A5069272338- Zebrafish Biomedical Research Applications
- Cellular Mechanics and Interactions
- Bone health and osteoporosis research
- RNA Research and Splicing
- Bone Metabolism and Diseases
- Congenital heart defects research
- Morphological variations and asymmetry
- Single-cell and spatial transcriptomics
- Connective tissue disorders research
- Molecular Biology Techniques and Applications
- Neurogenetic and Muscular Disorders Research
- Genetics, Bioinformatics, and Biomedical Research
- Developmental Biology and Gene Regulation
- Bone fractures and treatments
- Genetic and Kidney Cyst Diseases
- MicroRNA in disease regulation
- RNA modifications and cancer
- Bone health and treatments
- Muscle Physiology and Disorders
- Bone and Joint Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Cell Image Analysis Techniques
- Fish Biology and Ecology Studies
- Genetic Syndromes and Imprinting
- Genetics and Physical Performance
University of Washington
2016-2025
Seattle University
2017-2023
California Institute for Regenerative Medicine
2020
La Jolla Bioengineering Institute
2010-2012
University of California, Berkeley
2012
Stanford University
2006-2010
Veterans Health Administration
2008-2009
VA Palo Alto Health Care System
2009
Palo Alto Veterans Institute for Research
2007
Primary cilia are sensory organelles that translate extracellular chemical and mechanical cues into cellular responses. Bone is an exquisitely mechanosensitive organ, its homeostasis depends on the ability of bone cells to sense respond stimuli. One such stimulus dynamic fluid flow, which triggers biochemical transcriptional changes in by unknown mechanism. Here we report possess primary project from cell surface deflect during flow these required for osteogenic resorptive responses flow. We...
Many biochemical factors regulating progenitor cell differentiation have been examined in detail; however, the role of local mechanical environment on stem fate has only recently investigated. In this study, we whether oscillatory fluid flow, an exogenous signal within bone, regulates osteogenic, adipogenic or chondrogenic C3H10T1/2 murine mesenchymal cells by measuring Runx2, PPARgamma and SOX9 gene expression, respectively. Furthermore, hypothesized that small GTPase RhoA isometric tension...
Abstract Microglia, the innate immune cells of brain, influence Alzheimer’s disease (AD) progression and are potential therapeutic targets. However, microglia exhibit diverse functions, regulation which is not fully understood, complicating therapeutics development. To better define transcriptomic phenotypes gene regulatory networks associated with AD, we enriched for nuclei from 12 AD 10 control human dorsolateral prefrontal cortices (7 males 15 females, all aged >60 years) before...
Primary cilia are chemosensing and mechanosensing organelles that regulate remarkably diverse processes in a variety of cells. We previously showed primary play role mediating bone cells through an unknown mechanism does not involve extracellular Ca(2+)-dependent intracellular Ca(2+) release, which has been implicated all other transduce mechanical signals via the cilium. Here, we identify molecular linking cell mechanotransduction involves adenylyl cyclase 6 (AC6) cAMP. Intracellular cAMP...
The type I collagenopathies are a group of heterogeneous connective tissue disorders, that caused by mutations in the genes encoding collagen and include specific forms osteogenesis imperfecta (OI) Ehlers-Danlos syndrome (EDS). These disorders present with broad disease spectrum large clinical variability which underlying genetic basis is still poorly understood. In this study, we systematically analyzed skeletal phenotypes set zebrafish, diverse collagen, representing different human OI,...
ABSTRACT Bruck syndrome (BS) is a disorder characterized by joint flexion contractures and skeletal dysplasia that shows strong clinical overlap with the brittle bone disease osteogenesis imperfecta (OI). BS caused biallelic mutations in either FKBP10 or PLOD2 gene. encodes lysyl hydroxylase 2 (LH2) enzyme, which responsible for hydroxylation of lysine residues fibrillar collagen telopeptides. This directs crosslinking fibrils extracellular matrix, necessary to provide stability tensile...
Phenomics, which ideally involves in-depth phenotyping at the whole-organism scale, may enhance our functional understanding of genetic variation. Here, we demonstrate methods to profile hundreds phenotypic measures comprised morphological and densitometric traits a large number sites within axial skeleton adult zebrafish. We show potential for vertebral patterns confer heightened sensitivity, with similar specificity, in discriminating mutant populations compared analyzing individual...
Interstitial fluid flow (IFF) has been widely hypothesized to mediate skeletal adaptation mechanical loading. Although a large body of in vitro evidence demonstrated that stimulates osteogenic and antiresorptive responses bone cells, there is much less vivo IFF mediates loading-induced adaptation. This due part the challenges associated with decoupling from matrix strain. In this study we describe novel microfluidic system for generating dynamic intramedullary pressure (ImP) within femurs...
The generation and sensation of mechanical force plays a role in many dynamic biological processes, including touch sensation. This paper presents two-axis micro strain gauge sensor constructed from multiple layers SU-8 metal on quartz substrates. was designed to meet requirements for measuring tactile sensitivity interaction forces exerted during locomotion by small organisms such as the nematode Caenorhabditis elegans. device is transparent compatible with light microscopes, allowing...
Zebrafish regenerate fin rays following amputation through epimorphic regeneration, a process that has been proposed to involve the epithelial-to-mesenchymal transition (EMT). We performed single-cell RNA sequencing (scRNA-seq) elucidate osteoblastic transcriptional programs during zebrafish caudal regeneration. show osteoprogenitors are enriched with components associated EMT and its reverse, mesenchymal-to-epithelial (MET), provide evidence markers cdh11 twist2 co-expressed in...
Heritable Fragile Bone Disorders (FBDs) encompass a spectrum of conditions, from widespread multifactorial to rare monogenic diseases, all characterized by an elevated risk fractures. The process validating causative genes and elucidating their pathogenic mechanisms remains daunting resource-intensive task. In this study, we evaluated the feasibility semi-high throughput zebrafish screening platform for rapid validation in vivo functional testing candidate disease-causing wide range...
Heritable fragile bone disorders (FBDs), ranging from multifactorial to rare monogenic conditions, are characterized by an elevated fracture risk. Validating causative genes and understanding their mechanisms remain challenging. We assessed a semi-high throughput zebrafish screening platform for rapid in vivo functional testing of candidate FBD genes. Six linked severe recessive osteogenesis imperfecta (OI) four associated with mineral density (BMD) genome-wide association studies were...
ABSTRACT Intramuscular administration of Botulinum toxin (BTx) has been associated with impaired osteogenesis in diverse conditions bone formation (eg, development, growth, and healing), yet the mechanisms neuromuscular-bone crosstalk underlying these deficits have to be identified. Motivated by emerging utility zebrafish (Danio rerio) as a rapid, genetically tractable, optically transparent model for human pathologies (as well potential interrogate neuromuscular-mediated disorders simple...
Interstitial fluid flow (IFF) is a potent regulatory signal in bone. During mechanical loading, IFF generated through two distinct mechanisms that result spatially profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While former generates primarily network, latter significant at endosteal surface as well tissue. This gives rise to intriguing possibility loading-induced may differentially activate osteocytes or surface-residing cells...