A5080115379- Inflammatory Myopathies and Dermatomyositis
- Inflammasome and immune disorders
- Eosinophilic Disorders and Syndromes
- T-cell and B-cell Immunology
- Atrial Fibrillation Management and Outcomes
- Immunodeficiency and Autoimmune Disorders
- Autoimmune and Inflammatory Disorders Research
- Cardiac Arrhythmias and Treatments
- Systemic Lupus Erythematosus Research
- Dermatological and Skeletal Disorders
- Neonatal Respiratory Health Research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Celiac Disease Research and Management
- Reproductive Health and Technologies
- Systemic Sclerosis and Related Diseases
- Innovative Energy Harvesting Technologies
- Ubiquitin and proteasome pathways
- Advanced Sensor and Energy Harvesting Materials
- Ovarian cancer diagnosis and treatment
- Muscle Physiology and Disorders
- interferon and immune responses
- Diverse Approaches in Healthcare and Education Studies
- Dielectric materials and actuators
- Neurogenetic and Muscular Disorders Research
National Institute of Arthritis and Musculoskeletal and Skin Diseases
2015-2025
National Institutes of Health
2012-2025
University of California, San Francisco
2019-2025
University of Michigan
1994-2025
Cleveland Clinic
2023-2024
University of California, Berkeley
2022-2024
George Washington University
2023
Flinders University
2016-2023
Yonsei University
2008-2023
Stroke Association
2021-2023
The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation.
BACKGROUND. Monogenic IFN–mediated autoinflammatory diseases present in infancy with systemic inflammation, an IFN response gene signature, inflammatory organ damage, and high mortality. We used the JAK inhibitor baricitinib, IFN-blocking activity vitro, to ameliorate disease.
Autosomal recessive mutations in proteasome subunit β 8 (PSMB8), which encodes the inducible β5i, cause immune-dysregulatory disease chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE), is classified as a proteasome-associated autoinflammatory syndrome (PRAAS). Here, we identified 4 genes, PSMA3 (encodes α7), PSMB4 β7), PSMB9 β1i), maturation protein (POMP), that have not been previously associated 1 mutation PSMB8 has reported. One patient was...
BACKGROUNDUndifferentiated systemic autoinflammatory diseases (USAIDs) present diagnostic and therapeutic challenges. Chronic interferon (IFN) signaling cytokine dysregulation may identify with available targeted treatments.METHODSSixty-six consecutively referred USAID patients underwent screening for the presence of an signature using a standardized type-I IFN-response-gene score (IRG-S), profiling, genetic evaluation by next-generation sequencing.RESULTSThirty-six (55%) had elevated IRG-S....
PURPOSE Based on preclinical evidence in murine models that interleukin-6 (IL-6) mediates regression of metastatic tumors, we performed a phase I study recombinant human IL-6 patients with refractory advanced malignancies to determine its pharmacokinetics, toxicities, and possible immunologic antitumor effects. PATIENTS AND METHODS Recombinant was administered as single subcutaneous dose daily for 7 days, days off therapy followed by another IL-6. Doses were escalated cohorts three starting...
Abstract Objective To compare the criteria for Wegener's granulomatosis (WG) of American College Rheumatology (ACR) with those European League Against Rheumatism/Pediatric Society (EULAR/PRES) in a cohort children WG and other antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides (AAVs), to describe interval diagnosis, presenting features, initial treatment WG. Methods Eligible patients had been diagnosed by site rheumatologists (termed “MD diagnosis”) since 2004. This diagnosis...
Multiple studies have found an increased prevalence, younger age at onset, and more severe course of glaucoma in people African descent, but these findings are based on conducted outside Africa.
Dielectric elastomers offer the promise of energy harvesting with few moving parts. Power can be produced simply by stretching and contracting a relatively low-cost rubbery material. This simplicity, combined demonstrated high density efficiency, suggests that dielectric are promising for wide range applications. Indeed, have been to harvest from human walking, ocean waves, flowing water, blowing wind, pushing buttons. While technology is promising, there challenges must addressed if...
