A5063223059- Connective tissue disorders research
- Tendon Structure and Treatment
- Skin and Cellular Biology Research
- S100 Proteins and Annexins
- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- Bone and Dental Protein Studies
- Reproductive Biology and Fertility
- RNA Research and Splicing
- Knee injuries and reconstruction techniques
- Osteoarthritis Treatment and Mechanisms
- Lung Cancer Treatments and Mutations
- TGF-β signaling in diseases
- Ion channel regulation and function
- Oral Health Pathology and Treatment
- Bone health and treatments
- Lysosomal Storage Disorders Research
- Cancer, Stress, Anesthesia, and Immune Response
- Microtubule and mitosis dynamics
- Salivary Gland Disorders and Functions
- Glycogen Storage Diseases and Myoclonus
- Hair Growth and Disorders
- Gynecological conditions and treatments
- Brain Metastases and Treatment
- Wnt/β-catenin signaling in development and cancer
The University of Texas MD Anderson Cancer Center
2022-2024
Baylor College of Medicine
2017-2024
Institute of Biomedical Sciences, Academia Sinica
2010-2019
National Defense Medical Center
2014-2016
Tri-Service General Hospital
2016
Duke Medical Center
2016
Institute of Biomedical Science
2016
Academia Sinica
2016
China Medical University
2016
Sungkyunkwan University
2007
The Taiwan Biobank (TWB) aims to build a nationwide research database that integrates genomic/epigenomic profiles, lifestyle patterns, dietary habits, environmental exposure history and long-term health outcomes of 300,000 residents Taiwan. We describe here an investigation the population structure Han Chinese on this Pacific island using genotype data 591,048 SNPs in initial freeze 10,801 unrelated TWB participants. In addition North-South cline reported other populations, we find Taiwanese...
The aim of this study was to evaluate, for the first time, differences in gene expression profiles normal and osteoarthritic (OA) subchondral bone human subjects. Following histological assessment integrity overlying cartilage severity abnormality by micro-computed tomography, we isolated total RNA from regions interest OA (n = 20) non-OA 5) knee lateral tibial (LT) medial (MT) plateaus. A whole-genome profiling performed on an Agilent microarray platform analyzed using GeneSpring GX11.5....
BACKGROUNDCurrently, there is no disease-specific therapy for osteogenesis imperfecta (OI). Preclinical studies demonstrate that excessive TGF-β signaling a pathogenic mechanism in OI. Here, we evaluated children with OI and conducted phase I clinical trial of inhibition adults OI.METHODSHistology RNA-Seq were performed on bones obtained from children. Gene Ontology (GO) enrichment assay, gene set analysis (GSEA), Ingenuity Pathway Analysis (IPA) used to identify dysregulated pathways....
Advances in molecular technologies and targeted therapeutics have accelerated the implementation of precision oncology, resulting improved clinical outcomes selected patients. The use next-generation sequencing assessments immune other biomarkers helps optimize patient treatment selection. In this review, oncology trials including IMPACT, SHIVA, IMPACT2, NCI-MPACT, TAPUR, DRUP, NCI-MATCH studies are summarized, their challenges opportunities discussed. Brief summaries new ComboMATCH,...
Palmitoyltransferase (PAT) catalyses protein S-palmitoylation which adds 16-carbon palmitate to specific cysteines and contributes various biological functions. We previously reported that in mice, deficiency of Zdhhc13, a member the PAT family, causes severe phenotypes including amyloidosis, alopecia, osteoporosis. Here, we show Zdhhc13 results abnormal liver function, lipid abnormalities, hypermetabolism. To elucidate molecular mechanisms underlying these disease phenotypes, applied...
Protein palmitoylation has emerged as an important mechanism for regulating protein trafficking, stability, and protein–protein interactions; however, its relevance to disease processes is not clear. Using a genome-wide, phenotype driven N-ethyl-N-nitrosourea–mediated mutagenesis screen, we identified mice with failure thrive, shortened life span, skin hair abnormalities including alopecia, severe osteoporosis, systemic amyloidosis (both AA AL amyloids depositions). Whole-genome homozygosity...
Abstract Achondroplasia (ACH), the most common genetic dwarfism in human, is caused by a gain-of function mutation fibroblast growth factor receptor 3 ( FGFR3 ). Currently, there no effective treatment for ACH. The development of an appropriate human-relevant model important testing potential therapeutic interventions before human clinical trials. Here, we have generated ACH mouse which endogenous Fgfr3 gene was replaced with G380R ) cDNA, Heterozygous ACH/+ and homozygous ACH/ACH mice...
