A5072203009- Cardiac electrophysiology and arrhythmias
- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- Neuroscience and Neural Engineering
- Ion channel regulation and function
- Computational Drug Discovery Methods
- Congenital heart defects research
- SARS-CoV-2 and COVID-19 Research
- Adipose Tissue and Metabolism
- Immune Cell Function and Interaction
- Genetic Associations and Epidemiology
- Adipokines, Inflammation, and Metabolic Diseases
- Mitochondrial Function and Pathology
- Nuclear Receptors and Signaling
- Genetics and Physical Performance
- Transplantation: Methods and Outcomes
- Apelin-related biomedical research
- Hematopoietic Stem Cell Transplantation
- Respiratory viral infections research
- T-cell and B-cell Immunology
- Cardiac Ischemia and Reperfusion
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Autophagy in Disease and Therapy
- Allergic Rhinitis and Sensitization
- Phosphodiesterase function and regulation
Sungkyunkwan University
2024
Stanford University
2018-2023
Stanford Medicine
2020
Johns Hopkins Medicine
2013-2017
Johns Hopkins University
2011-2017
RIKEN Center for Integrative Medical Sciences
2015
Medical University of Graz
2014
Triangle
2014
National Institute of Environmental Health Sciences
2014
University of Fukui
2013
To assess physiological and pathophysiological events that involve dynamic interplay between multiple cell types, real-time, in vivo analysis is necessary. We developed a technique based on confocal laser microscopy enabled us to analyze compare the 3-dimensional structures, cellular dynamics, vascular function within mouse lean obese adipose tissue with high spatiotemporal resolution. found increased leukocyte-EC-platelet interaction microcirculation of visceral ob/ob high-fat diet–induced...
Significance Cardiac hypertrophy and dysfunction in response to sustained hormonal mechanical stress are sentinel features of most forms heart disease. Activation non–voltage-gated transient receptor potential canonical channels TRPC3 TRPC6 may contribute this pathophysiology provide a therapeutic target. Effects from combined selective inhibition have not been tested previously. Here we report the capability highly TRPC3/6 inhibitors block pathological hypertrophic signaling several cell...
Pluripotent stem cells (PSCs) offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived exhibit fetal-like characteristics remain immature in a dish. This has emerged as major obstacle their application late-onset diseases. We previously showed that there is neonatal arrest of long-term cultured cardiomyocytes (PSC-CMs). Here, we demonstrate PSC-CMs mature into adult CMs when transplanted hearts. became similar to morphology, structure, function...
The Western pattern diet is rich not only in fat and calories but also phosphate. negative effects of excessive calorie intake on health are widely known, the potential harms phosphate poorly recognized. Here, we show mechanism by which dietary damages kidney. When was relative to number functioning nephrons, circulating levels FGF23, a hormone that increases excretion per nephron, were increased maintain homeostasis. FGF23 suppressed reabsorption renal tubules thus raised concentration...
Rationale: The heart is exquisitely sensitive to mechanical stimuli adapt rapidly physiological demands. In muscle lacking dystrophin, such as Duchenne muscular dystrophy, increased load during contraction triggers pathological responses thought worsen the disease. relevant mechanotransducers and therapies target them remain unclear. Objectives: We tested role of transient receptor potential canonical (TRPC) channels TRPC3 TRPC6 their modulation by protein kinase G (PKG) in controlling...
One of the physiological mechanisms by which heart adapts to a rise in blood pressure is augmenting myocyte stretch-mediated intracellular calcium, with subsequent increase contractility. This slow force response was first described over century ago and has long been considered compensatory, but its underlying link chronic adaptations remain uncertain. Because levels matricellular protein thrombospondin-4 (TSP4) rapidly hypertension are elevated cardiac stress overload failure, we...
Inhibition of cGMP-specific phosphodiesterase 5 (PDE5) ameliorates pathological cardiac remodeling and has been gaining attention as a potential therapy for heart failure. Despite promising results in males, the efficacy PDE5 inhibitor sildenafil female pathologies not determined might be affected by estrogen levels, given hormone's involvement cGMP synthesis. Here, we that heart-protective effect mice depends on presence via mechanism involves myocyte eNOS-dependent synthesis cGMP-dependent...
