Biology subjects

Tung, Y.-C.

Publications and source records attributed to Tung, Y.-C..

3 recordsLinked to original sources

bioRxiv2026

Robust volumetric multiplex staining of centimeter-scale FFPE tissues guided by neural network-based optimization

Archived formalin-fixed, paraffin-embedded (FFPE) tissues, including brain-bank specimens, are valuable resources for disease research, but rapid cyclic immunolabeling of intact specimens remains challenging. Here, we present FIDELITY, an epoxy-free workflow that balances optical transparency, immunostaining performance, and tissue integrity for multi-cycle protein profiling in centimeter-thick FFPE specimens. Neural network-guided optimization identified an SDS-glycine formulation that integrates delipidation and epitope retrieval while preserving tissue stiffness, replacing prolonged epoxy reinforcement and subsequent high-temperature antigen retrieval with a single aqueous pretreatment. Application to human Alzheimer's disease specimens enabled volumetric imaging and quantitative analysis while retaining compatibility with conventional histopathology. Its compatibility with active electrophoretic staining further supported rapid labeling and five rounds of immunolabeling in a whole FFPE mouse brain. Two-round labeling of a human glioma specimen further demonstrated the applicability of the cyclic workflow to human pathological tissue. Together, FIDELITY provides a practical platform for large-volume, multiplexed protein profiling of intact FFPE specimens.

neuroscience↗

bioRxiv2025

Cuticular collagens mediate cross-kingdom predator-prey interactions between nematodes and trapping fungi

Adhesive interactions, mediated by specific molecular and structural mechanisms, are fundamental to host-pathogen and predator-prey relationships, driving evolutionary dynamics and ecological interactions. Here, we investigate the cellular and molecular basis of adhesion between the nematode Caenorhabditis elegans and its natural predator the nematode-trapping fungus Arthrobotrys oligospora, which employs specialized adhesive nets to capture its prey. Using forward genetic screens, we identified C. elegans mutants that escape fungal traps and revealed the nuclear hormone receptor NHR-66 as a key regulator of fungal-nematode adhesion. Loss-of-function mutations in nhr-66 conferred resistance to fungal trapping through the downregulation of a large subset of cuticular collagen genes. Restoring collagen gene expression in nhr-66 mutants abolished the escape phenotype, highlighting the essential role of these structural proteins in fungal-nematode adhesion. Furthermore, sequence analysis of natural C. elegans populations revealed no obvious loss-of-function variants in nhr-66, suggesting selective pressures exist that balance adhesion-mediated predation risk with physiological robustness. We observed that loss of nhr-66 function resulted in a trade-off of increased hypersensitivity to hypoosmotic stress and cuticular fragility. These findings underscore the pivotal role of structural proteins in shaping ecological interactions and the evolutionary arms race between predator and prey.

evolutionary biology↗

bioRxiv2022

ECM-derived biophysical cues mediate interstitial flow-induced sprouting angiogenesis

Sprouting angiogenesis is orchestrated by an intricate balance of biochemical and mechanical cues in the local microenvironment. Interstitial flow has been established as a potent regulator of angiogenesis. Similarly, extracellular matrix (ECM) physical properties, such as stiffness and microarchitecture, have also emerged as important mediators of angiogenesis. Yet, the interplay between interstitial flow and ECM physical properties in the initiation and control of angiogenesis is poorly understood. Using a 3-D microfluidic tissue analogue of angiogenic sprouting with defined interstitial flow, we found that the addition of hyaluronan (HA) to collagen-based matrices significantly enhances sprouting induced by interstitial flow compared to responses in collagen-only hydrogels. We confirmed that both the stiffness and matrix pore size of collagen-only hydrogels were increased by the addition of HA. Interestingly, interstitial flow-potentiated sprouting responses in collagen/HA matrices were not affected when functionally blocking the HA receptor CD44. In contrast, enzymatic depletion of HA in collagen/HA matrices with hyaluronidase (HAdase) resulted in decreased stiffness, pore size, and interstitial flow-mediated sprouting to the levels observed in collagen-only matrices. Taken together, these results suggest that HA enhances interstitial flow-mediated angiogenic sprouting through its alterations to collagen ECM stiffness and pore size.

bioengineering↗