Osteoarthritis (OA) is a degenerative disease of synovial joints characterized by progressive loss articular cartilage, subchondral bone remodeling, and intra-articular inflammation with synovitis that results in chronic pain motor impairment. Despite the economic health impacts, current medical therapies are targeted at symptomatic relief OA fail to alter its progression. Given complexity pathogenesis, we hypothesized combinatorial gene therapy approach, designed inhibit interleukin-1...
ZDHHC13 is a member of DHHC-containing palmitoyl acyltransferases (PATs) family enzymes. It functions by post-translationally adding 16-carbon palmitate to proteins through thioester linkage. We have previously shown that mice carrying recessive Zdhhc13 nonsense mutation causing Zdhcc13 deficiency develop alopecia, amyloidosis and osteoporosis. Our goal was investigate the pathogenic mechanism osteoporosis in context this mice. Body size, skeletal structure trabecular bone were similar WT...
Pathogenic variants in genes encoding components of the BRG1-associated factor (BAF) chromatin remodeling complex have been associated with intellectual disability syndromes. We identified heterozygous, novel ACTL6A, a gene component BAF complex, three subjects varying degrees disability. Two missense affecting highly conserved amino acid residues within actin-like domain. Missense mutations homologous region yeast actin were previously reported to be dominant lethal and impaired binding...
Tendons transmit contractile forces between musculoskeletal tissues. Whereas the biomechanical properties of tendons have been studied extensively, molecular mechanisms regulating postnatal tendon development are not well understood. Here we examine role mTORC1 signaling in using mouse genetic approaches. Loss by removal Raptor caused severe defects postnatally, including decreased thickness, indicating that is necessary for development. By contrast, activation increased cell numbers and...
Kinesin motor proteins transport intracellular cargo, including mRNA, proteins, and organelles. Pathogenic variants in kinesin-related genes have been implicated neurodevelopmental disorders skeletal dysplasias. We identified de novo, heterozygous KIF5B, encoding a kinesin-1 subunit, four individuals with osteogenesis imperfecta. The cluster within the highly conserved kinesin domain are predicted to interfere nucleotide binding, although mechanistic consequences on cell signaling function unknown.
Osteogenesis imperfecta (OI) type V is the second most common form of OI, distinguished by hyperplastic callus formation and calcification interosseous membranes in addition to bone fragility. It caused a recurrent, dominant pathogenic variant (c.-14C>T) IFITM5. Here, we generated conditional Rosa26 knock-in mouse model study mechanistic consequences recurrent mutation. Expression mutant Ifitm5 osteo-chondroprogenitor or chondrogenic cells resulted low mass growth retardation. Mutant limbs...
To identify susceptibility genes to nonfamilial hypokalemic periodic paralysis (hypoKPP) consisting of thyrotoxic (TPP) and sporadic (SPP) explore the potential pathogenic mechanisms.We enrolled patients with hypoKPP not carrying mutations in CACNA1S, SCN4A, KCNJ18, or KCNJ2 conducted genome-wide association analyses comparing 77 TPP 32 SPP 1,730 controls a Han Chinese population Taiwan. Replication was performed using an independent cohort 50 TPP, 22 SPP, 376 controls.We identified 4 single...
We investigated the challenges of conducting IMPACT2, an ongoing randomized study that evaluates molecular testing and targeted therapy (ClinicalTrials.gov: NCT02152254). Patients with metastatic cancer underwent tumor profiling were between two arms when eligibility criteria met (Part A). In Part B, patients who declined randomization could choose arm. A, 69 (21.8%) 317 randomized; 78.2% not because non-targetable alterations (39.8%), unavailability clinical trial (21.8%), other reasons...
Type V collagen is a regulatory fibrillar essential for type I fibril nucleation and organization its deficiency leads to structurally abnormal extracellular matrix (ECM). Haploinsufficiency of the Col5a1 gene encoding α(1) chain primary cause classic Ehlers-Danlos syndrome (EDS). The mechanisms by which this initial insult spectrum clinical presentation are not fully understood. Using transcriptome analysis skin Achilles tendons from haploinsufficient (Col5a1+/-) mice, we recognized...
Glioblastoma, the most common malignant brain tumor in adults, is associated with a median overall survival duration of less than 2 years. Extraneural metastases occur 1% all patients glioblastoma. The mechanism extraneural metastasis unclear. We present case extensive extraneural, extraosseous, epidural, and soft-tissue diagnosis metastatic glioblastoma was made only after next-generation sequencing (NGS) paraspinal lesions completed. CDK4, pTERT, PTEN, TP53 molecular alterations seen...