A demonstrates favorable in vitro properties, including adequate solubility and high microsomal stability. It exhibited desirable pharmacokinetic profiles across multiple preclinical species (mice, rats, dogs) and achieved significant cerebrospinal fluid (CSF) exposure, confirming its high permeability and brain penetration. Consistent in vivo efficacy was observed in both acute and chronic stimulation models. Importantly, D2469079A displayed a favorable safety profile, lacking significant liabilities related to CYP450 inhibition/induction, hERG interaction, or toxicity in a 14-day rat study. These findings position D2469079A as a promising drug candidate with excellent drug-like characteristics for the treatment of TLR7/8-driven autoimmune diseases, potentially including neuropsychiatric manifestations. We are actively seeking partners for collaborative clinical development.

immunology↗

bioRxiv2025

Human Body Single-Cell Atlas of 3D Genome Organization and DNA Methylation

Higher-order chromatin structure and DNA methylation are critical for gene regulation, but how these vary across the human body remains unclear. We performed multi-omic profiling of 3D genome structure and DNA methylation for 86,689 single nuclei across 16 human tissues, identifying 35 major and 206 cell subtypes. We revealed extensive changes in CG and non-CG methylation across almost all cell types and characterized 3D chromatin structure at an unprecedented cellular resolution. Intriguingly, extensive discrepancies exist between cell types delineated by DNA methylation and genome structure, indicating that the role of distinct epigenomic features in maintaining cell identity may vary by lineage. This study expands our understanding of the diversity of DNA methylation and chromatin structure and offers an extensive reference for exploring gene regulation in human health and disease.

genomics↗

bioRxiv2025

A method for inducing a senescence trend in mesenchymal stem cells using D-galactose

The aging of the body is accompanied by a decline in tissue function, and this decline mainly stems from the aging of tissue stem cells. Therefore, they play a crucial role in the aging of the body.This study explores the biological characteristics of senescent hUCMSCs by establishing a replicative senescence model of hUCMSCs and a rapid senescence model induced by D - galactose (D-Gal), and analyzing the proliferative capacity, cell viability, cell cycle, pluripotency, and reactive oxygen species (ROS) levels of senescent hUCMSCs.

cell biology↗

bioRxiv2025

Multi-omics analysis of keratinocytes reveals dermokine-dependent regulation of cell-cell adhesion via p120

Loss of keratinocyte differentiation is a leading cause in several skin diseases and needs to be controlled in adult homeostasis by for instance growth factors and proteases. Among them, we studied the role of isoform-rich dermokine - a wound- and tumour-related matrix metalloproteinase 10 substrate - via functional multi-omics. We generated dermokine isoform-dependent keratinocyte knockouts and three dimensional (3D) organotypic skin cultures and analyzed changes in their proteome and phosphoproteome by quantitative mass spectrometry. Through functional in vitro assays, we demonstrate that in the absence of dermokine-isoforms, p120 phosphorylation increases while cell-cell adhesion decreases in keratinocytes. Furthermore, we validate the link between decreased dermokine expression and phosphorylated p120-mediated adhesion in non-healing wounds samples derived from patients. Our data reveal a novel dermokine-p120-dependent cell-cell adhesion phenotype in keratinocytes and improve our understanding of wound-edge keratinocytes, expanding the hypothesis that dysregulated wounds resemble cancer.

cell biology↗

bioRxiv2024

Marine medaka responds differently to dioxin compared with its close freshwater relative, the Japanese medaka: the AHR molecular mechanism