Motivated by the requirements of mobile manipulation, a compliant underactuated hand, capable locking individual joints, has been developed. Locking is accomplished with electrostatic brakes in joints and significantly increases maximum pullout forces for power grasps. In addition, unlocking hand can adopt configurations grasp sequences that would otherwise require fully actuated solution. Other features include an integrated sensing suite uses common transduction technology on flexible...
Chronic elevation of interferon (IFN)-response genes (IRG) in a subset patients with systemic immune-dysregulatory diseases, including the Mendelian Type-I IFN-mediated autoinflammatory diseases and some autoimmune suggest causative role excessive IFN signaling disease pathogenesis as target for treatment. We developed 28-IFN response gene scoring system to calculate either standardized or geomean score by customizing NanoString assay quantify expression putative IRGs. The targets were...
Population pharmacokinetic (popPK) modeling was used to characterize the PK profile of oral Janus kinase (JAK)1/JAK2 inhibitor, baricitinib, in 18 patients with Mendelian interferonopathies who are enrolled a compassionate use program. Patients received doses between 0.1 17 mg per day. Covariates weight and renal function significantly influenced volume-of-distribution clearance, respectively. The half-life baricitinib less than 40 kg substantially shorter adult populations, requiring need...
Dicationic 2,5-bis(4-guanidinophenyl)furans 5a−5f, 2,5-bis[4-(arylimino)aminophenyl]furans 6a−6b and 6e−6k, 2,5-bis[4-(alkylimino)aminophenyl]furans 6c−6d have been synthesized starting from 2,5-bis[tri-n-butylstannyl]furan. Thermal melting studies with poly dA•dT the duplex oligomer d(CGCGAATTCGCG)2 demonstrated high DNA binding affinities for a number of compounds. The are highly dependent on structure significantly affected by substituents both phenyl rings 2,5-diphenylfuran nucleus...
Abstract Prostate cancer is the most common among men in United States, and aberrant DNA methylation known to be an early molecular event its development. Here, we have used expression profiling identify novel hypermethylated genes whose induced by treatment of prostate cell lines with methyltransferase inhibitor 5-Aza-2′-deoxycytidine (5-aza-dC). Of 271 that were 5-aza-dC treatment, 25 also displayed reduced primary tumors compared normal tissue, decreased only one gene, aldehyde...
Identifying functionally critical regions of the malaria antigen AMA1 (apical membrane 1) is necessary to understand significance polymorphisms within this for vaccine development. The crystal structure in complex with Fab fragment inhibitory monoclonal antibody 1F9 reveals that binds solvent-exposed hydrophobic trough, confirming its importance. uses heavy and light chain complementarity-determining (CDRs) wrap around polymorphic loops adjacent but a ridge framework residues bind trough....
Drug-induced haploinsufficiency (DIH) in yeast has been considered a valuable tool for drug target identification. A plant metabolite, plumbagin, potent anticancer activity via reactive oxygen species (ROS) generation. However, the detailed molecular targets of plumbagin ROS generation are not understood. Here, using DIH and heterozygous deletion mutants fission Schizosaccharomyces pombe, we identified 1, 4-phopshatidylinositol 5-kinase (PI5K) its3 as new Plumbagin showed anti-proliferative...
Abstract Background Juvenile dermatomyositis (JDM) is a systemic autoimmune disease with prominent interferon (IFN) signature, but the pathogenesis of JDM and etiology its IFN signature remain unknown. The Mendelian autoinflammatory interferonopathies, Chronic Atypical Neutrophilic Dermatosis Lipodystrophy Elevated temperature (CANDLE) STING-Associated Vasculopathy onset in Infancy (SAVI), are caused by genetic mutations have extremely elevated signatures thought to drive pathology....