Biology subjects

Cheong, S.

Publications and source records attributed to Cheong, S..

5 recordsLinked to original sources

bioRxiv2026

Thrombospondin-2 deficiency primes the synovial joint for aberrant tissue remodeling and injury response

ObjectiveThis study investigates joint injury-induced angiogenesis and the effects of genetic deficiency of thrombospondin-2 (TSP2), an anti-angiogenic factor, in joint homeostasis and post-traumatic osteoarthritis (PTOA). MethodWe utilized a murine non-invasive anterior cruciate ligament rupture (ACLR) model of PTOA and mined published synovial transcriptomics datasets to investigate injury-induced synovial angiogenesis. Spatial transcriptomics and flow cytometry of TSP2-GFP reporter mice were used to assess injury-induced thrombospondin-2 and its cellular origins in synovium. Global TSP2 knockout mice (TSP2-KO) were used to assess the effect of TSP2 deficiency on early and late stages of PTOA development via molecular imaging of inflammation and angiogenesis, histopathology, micro-computed tomography, Raman spectroscopy, and synovium bulk RNA-sequencing. ResultsIntra-articular angiogenesis peaked at 7d post-ACLR and declined but remained elevated above baseline at 28d post-ACLR. We identified synovial crosstalk between endothelial cells and sublining fibroblasts as a key driver of angiogenesis and source of thrombospondin-2 signaling, with TSP2 primarily upregulated in sublining fibroblasts. TSP2-KO mice exhibited increased peri-articular inflammation at 7d post-ACLR and inferior bone quality. Histopathology revealed greater PTOA severity but paradoxically lower synovitis in TSP2-KOs. Additionally, aberrant structural remodeling of the entire knee joint was observed in uninjured and ACLR TSP2-KO limbs. The uninjured TSP2-KO synovial transcriptome demonstrated elevated immune, fibrotic, and angiogenic activation; however, TSP2-KO and WT synovial transcriptomes partially converged upon injury. ConclusionTSP2 is essential for joint homeostasis and trauma response. Global TSP2 deficiency causes premature OA and worsened PTOA, suggesting that therapeutic targeting with TSP2 mimetic could be used to prevent OA.

physiology↗

bioRxiv2026

A network-based deep learning model integrating subclonal architecture for therapy response prediction in cancer

Predicting treatment response remains challenging in oncology, particularly given the growing diversity of therapeutic options. Despite efforts using gene expression signatures, or integrative multi-omics frameworks, robust and interpretable biomarkers remain limited. We present SubNetDL, a deep learning framework that integrates subclonal mutation profiles and protein-protein interaction networks via network propagation. Unlike condition-specific approaches, SubNetDL leverages somatic mutations alone and is applicable across diverse cancer types and treatment modalities. Applied to ten TCGA cancer-drug combinations, SubNetDL achieved consistently strong performance (median AUROC = 0.74) and successfully generalized to two independent immunotherapy datasets (median AUROC = 0.77). Importantly, it identified candidate biomarker genes with treatment-specific relevance. SubNetDL prioritized genes that were not central in the network, highlighting its ability to capture context-specific patterns beyond traditional metrics. In conclusion, our approach offers a robust and interpretable framework for identifying predictive biomarkers and stratifying patients based on mutation profiles and network context. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/711567v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@d31c74org.highwire.dtl.DTLVardef@1f12b13org.highwire.dtl.DTLVardef@430916org.highwire.dtl.DTLVardef@109a13c_HPS_FORMAT_FIGEXP M_FIG C_FIG MotivationIntratumoral heterogeneity is a fundamental driver of therapeutic resistance, yet most predictive models rely on aggregate mutational burdens or static gene expression signatures, overlooking the subclonal dynamics that shape treatment outcomes. While network biology offers a functional lens to interpret genomic alterations, a framework that explicitly bridges subclonal architecture with system-level molecular interactions has been lacking. To address this, we developed SubNetDL, a deep learning framework that integrates patient-specific subclonal profiles with protein-protein interaction networks. By leveraging only somatic mutation data, SubNetDL captures the functional convergence of subclonal evolution, providing a robust and interpretable platform for patient stratification and biomarker discovery across diverse oncological contexts.

cancer biology↗

bioRxiv2024

A polyketide-based biosynthetic platform for diols, amino alcohols and hydroxyacids

Medium- and branched-chain diols and amino alcohols are important industrial solvents, polymer building blocks, cosmetics and pharmaceutical ingredients, yet biosynthetically challenging to produce. Here, we present a novel approach utilising a modular polyketide synthase (PKS) platform for the efficient production of these compounds. This platform takes advantage of a versatile loading module from the rimocidin PKS and NADPH-dependent terminal thioreductases (TRs), previously untapped in engineered PKSs. Reduction of the terminal aldehyde with specific alcohol dehydrogenases enables production of diols, oxidation enables production of hydroxy acids, and transamination with specific transaminases enables production of various amino alcohols. Furthermore, replacement of the malonyl-coenzyme A (CoA)-specific acyltransferase (AT) in the extension module with methyl- or ethylmalonyl- CoA-specific ATs enables production of branched-chain diols and amino alcohols. In total, we demonstrated production of nine 1,3-diols (including the difficult-to-produce insect repellent and cosmetic ingredient 2-ethyl-1,3-hexanediol), six amino alcohols, and two carboxylic acids using our PKS platform in Streptomyces albus. Finally, tuning production of the PKS acyl-CoA substrates enabled production of high titers of specific diols and amino alcohols (1 g/L diol titer in shake flasks), demonstrating high tunability and efficiency of the platform.

bioengineering↗

bioRxiv2022

A highly active Burkholderia polyketoacyl-CoA thiolase for production of triacetic acid lactone

Triacetic acid lactone (TAL) is a platform chemical biosynthesized primarily through decarboxylative Claisen condensation by type III polyketide synthase 2-pyrone synthase (2-PS). However, this reaction suffers from intrinsic energy inefficiency and feedback inhibition by and competition for malonyl-CoA. TAL production through non-decarboxylative Claisen condensation by polyketoacyl-CoA thiolase alleviates many of these disadvantages. We discovered five more thiolases with TAL production activity by exploring homologs of a previously reported polyketoacyl-CoA thiolase, BktB, from Cupriavidus necator. Among them, the BktB homolog from Burkholderia sp. RF2-non_BP3 has [~] 30 times higher in vitro and in vivo TAL production activity and led to [~]10 times higher TAL titer than 2-PS when expressed in Escherichia coli, achieving a titer of 2.8 g/L in fed-batch fermentations. This discovery of a novel polyketoacyl-CoA thiolase with superior TAL production activity paves the way for realization of total biomanufacturing of TAL.

bioengineering↗

bioRxiv2021

Training with an auditory perceptual learning game transfers to speech in competition

Hearing speech in competition is a major complaint in those who suffer from hearing loss. Here we investigate a novel perceptual learning game that is designed to train perceptual skills thought to underlie speech in competition, such as spectral-temporal processing and sound localization, under conditions of quiet and in noise. Thirty young normal hearing participants were assigned either to this mixed-training condition or an active control consisting of frequency discrimination training within the same gamified setting. To assess training outcomes, we examine tests of basic central auditory processing, speech in competition, and cognitive processing abilities before and after training. Results suggest modest improvements on speech in competition tests in the mixed-training but not the frequency-discrimination control condition. This data show promise for future applications in populations with hearing difficulties.

animal behavior and cognition↗