A5091829136- Cardiac electrophysiology and arrhythmias
- Ocular Oncology and Treatments
- Ion channel regulation and function
- Atrial Fibrillation Management and Outcomes
- Cardiomyopathy and Myosin Studies
- Cutaneous Melanoma Detection and Management
- Retinal Development and Disorders
- RNA regulation and disease
- Immunotherapy and Immune Responses
- Nonmelanoma Skin Cancer Studies
- Cancer-related molecular mechanisms research
- 14-3-3 protein interactions
- ATP Synthase and ATPases Research
- Cardiovascular Function and Risk Factors
- Cerebrovascular and genetic disorders
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- MicroRNA in disease regulation
- Takotsubo Cardiomyopathy and Associated Phenomena
- Circular RNAs in diseases
- Peptidase Inhibition and Analysis
- RNA Research and Splicing
- Inflammasome and immune disorders
- Redox biology and oxidative stress
- Microtubule and mitosis dynamics
Baylor College of Medicine
2014-2023
University of Illinois Chicago
2019-2020
Houston Methodist
2014
Essen University Hospital
2014
University of Duisburg-Essen
2014
University of St. Thomas - Texas
2013
Atrial fibrillation (AF) is frequently associated with enhanced inflammatory response. The NLRP3 (NACHT, LRR, and PYD domain containing protein 3) inflammasome mediates caspase-1 activation interleukin-1β release in immune cells but not known to play a role cardiomyocytes (CMs). Here, we assessed the of CM AF.
Enhanced sarcoplasmic reticulum Ca(2+)-leak via ryanodine receptor type-2 (RyR2) contributes to the pathogenesis of atrial fibrillation (AF). Recent studies have shown that level RyR2 protein is elevated in atria patients with paroxysmal AF, suggesting microRNA-mediated post-transcriptional regulation might be an underlying mechanism. Bioinformatic analysis suggests miR-106b and miR-93, members miR-106b-25 cluster, could bind RyR2-3'-untranslated region suppress its translation. Thus, we...
Enhanced diastolic calcium (Ca2+) release through ryanodine receptor type-2 (RyR2) has been implicated in atrial fibrillation (AF) promotion. Diastolic sarcoplasmic reticulum Ca2+ leak is caused by increased RyR2 phosphorylation PKA (protein kinase A) or CaMKII (Ca2+/calmodulin-dependent kinase-II) phosphorylation, less dephosphorylation protein phosphatases. However, considerable controversy remains regarding the molecular mechanisms underlying altered function AF. We thus aimed to...
Rationale: Somatic overexpression in mice using an adeno-associated virus (AAV) as gene transfer vectors has become a valuable tool to analyze the roles of specific genes cardiac diseases. The lack atrial-specific AAV vector been major obstacle for studies into pathogenesis atrial Moreover, therapy fibrillation would benefit from vectors. Atrial natriuretic factor (ANF) promoter drives expression specifically cardiomyocytes. Objective: To establish platform vivo delivery by AAV-ANF. Methods...
Abnormal calcium (Ca2+) release from the sarcoplasmic reticulum (SR) contributes to pathogenesis of atrial fibrillation (AF). Increased phosphorylation 2 proteins essential for normal SR-Ca2+ cycling, type-2 ryanodine receptor (RyR2) and phospholamban (PLN), enhances susceptibility AF, but underlying mechanisms remain unclear. Protein phosphatase 1 (PP1) limits steady-state both RyR2 PLN. Proteomic analysis uncovered a novel PP1-regulatory subunit (PPP1R3A [PP1 regulatory type 3A]) in...
Altered Ca2+ handling in atrial fibrillation (AF) has been associated with dysregulated protein phosphatase 1 (PP1) and subcellular heterogeneities phosphorylation, but the underlying mechanisms remain unclear. This is due to a lack of investigation into local, rather than global, regulation PP1 on different targets such as ryanodine receptor type 2 (RyR2), especially AF. We tested hypothesis that impaired local causes RyR2 hyperphosphorylation thereby promoting AF susceptibility. To...
Abstract Background Cardiac hypertrophy and heart failure are characterized by increased late sodium current abnormal Ca 2+ handling. Ranolazine, a selective inhibitor of the current, can reduce accumulation overload. In this study, we investigated effects ranolazine on pressure overload‐induced cardiac in mice. Methods Results Inhibition with suppressed fibrosis improved function assessed echocardiography, hemodynamics, histological analysis mice exposed to chronic overload induced...