The global water pollution now calls for precise risk assessment of chemicals, e.g., dioxins and the emerging dioxin-like compounds (DLCs). The freshwater and marine medaka have been widely implemented in the toxicity testing, and perhaps give mechanistic information for comparative biology. The question that will they report equal results due to their close phylogenetic relation has been raised, therefore, we explored their physiological and molecular responses to dioxin. As the mediator of the dioxin toxicity, the aryl hydrocarbon receptor (AHR) of marine medaka (Oryzias melastigma) has not been functionally characterized and might be species-specific. In terms of sensitivity to dioxin--2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the EC50 values of omeAHR1a (0.16{+/-}0.12 nM), omeAHR1b (2.96{+/-}2.96 nM), omeAHR2a (0.44{+/-}0.30 nM), and omeAHR2b (9.00{+/-}6.88 nM) exhibit marked variations. The omeAHR2a and omeAHR1a display heightened sensitivity compared to the freshwater Japanese medaka (Oryzias latipes) counterparts olaAHR2a and olaAHR1a, respectively. The results indicate the in vitro sensitivity of AHR among species can vary by one or two orders of magnitude. Physiologically, the marine medaka (LC50: 1.64 ng/L (95% CI: 1.05-2.55 ng/L)) also exhibits a pronounced sensitivity to TCDD than Japanese medaka (LC50: 3.42 ng/L (95% CI: 1.37-6.48 ng/L), aligning with the in vitro AHR sensitivity. Further mechanistic investigations using additional ligands and computational modeling reveal that: 1) most of omeAHR2a, olaAHR2a, dreAHR2, and hsaAHR interact with ligands in the affinity order of TCDD > PCB126 > BNF > indole, mirroring their AHR transactivation potency, but the docking poses and dynamics can vary; 2) one AHR subforms high sensitivity to dioxin--TCDD may extend to DLCs but not to other types of ligands. These insights underscore the difference of AHR biology among species even the close relative species, and finger out the necessity for meticulous consideration when evaluating the toxicity of compounds and when extending predictive toxicity assessments to more species.

ecology↗

bioRxiv2024

TvAP65 in Trichomonas vaginalis Promotes HPV Infection by Interacting with Host Molecules

Cervical cancer induced by human papillomavirus (HPV) infection poses a serious threat to womens health. Studies have shown that Trichomonas vaginalis (T. vaginalis), which is widely prevalent globally, can facilitate HPV infection. However, the underlying mechanism remains unclear. This study found that T. vaginalis significantly enhanced HPV infection in HaCaT cells and mouse vaginas through in vivo and in vitro experiments, and promoted the expression of HPV membrane receptor molecules CD151 and HSPG2. The HPV infection rate and CD151/HSPG2 expression levels were significantly decreased after reducing the expression of T. vaginalis adhesion protein 65 (TvAP65). In contrast, both HPV infection rates and CD151/HSPG2 expression were significantly increased in HaCaT cells over-expressing TvAP65. When both TvAP65 in T. vaginalis and CD151/HSPG2 in HaCaT cells were knocked down simultaneously, the infection rate of HPV in HaCaT cells was further reduced. These results suggest that TvAP65 promotes HPV infection by up-regulating the expression of CD151 and HSPG2. Furthermore, this study knocked down the 12 interacting molecules of TvAP65 in HaCaT cells one by one, and found that the HPV infection rate was significantly reduced after T. vaginalis infected HaCaT cells with low expression of FTH1, SPCS1, ATP5MC3, ITGB7, PMEPA1 or REEP5. Among them, SPCS1 played the most significant role. Simultaneous knockdown of TvAP65 and SPCS1 further significantly down-regulated the infection rate of HPV in HaCaT cells. Moreover, this molecule also down-regulated the promoting effect of T. vaginalis on HSPG2/CD151 expression. These results imply that SPCS1 plays an important role in T. vaginalis promoting HSPG2/CD151 expression and HPV infection. This study not only further proved that T. vaginalis can promote HPV infection but also explores the molecular mechanism by which TvAP65, through its interaction with SPCS1, up-regulates the expression of HSPG2 and CD151, thereby facilitating HPV infection. This provides a theoretical basis for clarifying the mechanism of co-infection between T. vaginalis and HPV.

microbiology↗

bioRxiv2024

Comprehensive profiling of transcriptional regulation in cartilage reveals pathogenesis of osteoarthritis

