Biology subjects

Huang, T. Y.

Publications and source records attributed to Huang, T. Y..

3 recordsLinked to original sources

bioRxiv2025

StrucTrace: Fourier Watermarking for Traceable Bio-molecular Assets

The rise of generative artificial intelligence (GenAI) in protein and nucleic acid design has created unprecedented opportunities for synthetic biology, but also heightened the need for reliable provenance and intellectual-property protection. To meet this challenge, we present a Fourier domain watermarking framework that encodes digital identifiers directly into three-dimensional biomolecular structures. By perturbing only flexible backbone atoms and embedding information through frequency domain modulation, the method achieves imperceptible alterations while ensuring deterministic and reversible decoding. Large-scale validation on over 40,000 protein structures demonstrates its robustness: structural deviations remain orders of magnitude below biological thresholds, watermarks are recovered with perfect accuracy, and functional analyses confirm stability at both thermodynamic and dynamic levels. Beyond technical performance, the approach provides a foundation for a broader ecosystem of secure biomolecular asset management, integrating provenance verification, access control, and digital rights management. Together, these advances establish biomolecules as traceable and auditable digital assets, aligning the future of bio-design with emerging standards for trustworthy AI.

bioinformatics↗

bioRxiv2025

SORLA upregulation suppresses global pathological effects in aged tauopathy mouse brain

A role for the trafficking receptor SORLA in reducing A{beta} levels has been well-established, however, relatively little is known with respect to whether and how SORLA can potentially affect tau pathology in vivo. Here, we show that transgenic SORLA upregulation (SORLA TG) can reverse pathological effects in aged PS19 (P301S tau) mouse brain, including tau phosphorylation and seeding, ventricle dilation, synapse loss, LTP impairment and glial hyperactivation. Proteomic analysis indicates reversion of PS19 profiles in PS19/SORLA TG hippocampus, including pathological changes in synapse-related proteins as well as key drivers of synaptic dysfunction such as Apoe and C1q. snRNA-seq analysis reveals suppression of PS19- signatures with SORLA upregulation, including proinflammatory induction of Plxnb1/Plxnb2 in glia. Tau seeding and aggregation, neuroinflammation, as well as PlxnB1/B2 induction are exacerbated in PS19 hippocampus with SORLA deletion. These results implicate a global role for SORLA in neuroprotection from tau toxicity in PS19 mouse brain.

neuroscience↗

bioRxiv2024

SUV39H1 Preserves Cancer Stem Cell Chromatin State and Properties in Glioblastoma

Of the more than 100 types of brain cancer, glioblastoma (GBM) is the deadliest. As GBM stem cells (GSCs) are considered to be responsible for therapeutic resistance and tumor recurrence, effective targeting and elimination of GSCs could hold promise for preventing GBM recurrence and achieving potential cures. We show here that SUV39H1, which encodes a histone-3, lysine-9 methyltransferase, plays a critical role in GSC maintenance and GBM progression. Upregulation of SUV39H1 was observed in GBM samples compared to normal brain tissues, and knockdown of SUV39H1 in patient-derived GSCs impaired their proliferation and stemness. Single-cell RNA-seq analysis demonstrated restricted expression of SUV39H1 is in GSCs relative to non-stem GBM cells, likely due to super-enhancer-mediated transcriptional activation, while whole cell RNA-seq analysis revealed that SUV39H1 regulates G2/M cell cycle progression, stem cell maintenance, and cell death pathways in GSCs. By integrating the RNA-seq data with ATAC-seq (assay for transposase-accessible chromatin followed by sequencing), we further demonstrated altered chromatin accessibility in key genes associated with these pathways following SUV39H1 knockdown. Treatment with chaetocin, a SUV39H1 inhibitor, mimicked the functional effects of SUV39H1 knockdown in GSCs and sensitized GSCs to the GBM chemotherapy drug temozolomide. Furthermore, targeting SUV39H1 in vivo using a patient-derived xenograft model for GBM inhibited GSC-driven tumor formation. This is the first report demonstrating a critical role for SUV39H1 in GSC maintenance. SUV39H1-mediated targeting of GSCs could enhance the efficacy of existing chemotherapy, presenting a promising strategy for improving GBM treatment and patient outcomes. HighlightsO_LISUV39H1 is upregulated in GBM, especially GSCs C_LIO_LITargeting SUV39H1 disrupts GSC maintenance and sensitizes GSCs to TMZ C_LIO_LITargeting SUV39H1 alters chromatin accessibility at cell cycle and stemness genes C_LIO_LITargeting SUV39H1 suppresses GSC-driven tumors in a patient-derived xenograft model C_LI

cancer biology↗