A5037297279- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Peptidase Inhibition and Analysis
- Nonlinear Optical Materials Research
- Fibroblast Growth Factor Research
- RNA Research and Splicing
- Transgenic Plants and Applications
- Renal and related cancers
- Connective tissue disorders research
- Cancer Cells and Metastasis
- Supramolecular Self-Assembly in Materials
- Plant and Biological Electrophysiology Studies
- Cytokine Signaling Pathways and Interactions
- Bone health and osteoporosis research
- Neurobiology and Insect Physiology Research
- Bone Metabolism and Diseases
- Congenital heart defects research
- CAR-T cell therapy research
- Yersinia bacterium, plague, ectoparasites research
- Developmental Biology and Gene Regulation
- Toxin Mechanisms and Immunotoxins
- Bacterial Genetics and Biotechnology
- Neurological diseases and metabolism
- Soft tissue tumor case studies
- Fluorine in Organic Chemistry
Princess Máxima Center
2020-2025
Stanford University
2012-2023
Howard Hughes Medical Institute
2012-2022
MRC Laboratory of Molecular Biology
2010
Wnts are lipid-modified morphogens that play critical roles in development principally through engagement of Frizzled receptors. The 3.25 angstrom structure Xenopus Wnt8 (XWnt8) complex with mouse Frizzled-8 (Fz8) cysteine-rich domain (CRD) reveals an unusual two-domain Wnt structure, not obviously related to known protein folds, resembling a "hand" "thumb" and "index" fingers extended grasp the Fz8-CRD at two distinct binding sites. One site is dominated by palmitoleic acid lipid group...
Frizzleds (Fzd) are the primary receptors for Wnt morphogens, which essential regulators of stem cell biology, yet structural basis signaling through Fzd remains poorly understood. Here we report structure an unliganded human Fzd5 determined by single-particle cryo-EM at 3.7 Å resolution, with aid antibody chaperone acting as a fiducial marker. We also analyzed topology low-resolution XWnt8/Fzd5 complex particles, revealed extreme flexibility between Wnt/Fzd-CRD and Fzd-TM regions. Analysis...
Wnt morphogens are critical for embryonic development and tissue regeneration. Canonical Wnts form ternary receptor complexes composed of tissue-specific Frizzled (Fzd) receptors together with the shared LRP5/6 coreceptors to initiate β-catenin signaling. The cryo-EM structure a initiation complex an affinity-matured XWnt8–Frizzled8–LRP6 elucidates basis coreceptor discrimination by canonical means their N termini linker domains that engage LRP6 E1E2 domain funnels. Chimeric bearing modular...
Abstract Glucocorticoids, such as dexamethasone, are essential for treating severe childhood conditions, including cancer, organ transplantation, and inflammatory disorders. However, their long-term use can impair bone development, posing risks to pediatric health, which is vital lifelong skeletal integrity. A mechanistic insight on how glucocorticoids negatively impact could improve decision-making in patient care the quality of life cancer patients survivors. In this study, we aimed...
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 tumor patient-matched normal kidney organoids to identify potential CAR T targets. Integrating these findings transcriptomics protein expression data, revealed ROBO1 as a promising target, showing strong uniform across other tumors. ROBO1-targeted cells displayed potent...
Abstract The Wnt signaling pathway is intricately connected with bone mass regulation in humans and rodent models. We designed an antibody-based platform that generates potent selective mimetics. Using this platform, we engineer bi-specific mimetics target Frizzled low-density lipoprotein receptor-related proteins evaluate their effects on accrual murine These synthetic agonists induce rapid robust building effects, correct deficiency defects various disease models, including osteoporosis,...
<title>Abstract</title> 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 tumor patient-matched normal kidney organoids to identify potential CAR T targets. Integrating these findings transcriptomics protein expression data, revealed ROBO1 as a promising target, showing strong uniform across other tumors. ROBO1-targeted...
Matrigel ® /BME , a basement membrane-like preparation, supports long-term growth of epithelial 3D organoids from adult stem cells [T. Sato et al. Nature 459 262–265 (2009); T. Gastroenterology 141 1762–1772 (2011)]. Here, we show that interaction between Matrigel’s major component laminin-111 with α6β1-integrin is crucial for this process. The outer membrane protein Invasin Yersinia known to activate multiple integrin–β1 complexes, including integrin α6β1. A C-terminal integrin-binding...
Abstract 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 β-catenin signaling. The structure a complex an affinity-matured XWnt8-Frizzled8-LRP6 elucidates basis co-receptor discrimination by canonical means their N-termini linker domains that engage LRP6 E1E2 domain funnels. Chimeric bearing modular ‘grafts’ were...