The prognostic 15-gene expression profile (15-GEP) test for uveal melanoma (UM) predicts metastatic risk based on primary tumor biology. Here we report outcomes from a prospective registry of 15-GEP-tested patients, and meta-analysis with published cohorts.Management 5-year clinical following 15-GEP testing were evaluated.Eighty-nine patients results prospectively enrolled at four centers. Physician-recommended management plans collected, tracked every 6 months.Eighty percent Class 1...
Voltage-gated Na
We have previously demonstrated that type II ryanodine receptors (RyR2) tetramers can be rapidly rearranged in response to a phosphorylation cocktail. The cocktail modified downstream targets indiscriminately, making it impossible determine whether of RyR2 was an essential element the response. Here, we used β-agonist isoproterenol and mice homozygous for one following clinically relevant mutations: S2030A, S2808A, S2814A, or S2814D. measured length dyad using transmission electron...
Background The sodium channel, Nav1.5, encoded by SCN 5A, undergoes developmentally regulated splicing from inclusion of exon 6A in the fetal heart to 6B adults. These mutually exclusive exons differ 7 amino acids altering electrophysiological properties Nav1.5 channel. In myotonic dystrophy type 1, 5A is mis-spliced such that pattern detected adult hearts. Cardiac manifestations 1 include conduction defects and arrhythmias are second-leading cause death. Methods Results This work aimed...
Abstract Purpose: With a prevalence of approximately 5% in the U.S., uveal melanocytic tumors indeterminate malignant potential (UMTIMP) are primarily managed by observation for growth prior to treatment. While these lesions can be assessed intraocular tumor biopsy and genetic testing, serial operating room is not feasible routine management UMTIMPs. On other hand, aqueous humor (AH) from anterior chamber eye easily safely obtained an office-based procedure that repeated periodically....
Spontaneously depolarizing nodal cells comprise the pacemaker of heart. Intracellular calcium (Ca
Heart failure (HF) is a complex disease with rising prevalence despite advances in treatment. Protein phosphatase 1 (PP1) has long been implicated HF pathogenesis, but its exact role both unclear and controversial. Most previous studies measured only the PP1 catalytic subunit (PP1c) without investigating diverse set of interactors, which confer localization substrate specificity to holoenzyme. In this study, we define interactome cardiac tissue test hypothesis that becomes rearranged during...
The Clinical Application of DecisionDx-UM Gene Expression Assay Results study aimed to evaluate the clinical utility prognostic 15-gene expression profile (15-GEP) test for uveal melanoma (UM) patients in a large, prospective multicenter cohort.Nine centers prospectively enrolled 138 UM clinically tested with 15-GEP. Physician-recommended specialty referrals and metastatic surveillance regimens were collected.A total 93% high-risk class 2 referred medical oncology follow-up, compared 51% 1...
This study explored uveal melanoma patient experiences and regret following molecular prognostic testing using a 15-gene expression profile (GEP) test. A retrospective, cross-sectional survey was conducted through an online questionnaire capturing patient-reported with biopsy/molecular testing. Of 177 respondents, 159 (90%) wanted information at diagnosis. Most 15-GEP-tested patients who shared their results (99%) reported gaining value from testing, as did tested other methods. Patients...
Abstract Long QT syndrome (LQTS) is a genetic disease resulting in prolonged interval on resting electrocardiogram, predisposing affected individuals to polymorphic ventricular tachycardia and sudden death. Although number of genes have been implicated this disease, nearly one four exhibiting the LQTS phenotype are genotype‐negative. Whole‐exome sequencing identified missense T223M variant TBX5 that cosegregates with family otherwise genotype‐negative The TBX5‐T223M was absent among large...
<b><i>Introduction:</i></b> Gene expression profiling (GEP) is widely used for prognostication in patients with uveal melanoma (UM). Because biopsy tissue limited, it critical to obtain as much genomic information possible from each sample. Combined application of both GEP and next-generation sequencing (NGS) allows analysis RNA DNA a single sample, offers additional prognostic information, can potentially inform therapy selection. This study evaluated the analytical...
9598 Background: The 15-gene expression profile (15-GEP) test is the gold standard in US for metastatic risk prediction uveal melanoma (UM). Studies have shown that 15-GEP superior to and independent of other clinicopathologic molecular factors, including PRAME status BAP1 mutation status. Supplemental tests 7-gene NGS panel ( BAP1, SF3B1, EIF1AX, GNA11, GNAQ, CYSLTR2, PLCB4)are validated can now be run clinically from same biopsy specimen. However, discordance between 15-GEP, clinical...