A5091218113- Nutrition and Health in Aging
- Cancer-related molecular mechanisms research
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Corneal surgery and disorders
- Gene expression and cancer classification
- Intensive Care Unit Cognitive Disorders
- Glaucoma and retinal disorders
- Kawasaki Disease and Coronary Complications
- T-cell and B-cell Immunology
- Coronary Artery Anomalies
- Muscle Physiology and Disorders
- Bioinformatics and Genomic Networks
- Retinal Diseases and Treatments
- Lipid metabolism and disorders
- IL-33, ST2, and ILC Pathways
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Peroxisome Proliferator-Activated Receptors
- Prion Diseases and Protein Misfolding
- Mechanical Circulatory Support Devices
- Genetic Associations and Epidemiology
- Bayesian Modeling and Causal Inference
- Whipple's Disease and Interleukins
- CNS Lymphoma Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
Regeneron (United States)
2008-2022
ORCID
2021
Rady Children's Hospital-San Diego
2010-2016
Cedars-Sinai Medical Center
2016
University of California, Los Angeles
2016
Hospital for Special Surgery
2016
Cornell University
2016
The University of Tokyo
2016
University of California, San Diego
2016
Genome Institute of Singapore
2010
The expansion of a hexanucleotide (GGGGCC) repeat in C9ORF72 is the most common cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both function mechanism by which drives neuropathology are unknown. To examine whether haploinsufficiency induces neurological disease, we created C9orf72-deficient mouse line. Null mice developed robust immune phenotype characterized myeloid expansion, T cell activation, increased plasma cells. Mice also presented with elevated...
Growth and differentiation factor 8 (GDF8) is a TGF-β superfamily member, negative regulator of skeletal muscle mass. GDF8 inhibition results in prominent growth mice, but less impressive hypertrophy primates, including man. Broad suggests another family member negatively regulates mass, its blockade enhances seen with GDF8-specific inhibition. Here we show that activin A the long-sought second regulator. Activin specific inhibition, on top leads to pronounced force production mice monkeys....
Transforming growth factor (TGF)-β is a multifunctional peptide that important in T-cell activation and cardiovascular remodeling, both of which are features Kawasaki disease (KD). We postulated variation TGF-β signaling might be KD susceptibility outcome.We investigated genetic 15 genes belonging to the pathway total 771 subjects mainly European descent from United States, Kingdom, Australia, Netherlands. analyzed transcript abundance patterns using microarray reverse...
Accurate HLA typing at amino acid level (four-digit resolution) is critical in hematopoietic and organ transplantations, pathogenesis studies of autoimmune infectious diseases, as well the development immunoncology therapies. With rapid adoption genome-wide sequencing biomedical research, based on transcriptome whole exome/genome data becomes increasingly attractive due to its high throughput convenience. However, unlike targeted amplicon sequencing, often employs a reduced read length...
The conventional outflow pathway is a complex tissue responsible for maintaining intraocular pressure (IOP) homeostasis. coordinated effort of multiple cells with differing responsibilities ensures healthy function and IOP maintenance. Dysfunction one or more resident cell types results in ocular hypertension risk glaucoma, leading cause blindness. In this study, single-cell RNA sequencing was performed to generate comprehensive atlas human tissues. We obtained expression profiles 17,757...
Kawasaki disease (KD) is the most common cause of acquired cardiac in US children. In addition to coronary artery abnormalities and aneurysms, it can be associated with systemic arterial aneurysms. We evaluated development dilatation including abdominal aortic aneurysm (AAA) Lactobacillus casei cell-wall extract (LCWE)-induced KD vasculitis mouse model.We discovered that aortitis, arteritis myocarditis, LCWE-induced model also aorta AAA, as well renal iliac AAA induced mice was exclusively...
BackgroundSevere inflammatory airway diseases are associated with inflammation that does not resolve, leading to structural changes and an overall environment primed for exacerbations.ObjectiveWe sought identify inhibit pathways perpetuate this heightened state because could lead therapies allow a more quiescent lung is less predisposed symptoms exacerbations.MethodsUsing prolonged exposure house dust mite in mice, we developed mouse model of persistent exacerbating disease characterized by...
When the same set of genes appear in two top ranking gene lists different studies, it is often interest to estimate probability for this being a chance event. This overlapping well known follow hypergeometric distribution. Usually, lengths top-ranking are assumed be fixed, by using pre-set criterion on, e.g., p-value t-test. We investigate how changes with selection criterion, or simply, length lists. It concluded that indeed function list length, and its statistical significance should...
To characterize the safety, tolerability, and anti-tumor activity of cemiplimab as monotherapy or in combination with hypofractionated radiation therapy (hfRT) patients recurrent metastatic cervical cancer. determine association between histology programmed death-ligand 1 (PD-L1) expression.In non-randomized phase I expansion cohorts, (squamous non-squamous histology) received 3 mg/kg intravenously every 2 weeks for 48 weeks, either alone (monotherapy cohort) hfRT during week (combination...
