A5027262882- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Developmental Biology and Gene Regulation
- Skin and Cellular Biology Research
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Genomics and Chromatin Dynamics
- Psoriasis: Treatment and Pathogenesis
- HER2/EGFR in Cancer Research
- Molecular Biology Techniques and Applications
- Dermatology and Skin Diseases
- Pancreatic and Hepatic Oncology Research
- Genetic factors in colorectal cancer
- Cancer-related Molecular Pathways
- RNA Research and Splicing
- Monoclonal and Polyclonal Antibodies Research
- Hippo pathway signaling and YAP/TAZ
- Cardiac Arrhythmias and Treatments
- AI in cancer detection
- Epigenetics and DNA Methylation
- Cell Image Analysis Techniques
- Digital Imaging for Blood Diseases
- Single-cell and spatial transcriptomics
- Cardiac electrophysiology and arrhythmias
- Fibroblast Growth Factor Research
Roche (United States)
2024
Novartis (United States)
2014-2024
Huntington University
2021
Leidos (United States)
2020
Novartis (Switzerland)
2015-2019
Novartis Institutes for BioMedical Research
2019
Biogen (United States)
2011-2016
The University of Texas Southwestern Medical Center
2003-2012
Southwestern Medical Center
2006-2009
Howard Hughes Medical Institute
2000-2002
BackgroundHyperactivity of the IL-23/IL-17 axis is central to plaque psoriasis pathogenesis. Secukinumab, a fully human mAb that selectively inhibits IL-17A, approved for treatment psoriasis, psoriatic arthritis, and ankylosing spondylitis. Secukinumab improves complete spectrum manifestations, with durable clinical responses beyond 5 years treatment. In feed-forward model chronicity, IL-17A has been hypothesized as key driver pathogenic gene expression by lesional keratinocytes, but in vivo...
Context.— The adoption of digital capture pathology slides as whole slide images (WSI) for educational and research applications has proven utility. Objective.— To compare pathologists' primary diagnoses derived from WSI versus the standard microscope. Because WSIs differ in format method observation compared with current glass microscopy, this study is critical to potential clinical pathology. Design.— enrolled a total 2045 cases enriched more difficult diagnostic categories represented...
In Drosophila embryos the protein Naked cuticle (Nkd) limits effects of Wnt signal Wingless (Wg) during early segmentation. nkd loss function results in segment polarity defects and embryonic death, but how affects signaling is unknown. Using ectopic expression, we find that Nkd affects, a cell-autonomous manner, transduction step between components Dishevelled (Dsh) Zeste-white 3 kinase (Zw3). Zw3 essential for repressing Wg target-gene transcription absence signal, role to relieve this...
Abstract Hepatoblastomas are the most frequent malignant liver tumors of childhood. A high frequency activating β-catenin mutations in hepatoblastomas indicates that Wnt signaling pathway plays an important role development this embryonic neoplasm. Stabilization leads to increased formation nuclear β-catenin-T-cell factor complexes and altered expression Wnt-inducible target genes. In study, we analyzed mRNA levels nine genes, including c-JUN, c-MYC, CYCLIN D1, FRA-1, NKD-1, ITF-2, MMP-7,...
A morphology-based assay such as immunohistochemistry (IHC) should be a highly effective means to define the expression of target molecule interest, especially if is protein. However, over past decade, IHC platform for biomarkers has been challenged by more quantitative molecular assays with reference standards but that lack morphologic context. For considered “top-tier” biomarker assay, it must provide truly data on par non-morphologic assays, which needs run standards. creating will...
Osteoarthritis (OA) is a common, debilitating, chronic disease with no disease-modifying drug approved to date. We discovered LNA043-a derivative of angiopoietin-like 3 (ANGPTL3)-as potent chondrogenesis inducer using phenotypic screen human mesenchymal stem cells. show that LNA043 promotes and cartilage matrix synthesis in vitro regenerates hyaline articular preclinical OA injury models vivo. exerts at least part these effects through binding the fibronectin receptor, integrin α5β1 on cells...
