Biology subjects

Janda, C. Y.

Publications and source records attributed to Janda, C. Y..

3 recordsLinked to original sources

bioRxiv2026

A Dual-Pathway Wnt-IL-13 Fusion Protein Enhances Human Intestinal Regeneration Through Tuft Cell Activation

Compromised intestinal regenerative responses drive severe inflammatory conditions, such as inflammatory bowel disease and graft-versus-host disease, affecting millions of people worldwide each year. Despite extensive research, effective therapies remain limited, and no curative treatments are currently available. We recently discovered that human intestinal tuft cells promote tissue repair following injury through Wnt and IL-4/IL-13 signaling pathways. Building on this discovery, here we report the engineering and functional validation of a synthetic Wnt-IL-13 fusion protein that simultaneously activates both the Wnt and IL-4/IL-13 signaling pathways to enhance human intestinal tuft cell activity. Employing human organoids technology, we demonstrate that this therapeutic approach promotes mucosal healing.

biochemistry↗

bioRxiv2025

Cell surface proteomics of patient-derived malignant rhabdoid tumor organoids identifies ROBO1 as potential CAR T cell target for pediatric solid tumors.

Malignant rhabdoid tumors are highly aggressive pediatric malignancies with limited treatment options and poor outcomes. To expand therapeutic options, we employed mass spectrometry-based cell surface proteomics on malignant rhabdoid tumor and patient-matched normal kidney organoids to identify potential CAR T cell targets. Integrating these findings with transcriptomics and protein expression data, we revealed ROBO1 as a promising target, showing strong and uniform expression across malignant rhabdoid and other pediatric tumors. ROBO1-targeted CAR T cells displayed potent anti-tumor activity in vitro, effectively eliminating tumor cells in co-cultures with organoids from malignant rhabdoid tumors, rhabdomyosarcoma, and neuroblastoma. In vivo, ROBO1 CAR T cells infiltrated tumors, induced potent tumor regression and significantly increased survival in malignant rhabdoid tumor-bearing mice. These findings establish ROBO1 as a compelling therapeutic target for CAR T cell therapy and offer a promising approach to address the critical need for effective treatments in high-risk pediatric solid tumors. Statement of significanceThis study identifies ROBO1 as a promising CAR T cell target for pediatric solid tumors. Using patient-derived tumor organoids and tissues, we demonstrate strong ROBO1 expression across several tumor entities and robust anti-tumor efficacy of ROBO1-targeted CAR T cells in vitro and in vivo, underscoring its potential for clinical translation.

cancer biology↗

bioRxiv2022

Structure of the Wnt-Frizzled-LRP6 initiation complex reveals the basis for co-receptor discrimination

Wnt morphogens are critical for embryonic development and tissue regeneration. Canonical Wnts form ternary receptor complexes composed of tissue-specific Frizzled receptors together with the shared LRP5/6 co-receptors to initiate {beta}-catenin signaling. The structure of a ternary complex of an affinity-matured XWnt8-Frizzled8-LRP6 complex elucidates the basis of co-receptor discrimination by canonical Wnts by means of their N-termini and linker domains that engage the LRP6 E1E2 domain funnels. Chimeric Wnts bearing modular linker grafts were able to transfer LRP6 domain specificity between different Wnts and enable non-canonical Wnt5a to signal through the canonical pathway. Synthetic peptides comprising the linker domain serve as Wnt-specific antagonists. The structure of the ternary complex provides a topological blueprint for the orientation and proximity of Frizzled and LRP6 within the Wnt cell surface signalosome.

biophysics↗