Cartilage damage is a leading cause of osteoarthritis (OA) etiology, however, the underlying mechanism governing gene expression regulation in this progress is poorly understood. Here, we described a comprehensive profiling of transcriptional regulation of 235 primary human cartilage samples. We identified 3,352 independent significant expression quantitative trait loci (eQTLs) for 3,109 genes. We explored the candidate casual SNP and its underlying regulatory mechanism using our established functional fine-mapping pipeline by integrating the cartilage-specific ATAC-seq data. We identified 117 causal eQTLs that display allele-specific open chromatin (ASoC) and 547 transcription factor binding-disruption (TBD) eQTLs. We conducted cell type-interaction eQTL (ci-eQTL) analyses based on speculated chondrocyte subtype proportions and revealed the regulation relationship of 120 eQTL-gene pairs showed cell type dependency. Further, by integrating with genome-wide association studies (GWASs) data of OA, we nominated 43 candidate effector genes for OA risk loci. We verified that the T allele of the OA risk variant rs11750646 increased the AR binding affinity to an open chromatin region and promoted the expression of an OA-related gene PIK3R1. Altogether, our findings provide new insights into the unique regulatory landscape of cartilage and elucidate potential mechanisms underlying the OA pathogenesis.

genetics↗

bioRxiv2024

CASTpFold: Computed Atlas of Surface Topography of the universe of protein Folds

Geometric and topological properties of protein structures, including surface pockets, interior cavities, and cross channels, are of fundamental importance for proteins to carry out their functions. Computed Atlas of Surface Topography of proteins (CASTp) is a widely used web server for locating, delineating, and measuring these geometric and topological properties of protein structures. Recent developments in AI-based protein structure prediction such as AlphaFold2 (AF2) have significantly expanded our knowledge on protein structures. Here we present CASTpFold, a continuation of CASTp that provides accurate and comprehensive identifications and quantifications of protein topography. It now provides (i) results on an expanded database of proteins, including the Protein Data Bank (PDB) and non-singleton representative structures of AlphaFold2 structures, covering 183 million AF2 structures; (ii) functional pockets prediction with corresponding Gene Ontology (GO) terms or Enzyme Commission (EC) numbers for AF2-predicted structures; and (iii) pocket similarity search function for surface and protein-protein interface pockets. The CASTpFold web server is freely accessible at https://cfold.bme.uic.edu/castpfold/.

biophysics↗

bioRxiv2024

Global view of domain-specific O-linked mannose glycosylation in glycoengineered cells

Protein O-linked mannose (O-Man) glycosylation is an evolutionary conserved post-translational modification (PTM) that fulfills important biological roles during embryonic development. Three non-redundant enzyme families, POMT1/POMT2, TMTC1-4 and TMEM260, selectively coordinate the initiation of protein O-Man glycosylation on distinct classes of transmembrane proteins, including -dystroglycan, cadherins and plexin receptors. However, a systematic investigation of their substrate specificities is lacking, in part due to the ubiquitous expression of O-Man glycosyltransferases in cells, which precludes analysis of pathway-specific O-Man glycosylation on a proteome-wide scale. Here, we apply a targeted workflow for membrane glycoproteomics across five human cell lines to extensively map O-Man substrates and genetically deconstruct O-Man initiation by individual and combinatorial knock-out (KO) of O-Man glycosyltransferase genes. We established a human cell library for analysis of substrate specificities of individual O-Man initiation pathways by quantitative glycoproteomics. Our results identify 180 O-Man glycoproteins, demonstrate new protein targets for the POMT1/POMT2 pathway and show that TMTC1-4 and TMEM260 pathways widely target distinct Ig-like protein domains of plasma membrane proteins involved in cell-cell and cell-extracellular matrix interactions. The identification of O-Man on Ig-like folds adds further knowledge on the emerging concept of domain-specific O-Man glycosylation which opens for functional studies of O-Man glycosylated adhesion molecules and receptors.

molecular biology↗

bioRxiv2024

The PCM scaffold enables RNA localization to centrosomes

As microtubule-organizing centers, centrosomes direct assembly of the bipolar mitotic spindle required for chromosome segregation and genome stability. Centrosome activity requires the dynamic assembly of pericentriolar material (PCM), the composition and organization of which changes throughout the cell cycle. Recent studies highlight the conserved localization of several mRNAs encoded from centrosome-associated genes enriched at centrosomes, including Pericentrin-like protein (Plp) mRNA. However, relatively little is known about how RNAs localize to centrosomes and influence centrosome function. Here, we examine mechanisms underlying the subcellular localization of Plp mRNA. We find that Plp mRNA localization is puromycin-sensitive, and the Plp coding sequence is both necessary and sufficient for RNA localization, consistent with a co-translational transport mechanism. We identify regions within the Plp coding sequence that regulate Plp mRNA localization. Finally, we show that protein-protein interactions critical for elaboration of the PCM scaffold permit RNA localization to centrosomes. Taken together, these findings inform the mechanistic basis of Plp mRNA localization and lend insight into the oscillatory enrichment of RNA at centrosomes.