ABSTRACT Central nervous system midline cells constitute a discrete group of Drosophila embryonic with numerous functional and developmental roles. Corresponding to their separate identity, the display patterns gene expression distinct from lateral central system. A conserved 5 base pair sequence (ACGTG) was identified in transcriptional enhancers three genes. Germ-line transformation experiments indicate that this motif forms core an element required for transcription. The is related...
Certain untoward effects associated with the use of direct‐current electrical catheter ablation ventricular endomyocardium have been noted. We assessed efficacy and safety closed‐chest left right ventricles using radio frequency (RF) energy (750 kHz) in six dogs. Mean HF energies between 93 123 joules (J) were randomly delivered to three (LV) sites via two distal adjacent electrodes (bipolar configuration) 6–7F USCI tripolar or quadripolar catheters an interelectrode distance 5–10 mm....
Mesothelioma is an aggressive malignancy with heterogeneous outcomes that are partly driven by the differential efficacy of existing therapies across histologic types and sites origin. Large-scale molecular analysis mesothelioma its subtypes has potential to inform future therapeutic strategies.We analyzed 1,294 mesotheliomas {980 pleural (malignant [MPM]) 314 peritoneal [MPeM])} using next-generation sequencing, determined programmed death ligand-1 (PD-L1) expression histology in a subset...
Mutation of Wnt signal antagonists Apc or Axin activates beta-catenin signaling in many cancers including the majority human colorectal adenocarcinomas. The phenotype apc axin mutation fruit fly Drosophila melanogaster is strikingly similar to that caused by segment-polarity gene, naked cuticle (nkd). Nkd inhibits binding Dishevelled (Dsh/Dvl) family scaffold proteins link receptor activation accumulation and TCF-dependent transcription, but NKD genes have yet be directly implicated...
Epithelial tubes are the functional units of many organs, and proper tube geometry is crucial for organ function. Here, we characterize serrano (sano), a novel cytoplasmic protein that apically enriched in several tube-forming epithelia Drosophila, including tracheal system. Loss sano results elongated tracheae, whereas Sano overexpression causes shortened tracheae with reduced apical boundaries. during larval pupal stages planar cell polarity (PCP) defects adult tissues. In...
Gradients of Wnt/β-catenin signaling coordinate development and physiological homeostasis in metazoan animals. Proper embryonic the fruit fly Drosophila melanogaster requires Naked cuticle (Nkd) protein to attenuate a gradient across each segmental anlage. Nkd inhibits Wnt by binding intracellular Dishevelled (Dsh). Mice humans have two nkd homologs, nkd1 nkd2, whose encoded proteins can bind Dsh homologs (the Dvl proteins) inhibit signaling. To determine whether genes are necessary for...
Over half of adults are seropositive for JC polyomavirus (JCV), but rare individuals develop progressive multifocal leukoencephalopathy (PML), a demyelinating JCV infection the central nervous system. Previously, PML was primarily seen in immunosuppressed patients with AIDS or certain cancers, it has recently emerged as drug safety issue through its association diverse immunomodulatory therapies. To better understand relationship between life cycle and pathology, we studied autopsy brain...
During Drosophila development, thenaked cuticle (nkd) gene attenuates wingless/Wnt signaling through a negative feedback loop mechanism. Fly and vertebrate Nkd proteins contain putative calcium-binding EF-hand motif, the EFX domain, that interacts with basic/PDZ region of Wnt signal transducer, dishevelled (Dsh). Here we show Dsh binding by in vitro is mediated domain as well an adjacent C-terminal sequence. In vivo data suggest both these regions contribute to ability antagonize signaling....
Abstract Wnt/β-catenin signals orchestrate cell fate and behavior throughout the animal kingdom. Aberrant Wnt signaling impacts nearly entire spectrum of human disease, including birth defects, cancer, osteoporosis. If is to be effectively manipulated for therapeutic advantage, we first must understand how are normally controlled. Naked cuticle (Nkd) a novel evolutionarily conserved inducible antagonist that crucial segmentation in model genetic organism, fruit fly Drosophila melanogaster....