Abstract Bulk RNA sequencing of a tissue captures the gene expression profile from all cell types combined. Single-cell identifies discrete cell-signatures based on transcriptomic identities. Six adult human corneas were processed for single-cell RNAseq and 16 clusters bioinformatically identified. Based their signatures RNAscope results using representative cluster marker genes cornea cross-sections, these confirmed to be stromal keratocytes, endothelium, several subtypes corneal...
The microtubule-associated protein tau is an abundant component of neurons the central nervous system. In Alzheimer's disease and other neurodegenerative tauopathies, found hyperphosphorylated aggregated in neurofibrillary tangles. To obtain a better understanding cellular perturbations that initiate pathogenesis, we performed CRISPR-Cas9 screen for genetic modifiers enhance aggregation. This initial yielded three genes, BANF1, ANKLE2, PPP2CA, whose inactivation promotes accumulation...
Critical illness myopathy (CIM) is associated with severe skeletal muscle wasting and impaired function in intensive care unit (ICU) patients. The mechanisms underlying CIM remain incompletely understood. To elucidate the biological activities occurring at transcriptional level of ICU patients CIM, gene expression profiles, potential upstream regulators, enrichment pathways were characterized using RNA sequencing (RNA-seq). We also compared signatures genes perturbed by mechanical loading...
Using an experimental rat intensive care unit (ICU) model, not limited by early mortality, we have previously shown that passive mechanical loading attenuates the loss of muscle mass and force-generation capacity associated with ICU intervention. Mitochondrial dynamics recently been to play a more important role in atrophy than recognized. In this study demonstrate mitochondrial dynamics, as well mitophagy, is affected mechanosensing at transcriptional level, changes induced unloading are...
Background and Purpose: Stroke is a major cause of chronic neurological disability. There considerable interest in understanding how acute transcriptome changes evolve into subacute patterns that facilitate or limit spontaneous recovery. Here we mapped longitudinal gene expression at multiple time points after stroke mice out to 6 months. Methods: Adult C57BL/6 were subjected transient middle cerebral artery occlusion. Longitudinal levels measured 10 from recovery phases ischemic stroke....
Unrestrained IL-36R signaling in a humanized mouse model causes barrier impairment and increased cutaneous intestinal inflammation.
Glaucoma is a leading cause of blindness. Current glaucoma medications work by lowering intraocular pressure (IOP), risk factor for glaucoma, but most treatments do not directly target the pathological changes to increased IOP, which can manifest as medication resistance disease progresses. To identify physiological modulators we performed genome- and exome-wide association analysis in >129,000 individuals with IOP measurements extended these findings an risk. We report identification...
Abstract Bulk RNA sequencing provides the opportunity to understand biology at whole transcriptome level without prohibitive cost of single cell profiling. Advances in spatial transcriptomics enable dissect tissue organization and function by genome-wide gene expressions. However, readout both technologies is overall expression across potentially many types directly providing information type constitution. Although several in-silico approaches have been proposed deconvolute RNA-Seq data...
The Adisintegrin and metalloprotease domain-containing (ADAM) family of proteins is involved in cell adhesion, migration, proteolysis, signaling. Many ADAMs are required for reproduction; however, the role Adam6 has remained largely unknown. In course humanizing mouse immunoglobulin heavy chain (IgH) locus, we generated Adam6-deficient mice that demonstrate severe subfertility. We decided to elucidate ADAM6 fertility explore underlying mechanisms. Despite normal sperm development motility,...
Abstract Aim Muscle wasting is one of the factors most strongly predicting mortality and morbidity in critically ill intensive care unit ( ICU ). This muscle affects both limb respiratory muscles, but understanding underlying mechanisms muscle‐specific differences remains incomplete. study aimed at investigating temporal expression phosphorylation Janus kinase/signal transducer activator transcription JAK / STAT ) pathway associated with condition to characterize proteins related changes...
Profiling T cell receptor (TCR) repertoire via short read transcriptome sequencing (RNA-Seq) has a unique advantage of probing simultaneously TCRs and the genome-wide RNA expression other genes. However, compared to targeted amplicon approaches, shorter length is more prone mapping error. In addition, only small percentage reads may cover TCR loci thus could be significantly under-sampled. Although this approach been applied in few studies, utility repertoires not evaluated extensively. Here...
When the same set of genes appear in two top ranking gene lists different studies, it is often interest to estimate probability for this being a chance event. This overlapping well known follow hypergeometric distribution. Usually, lengths top-ranking are assumed be fixed, by using pre-set criterion on, e.g., p-value t-test. We investigate how changes with selection criterion, or simply, length lists. It concluded that indeed function list length, and its statistical significance should...