cell biology↗

bioRxiv2023

Epigenome erosion in Alzheimer's disease brain cells and induced neurons

Late-onset Alzheimers disease (LOAD) is typically sporadic, correlated only to advanced age, and has no clear genetic risk factors. The sporadic nature of LOAD presents a challenge to understanding its pathogenesis and mechanisms. Here, we comprehensively investigated the epigenome of LOAD primary entorhinal cortex brain tissues via single-cell multi-omics technologies, simultaneously capturing DNA methylation and 3D chromatin conformation. We identified AD-specific DNA methylation signatures and found they interact with bivalent promoters of AD differentially expressed genes. In addition, we discovered global chromosomal epigenome erosion of 3D genome structure within and across brain cell types. Furthermore, to evaluate whether these age- and disease-dependent molecular signatures could be detected in the in vitro cellular models, we derived induced neurons (iNs) converted directly from AD patients fibroblasts and found a set of conserved methylation signatures and shared molecular processes. We developed a machine-learning algorithm to identify robust and consistent methylation signatures of LOAD in vivo primary brain tissues and in vitro fibroblast-derived iNs. The results recapitulate the age- and disease-related epigenetic features in iNs and highlight the power of epigenome and chromatin conformation for identifying molecular mechanisms of neuronal aging and generating biomarkers for LOAD. HIGHLIGHTO_LIAD-specific DNA methylation signatures are identified in entorhinal cortex brain cell types C_LIO_LIThe AD differentially expressed genes linked with differentially methylated regions via loop interactions are enriched in a bivalent chromatin state C_LIO_LIChromosomal epigenome erosion of 3D genome structures occurs in LOAD brain cell types. C_LIO_LIShared and reliable methylation signatures are observed in both in vitro cellular iN models and primary brain tissues. C_LIO_LIMachine learning models identify robust and reliable methylation loci as AD biomarkers across cell types. C_LI

genomics↗

bioRxiv2023

BAllC and BAllCools: Efficient Formatting and Operating for Single-Cell DNA Methylation Data

MotivationWith single-cell DNA methylation studies yielding vast datasets, existing data formats struggle with the unique challenges of storage and efficient operations, highlighting a need for improved solutions. ResultsBAllC (Binary All Cytosines) emerges as a tailored binary format for methylation data, addressing these challenges. BAllCools, its complementary software toolkit, enhances parsing, indexing, and querying capabilities, promising superior operational speeds and reduced storage needs. Availabilityhttps://github.com/jksr/ballcools Contactecker@salk.edu Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2023

Human Immune Cell Epigenomic Signatures in Response to Infectious Diseases and Chemical Exposures

The epigenomic landscape of human immune cells is dynamically shaped by both genetic factors and environmental exposures. However, the relative contributions of these elements are still not fully understood. In this study, we employed single-nucleus methylation sequencing and ATAC-seq to systematically explore how pathogen and chemical exposures, along with genetic variation, influence the immune cell epigenome. We identified distinct exposure-associated differentially methylated regions (eDMRs) corresponding to each exposure, revealing how environmental factors remodel the methylome, alter immune cell states, and affect transcription factor binding. Furthermore, we observed a significant correlation between changes in DNA methylation and chromatin accessibility, underscoring the coordinated response of the epigenome. We also uncovered genotype-associated DMRs (gDMRs), demonstrating that while eDMRs are enriched in regulatory regions, gDMRs are preferentially located in gene body marks, suggesting that exposures and genetic factors exert differential regulatory control. Notably, disease-associated SNPs were frequently colocalized with meQTLs, providing new cell-type-specific insights into the genetic basis of disease. Our findings underscore the intricate interplay between genetic and environmental factors in sculpting the immune cell epigenome, offering a deeper understanding of how immune cell function is regulated in health and disease.

