A5083510148- Hippo pathway signaling and YAP/TAZ
- Hedgehog Signaling Pathway Studies
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Wnt/β-catenin signaling in development and cancer
- Ubiquitin and proteasome pathways
- Gut microbiota and health
- Click Chemistry and Applications
- Pluripotent Stem Cells Research
- Pancreatic function and diabetes
- Plant Surface Properties and Treatments
- Lipid metabolism and biosynthesis
- Intensive Care Unit Cognitive Disorders
- Chemical Synthesis and Analysis
- Anesthesia and Neurotoxicity Research
- Peptidase Inhibition and Analysis
- Wound Healing and Treatments
- Genetic and rare skin diseases.
- Inflammasome and immune disorders
- Complement system in diseases
- Microtubule and mitosis dynamics
- Metabolism, Diabetes, and Cancer
- Sarcoma Diagnosis and Treatment
- Fibroblast Growth Factor Research
- Cell Adhesion Molecules Research
Massachusetts General Hospital
2016-2025
Harvard University
2016-2025
Capital Medical University
2019-2025
Southwest Medical University
2022-2025
Hunan Normal University
2022-2025
Hunan Provincial People's Hospital
2022-2025
Shanghai Cell Therapy Research Institute
2022-2025
First Affiliated Hospital of Sichuan Medical University
2022-2025
University of Louisiana at Lafayette
2024-2025
University of South China
2024
Wnt signaling is one of the key oncogenic pathways in multiple cancers, and targeting this pathway an attractive therapeutic approach. However, success has been limited because lack agents for targets a defined patient population that would be sensitive to inhibitor. We developed screen small molecules block secretion. This effort led discovery LGK974, potent specific small-molecule Porcupine (PORCN) PORCN membrane-bound O-acyltransferase required dedicated palmitoylation ligands, necessary...
Osteoarthritis (OA) is a degenerative joint disease that involves the destruction of articular cartilage and eventually leads to disability. Molecules promote selective differentiation multipotent mesenchymal stem cells (MSCs) into chondrocytes may stimulate repair damaged cartilage. Using an image-based high-throughput screen, we identified small molecule kartogenin, which promotes chondrocyte (median effective concentration = 100 nM), shows chondroprotective effects in vitro, efficacious...
Resistance of medulloblastoma to Smo antagonists can be delayed or prevented by specific drug combinations.
The blockade of aberrant hedgehog (Hh) signaling has shown promise for therapeutic intervention in cancer. A cell-based phenotypic high-throughput screen was performed, and the lead structure (1) identified as an inhibitor Hh pathway via antagonism Smoothened receptor (Smo). Structure-activity relationship studies led to discovery a potent specific antagonist N-(6-((2S,6R)-2,6-dimethylmorpholino)pyridin-3-yl)-2-methyl-4'-(trifluoromethoxy)biphenyl-3-carboxamide (5m, NVP-LDE225), which is...
Hippo signaling is a tumor-suppressor pathway involved in organ size control and tumorigenesis through the inhibition of YAP TAZ. Here, we show that energy stress induces cytoplasmic retention S127 phosphorylation inhibits transcriptional activity YAP-dependent transformation. These effects require central metabolic sensor AMP-activated protein kinase (AMPK) upstream components Lats1/Lats2 angiomotin-like 1 (AMOTL1). Furthermore, AMPK directly phosphorylates S793 AMOTL1. activation...
Macrophages undergoing M1- versus M2-type polarization differ significantly in their cell metabolism and cellular functions. Here, global quantitative time-course proteomics phosphoproteomics paired with transcriptomics provide a comprehensive characterization of temporal changes metabolism, functions, signaling pathways that occur during the induction phase polarization. Significant differences in, especially, metabolic are observed, including glucose glycosaminoglycan retinoic acid...
Abstract Targeting TEAD autopalmitoylation has been proposed as a therapeutic approach for YAP-dependent cancers. Here we show that palmitoylation inhibitor MGH-CP1 and analogues block cancer cell “stemness”, organ overgrowth tumor initiation in vitro vivo. sensitivity correlates significantly with YAP-dependency large panel of lines. However, inhibition or YAP/TAZ knockdown leads to transient cycle progression without inducing death, undermining their potential utilities. We further reveal...
Combinatorial libraries were screened for molecules that induce mouse myogenic lineage committed cells to dedifferentiate in vitro. A 2,6-disubstituted purine, reversine, was discovered induces reversal of C2C12 become multipotent progenitor which can redifferentiate into osteoblasts and adipocytes. This other such are likely provide new insights the molecular mechanisms control cellular dedifferentiation may ultimately be useful vivo stem cell biology therapy.
A phenotypic cell-based screen of a large combinatorial chemical library led to the identification class diaminopyrimidine compounds (cardiogenol A−D) which can selectively and efficiently induce mouse embryonic stem cells (ESCs) differentiate into cardiomyocytes. ESC-derived cardiomyocytes were shown express multiple cardiac muscle markers, including myosin heavy chain, GATA-4, MEF2, Nkx2.5, spontaneously form beating regions. Such small molecules will serve as useful probes study...
Purmorphamine, which is a 2,6,9-trisubstituted purine compound, was discovered through cell-based high-throughput screening from heterocycle combinatorial library. It differentiates multipotent mesenchymal progenitor cells into an osteoblast lineage. will serve as unique chemical tool to study the molecular mechanisms of osteogenesis stem and bone development.
The common inhalation anesthetic isoflurane has been shown to induce apoptosis, which then leads accumulation of beta-amyloid protein, the hallmark feature Alzheimer disease neuropathogenesis. underlying molecular mechanism isoflurane-induced apoptosis is largely unknown. We, therefore, set out assess whether can by regulating Bcl-2 family proteins, enhancing reactive oxygen species (ROS) accumulation, and activating mitochondrial pathway apoptosis. We performed these studies in cultured...
Background Recent studies have suggested that children undergoing surgery under anesthesia could be at an increased risk for the development of learning disabilities, but whether anesthetics contribute to this disability is unclear. Therefore, authors set out assess effects sevoflurane, most commonly used inhalation anesthetic, on caspase activation, apoptosis, beta-amyloid protein levels, and neuroinflammation in brain tissues neonatal naïve Alzheimer disease (AD) transgenic mice. Methods...
Significance Embryonal rhabdomyosarcoma (ERMS) is a cancer of skeletal muscle and one the most common pediatric cancers soft tissue. There no effective treatment for patients with relapsed ERMS, less than 50% surviving disease. The self-renewing molecularly defined tumor propagating cells (TPCs) drive continued growth relapse. Yet to date, drugs targeting ERMS self-renewal differentiation TPCs have not been identified. Our study describes large-scale chemical screen identify targetable...