Biology subjects

Kuo, Y.-C.

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

5 recordsLinked to original sources

bioRxiv2026

Meditope-Enabled Chimeric Antigen Receptors Facilitate Plug-and-Play Control of T Cells

Chimeric antigen receptor (CAR) T cells have transformed cancer treatment, yet challenges for achieving broader clinical success remain, including overcoming tumor antigen heterogeneity and limited T cell fitness. To address these challenges and enhance CAR T cell functionality, we leveraged meditope technology, a lock-and-key platform where Fab regions of antibodies are modified to bind a small cyclic peptide termed meditope (meP). We developed a panel of meditope-enabled Fab-based CARs (meCARs), which show selective binding to the meP and comparable activity to traditional single-chain variable fragment (scFv)-based CARs. Focusing on HER2-targeted meCARs for evaluating platform utility, we exploited the modularity of the meditope platform to detect meCAR T cells using meP-fused fluorescent agents, promote meCAR T cell expansion via meP-fused IL-15 cytokine, and broaden tumor antigen targeting through meP-fused antibodies to address tumor heterogeneity. These findings establish the meditope technology as a versatile strategy to augment CAR T cell functionality and overcome key limitations of current CAR-based therapies.

bioengineering↗

bioRxiv2026

Latent-centric Isotropic Resolution Enhancement for Expansion Microscopy Imaging via Neural Compression and Self-supervised Learning

Expansion microscopy (ExM) enables nanoscale imaging for disease characterization. However, whole-organ analyses remain limited by several challenges. Current super-resolution methods either require high-resolution ground-truth data or assume spatially uniform point spread functions--assumptions that rarely hold in whole-organ imaging with depth-varying aberrations and illumination drift. Existing methods also worsen storage demands by inflating already multi-terabyte datasets without using neural compression. We propose a single-stage, self-supervised framework that addresses both resolution anisotropy and storage constraints through compression-aware isotropic super-resolution. Our approach combines a 2D lateral encoder that operates directly on raw slices to avoid memory limits with a lightweight volumetric decoder that preserves cross-slice continuity. A vector-quantized variational autoencoder (VQ-VAE) provides an information-sufficient bottleneck, achieving up to 128x slice compression and up to 8x axial resolution enhancement. This latent-centric design yields approximately 1000x reduction in storage compared with storing fully isotropic volumes. The framework achieves higher GPU throughput, lower memory usage, and stronger multi-GPU scalability than prior methods. By designating compressed latent space as the native storage format, it enables efficient on-demand isotropic reconstruction directly from compact representations. This combination of isotropic enhancement and neural compression framework therefore makes large-scale, whole-organ ExM analysis practical while maintaining analysis-ready accessibility, addressing a bottleneck in translating ExM to clinical biomarker discovery.

bioinformatics↗

bioRxiv2020

The structural mechanism underlying the antithetic effect of homologous RND1 and RhoD GTPases in plexin regulation

Plexins are semaphorin receptors that play essential roles in neuronal axon guidance and in many other important biological processes. Plexin signaling depends on a semaphorin-induced dimerization mechanism, and is modulated by small signaling GTPases of the Rho family, of which RND1 serves as a plexin activator yet its close homolog RhoD an inhibitor. Using molecular dynamics (MD) simulations we showed that RND1 reinforces plexin dimerization interface whereas RhoD destabilizes it due to their differential interaction with cell membrane. Upon binding plexin dimers at the Rho-GTPase binding (RBD) domains, RND1 and RhoD interact differently with the inner leaflet of cell membrane, and exert opposite effects on the dimerization interface via an allosteric network involving the RBD domain, RBD linkers, and a buttress segment adjacent to the dimerization interface. The differential membrane interaction is attributed to the fact that, unlike RND1, RhoD features a short C-terminal tail and a positively-charged membrane interface.

biophysics↗

bioRxiv2020

Mapping the Antibody Repertoires in Ferrets with Repeated Influenza A/H3 Infections: Is Original Antigenic Sin Really "Sinful"?

The influenza-specific antibody repertoire is continuously reshaped by infection and vaccination. The host immune response to contemporary viruses can be redirected to preferentially boost antibodies specific for viruses encountered early in life, a phenomenon called original antigenic sin (OAS) that is suggested to be responsible for diminished vaccine effectiveness after repeated vaccination. In this study, we used a new computational tool called Neutralization Map to determine the hemagglutination inhibition profiles of individual antibodies within ferret antisera elicited by repeated influenza A/H3 infections. Our results suggest that repeated infections continuously reshape the ferret antibody repertoire, but that a broadly neutralizing antibody signature can nevertheless be induced irrespective of OAS. Overall, our study offers a new way to visualize how immune history shapes individual antibodies within a repertoire, which may help inform future vaccine design.

immunology↗

bioRxiv2017

Combined Androgen Administration and HDAC Inhibition in Experimental Cancer Cachexia

PurposeThe common colon-26 mouse (C-26) model of experimental cachexia mimics recent late stage clinical failures of anabolic anti-cachexia therapy, and does not respond to the anabolic selective androgen receptor modulator (SARM) GTx-024. Based on the demonstrated anti-cachectic efficacy of the histone deacetylase inhibitor (HDACi) AR-42 in this model, we hypothesized that combined SARM/AR-42 would provide improved anti-cachectic efficacy.\n\nDesignIn the C-26 model, we determined a reduced efficacious dose of AR-42 which was combined with anabolic SARM therapy and evaluated for anti-cachectic efficacy. The effects of treatment and tumor burden on anabolic and catabolic signaling occurring in skeletal muscle were characterized using muscle performance parameters and RNA-seq.\n\nResultsAnabolic anti-cachexia therapy with diverse androgens had no impact on cachectic outcomes in the C-26 model. A reduced dose of the HDACi AR-42 alone provided limited anti-cachectic benefits, but when combined with the SARM GTx-024, significantly improved bodyweight (p<0.0001), hind limb muscle mass (p<0.05), and voluntary grip strength (p<0.0001) versus tumor-bearing controls. Reduced-dose AR-42 treatment suppressed the IL-6/GP130/STAT3 signaling axis without significantly impacting circulating cytokine levels. GTx-024-mediated {beta}-catenin target gene regulation was apparent in cachectic mice only when combined with AR-42.\n\nConclusionsCachectic signaling in the C-26 model is comprised of catabolic signaling insensitive to anabolic GTx-024 therapy and a blockade of GTx-024-mediated anabolic signaling. AR-42 treatment mitigates catabolic gene activation and restores anabolic responsiveness to GTx-024. Combining GTx-024, a clinically established anabolic therapy, with a low dose of AR-42, a clinically evaluated HDACi, represents a promising approach to improve anabolic response in cachectic patient populations.

cancer biology↗