genomics↗

bioRxiv2023

Single-cell DNA Methylome and 3D Multi-omic Atlas of the Adult Mouse Brain

Cytosine DNA methylation is essential in brain development and has been implicated in various neurological disorders. A comprehensive understanding of DNA methylation diversity across the entire brain in the context of the brains 3D spatial organization is essential for building a complete molecular atlas of brain cell types and understanding their gene regulatory landscapes. To this end, we employed optimized single-nucleus methylome (snmC-seq3) and multi-omic (snm3C-seq1) sequencing technologies to generate 301,626 methylomes and 176,003 chromatin conformation/methylome joint profiles from 117 dissected regions throughout the adult mouse brain. Using iterative clustering and integrating with companion whole-brain transcriptome and chromatin accessibility datasets, we constructed a methylation-based cell type taxonomy that contains 4,673 cell groups and 261 cross-modality-annotated subclasses. We identified millions of differentially methylated regions (DMRs) across the genome, representing potential gene regulation elements. Notably, we observed spatial cytosine methylation patterns on both genes and regulatory elements in cell types within and across brain regions. Brain-wide multiplexed error-robust fluorescence in situ hybridization (MERFISH2) data validated the association of this spatial epigenetic diversity with transcription and allowed the mapping of the DNA methylation and topology information into anatomical structures more precisely than our dissections. Furthermore, multi-scale chromatin conformation diversities occur in important neuronal genes, highly associated with DNA methylation and transcription changes. Brain-wide cell type comparison allowed us to build a regulatory model for each gene, linking transcription factors, DMRs, chromatin contacts, and downstream genes to establish regulatory networks. Finally, intragenic DNA methylation and chromatin conformation patterns predicted alternative gene isoform expression observed in a companion whole-brain SMART-seq3 dataset. Our study establishes the first brain-wide, single-cell resolution DNA methylome and 3D multi-omic atlas, providing an unparalleled resource for comprehending the mouse brains cellular-spatial and regulatory genome diversity.

genomics↗

bioRxiv2023

Comparative single cell epigenomic analysis of gene regulatory programs in the rodent and primate neocortex

Sequence divergence of cis-regulatory elements drives species-specific traits, but how this manifests in the evolution of the neocortex at the molecular and cellular level remains to be elucidated. We investigated the gene regulatory programs in the primary motor cortex of human, macaque, marmoset, and mouse with single-cell multiomics assays, generating gene expression, chromatin accessibility, DNA methylome, and chromosomal conformation profiles from a total of over 180,000 cells. For each modality, we determined species-specific, divergent, and conserved gene expression and epigenetic features at multiple levels. We find that cell type-specific gene expression evolves more rapidly than broadly expressed genes and that epigenetic status at distal candidate cis-regulatory elements (cCREs) evolves faster than promoters. Strikingly, transposable elements (TEs) contribute to nearly 80% of the human-specific cCREs in cortical cells. Through machine learning, we develop sequence-based predictors of cCREs in different species and demonstrate that the genomic regulatory syntax is highly preserved from rodents to primates. Lastly, we show that epigenetic conservation combined with sequence similarity helps uncover functional cis-regulatory elements and enhances our ability to interpret genetic variants contributing to neurological disease and traits.

genomics↗

bioRxiv2023

A multidimensional atlas of human glioblastoma organoids reveals highly coordinated molecular networks and effective drugs

Recent advances in the genomics of glioblastoma (GBM) led to the introduction of molecular neuropathology but failed to translate into treatment improvement. This is largely attributed to the genetic and phenotypic heterogeneity of GBM, which are considered the major obstacle to GBM therapy. Here, we use advanced human GBM organoid (LEGO: Laboratory Engineered Glioblastoma Organoid) and provide an unprecedented comprehensive characterization of LEGO models using single-cell transcriptome, DNA methylome, metabolome, lipidome, proteome, and phospho-proteome analysis. We discovered that genetic heterogeneity dictates functional heterogeneity across molecular layers and demonstrates that NF1 mutation drives mesenchymal signature. Most importantly, we found that glycerol lipid reprogramming is a hallmark of GBM, and several targets and drugs were discovered along this line. We also provide a genotype-based drug reference map using LEGO-based drug screen. This study provides novel human GBM models and a research path toward effective GBM therapy.

cancer biology↗