Adoptive transfer of Tregs has been shown to improve alloengraftment in animal models. However, it is technically challenging expand ex vivo for the purpose infusing large numbers cells clinic. We demonstrate an innovative approach engineering orthogonal IL-2/IL-2 receptor (IL-2R) pair, parts which selectively interact with each other, transmitting native IL-2 signals, but do not natural or IL-2R counterparts, thereby enabling selective stimulation target vivo. Here, we introduced this into...
The proliferation of cardiomyocytes is highly restricted after postnatal maturation, limiting heart regeneration. Elucidation the regulatory machineries for and growth arrest imperative. Chemical biology efficient to dissect molecular mechanisms various cellular events often provides therapeutic potentials. We have been investigating cardiovascular differentiation with pluripotent stem cells. combination cell chemical can provide novel approaches investigate manipulation cardiomyocyte...
Background: Restrictive cardiomyopathy is a rare heart disease associated with mutations in sarcomeric genes and phenotypic overlap hypertrophic cardiomyopathy. There no approved therapy directed at the underlying cause. Here, we explore potential of an interfering RNA (RNAi) therapeutic for human mutation MYL2 causative restrictive mouse model. Methods: A short hairpin (M7.8L) was selected from pool specificity efficacy. Two groups myosin regulatory light chain N47K transgenic mice were...
Mechanical stress is known to alter the electrophysiological properties of myocardium and may trigger fatal arrhythmias when an abnormal load applied heart.We tested hypothesis that structural heterogeneity ventricular wall modulates globally stretches create heterogeneous strain distributions lead initiation arrhythmias.We global arterially perfused rabbit right tissue preparations. The distribution (determined by marker tracking) transmembrane potential (measured optical mapping) were...
All medications have adverse effects. Among the most serious of these are cardiac arrhythmias. Current paradigms for drug safety evaluation costly, lengthy, conservative, and impede efficient development. Here, we combine multiscale experiment simulation, high-performance computing, machine learning to create a risk estimator stratify new existing drugs according their proarrhythmic potential. We capitalize on recent developments in integrate information across 10 orders magnitude space time...
The G protein-coupled receptor APJ is a promising therapeutic target for heart failure. Constitutive deletion of in the mouse protective against hypertrophy-heart failure transition via elimination ligand-independent, β-arrestin-dependent stretch transduction. However, cellular origin this transduction and details its interaction with apelin signaling remain unknown. We generated mice conditional endothelium (APJ
Hypercontractility and arrhythmia are key pathophysiologic features of hypertrophic cardiomyopathy (HCM), the most common inherited heart disease. β-Adrenergic receptor antagonists (β-blockers) first-line therapy for HCM. However, β-blockers commonly selected this disease often poorly tolerated in patients, where heart-rate reduction noncardiac effects can lead to reduced cardiac output fatigue. Mavacamten, myosin ATPase inhibitor recently approved by US Food Drug Administration, has...
ACTN2 (alpha-actinin 2) anchors actin within cardiac sarcomeres. The mechanisms linking
The SARS-CoV-2 pandemic has differentially impacted populations across race and ethnicity. A multi-omic approach represents a powerful tool to examine risk multi-ancestry genomes. We leverage tracking strategy in which we sequence viral host genomes transcriptomes from nasopharyngeal swabs of 1049 individuals (736 positive 313 negative) integrate them with digital phenotypes electronic health records diverse catchment area Northern California. Genome-wide association disaggregated by...
During COVID19 and other viral pandemics, rapid generation of host pathogen genomic data is critical to tracking infection informing therapies. There an urgent need for efficient approaches this at scale. We have developed a scalable, high throughput approach generate fidelity low pass whole genome HLA sequencing, genomes, representation human transcriptome from single nasopharyngeal swabs patients.
Diagnosis of organ transplant rejection relies upon biopsy approaches to confirm alloreactive T cell infiltration in the graft. Immune molecular monitoring is under investigation screen for rejection, though these techniques have suffered from low specificity and lack spatial information. ImmunoPET utilizing antibodies conjugated radioisotopes has potential improve early accurate detection graft rejection. capable noninvasively visualizing dynamic distribution cells expressing specific...
Protein modification by the ubiquitin-like protein ISG15 (ISGylation) plays a crucial role in immunological defense against viral infection. During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, innate immune signaling proteins are ISGylated, facilitating immunity. However, whether SARS-CoV-2 direct substrates for ISGylation remains unclear. In this study, we investigated undergo and affects function. Co-transfection analysis of showed that nucleocapsid (N) is...