A5074614441- Cardiac electrophysiology and arrhythmias
- Cardiomyopathy and Myosin Studies
- RNA and protein synthesis mechanisms
- Atrial Fibrillation Management and Outcomes
- Cardiac Arrhythmias and Treatments
- Catalytic Cross-Coupling Reactions
- RNA Research and Splicing
- Ion channel regulation and function
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- CRISPR and Genetic Engineering
- Cardiac pacing and defibrillation studies
- Genomics and Rare Diseases
- Catalytic C–H Functionalization Methods
- Cardiovascular Effects of Exercise
- ECG Monitoring and Analysis
- Neuroscience and Neural Engineering
- Advanced Synthetic Organic Chemistry
- Pluripotent Stem Cells Research
- Mitochondrial Function and Pathology
- Chemical synthesis and alkaloids
- Viral Infections and Immunology Research
- Fluorine in Organic Chemistry
- Sulfur-Based Synthesis Techniques
- Health Systems, Economic Evaluations, Quality of Life
Vanderbilt University
2021-2025
Vanderbilt University Medical Center
2019-2025
Brigham and Women's Hospital
2025
King's College London
2012-2024
St Thomas' Hospital
2023-2024
Saint Thomas Health
2024
University of Notre Dame
2021
Max-Planck-Institut für Kohlenforschung
2018
Tarbiat Modares University
2018
Universidad de Los Andes
2018
Early-onset atrial fibrillation (AF) can be the initial manifestation of a more serious underlying inherited cardiomyopathy or arrhythmia syndrome.
Abstract Suzuki, Negishi, and Kumada couplings are some of the most important reactions for formation skeletal C−C linkages. Their widespread use to forge bonds between two aromatic rings has enabled every branch chemical science. The analogous union alkyl halides metallated aryl systems not been as widely employed due lack commercially available halide building blocks. Redox‐active esters have recently emerged useful surrogates in cross‐coupling chemistry. Such easily accessible through...
The functionalization of aminoheterocycles by using a pyrylium tetrafluoroborate reagent (Pyry-BF4 ) is presented. This efficiently condenses with great variety heterocyclic amines and primes the C-N bond for nucleophilic aromatic substitution. More than 60 examples formation C-O, C-N, C-S, or C-SO2 R bonds are disclosed herein. In contrast to activation through diazotization polyalkylation, this method characterized its mild conditions impressive functional-group tolerance. addition...
Patients with early-onset atrial fibrillation (AF) are enriched for rare variants in cardiomyopathy and arrhythmia genes. The clinical significance of these patients AF is unknown.
Presented herein is a general protocol for the alkylation of simple aryl fluorides with unbiased secondary Grignard reagents by means nickel catalysis. This study revealed Thorpe-Ingold effect in ligand backbone which confers high degree selectivity carbon center C-C coupling event. characterized mild reaction conditions, robustness, and simplicity. Both electron-rich electron-deficient are suitable candidates this transformation. Equally amenable variety heterocycles, permitting without...
Suzuki, Negishi, and Kumada couplings are some of the most important reactions for formation skeletal C−C linkages. Their widespread use to forge bonds between two aromatic rings has enabled every branch chemical science. The analogous union alkyl halides metallated aryl systems not been as widely employed due lack commercially available halide building blocks. Redox-active esters have recently emerged useful surrogates in cross-coupling chemistry. Such easily accessible through ubiquitous...
Abstract Rare missense variants are often classified as of uncertain significance (VUS) due to insufficient evidence for classification. These ambiguous findings create anxiety and frequently lead inappropriate workup, colloquially referred the ‘diagnostic odyssey’. Well-validated high-throughput experimental data have potential significantly reduce number VUS identified by clinical genetic testing, though extent this reduction optimal strategies achieve it remain unclear. 1
Importance Filamin C truncating variants (FLNCtv) are a rare cause of cardiomyopathy with heterogeneous phenotypic presentations. Despite high incidence life-threatening ventricular arrhythmias and sudden cardiac death (SCD), reliable risk predictors to stratify carriers FLNCtv lacking. Objective To determine factors predictive SCD/major (MVA) in FLNCtv. Design, Setting, Participants This was an international, multicenter, retrospective cohort study conducted from February 2023 June 2024....
Background: Brugada Syndrome (BrS) is an inherited arrhythmia disorder that causes elevated risk of sudden cardiac death. Approximately 20% patients with BrS have rare variants in SCN5A, which encodes the sodium channel Na V 1.5. Genetic workup often complicated by SCN5A uncertain significance (VUS) and/or incomplete penetrance. Methods: We analyzed all 252 missense and in-frame insertion/deletion from a previously published large cohort cases (n=3,335 patients) using calibrated...
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is strongly associated with rare missense variants in RYR2 , the gene encoding intracellular calcium release channel RyR2. Precision medicine complicated by incomplete penetrance, particularly case of -CPVT variants. To improve structural understanding and clinical actionability RYR2- CPVT penetrance. We curated 179 manuscripts reviewed three individuals to extrapolate variant genotype-phenotype relationships. Purportedly neutral...
A burgeoning family of p53-related genes have been described recently, including p73 and p63. Both these encode proteins with many similarities to p53 but also the potential for forming a range related species by alternative promoter usage splicing. In order begin characterization p63, we generated polyclonal serum (designated SC1) that recognizes C-terminus p63α. We shown this reagent p63α not nor p73. By western blot analysis both N-terminal truncated form (ΔNp63α) were found in cell...
BACKGROUND: Long QT syndrome is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded KCNH2 . Variant classification difficult, often because of lack functional data. Moreover, variant-based risk stratification also complicated heterogenous clinical data and incomplete penetrance. Here we sought to test whether variant-specific information, primarily from high-throughput assays, could improve both cardiac event large, harmonized...
Abstract The functionalization of aminoheterocycles by using a pyrylium tetrafluoroborate reagent (Pyry‐BF 4 ) is presented. This efficiently condenses with great variety heterocyclic amines and primes the C−N bond for nucleophilic aromatic substitution. More than 60 examples formation C−O, C−N, C−S, or C−SO 2 R bonds are disclosed herein. In contrast to activation through diazotization polyalkylation, this method characterized its mild conditions impressive functional‐group tolerance....
Rare protein-altering variants in SCN5A, KCNQ1, and KCNH2 are major causes of Brugada syndrome the congenital long QT syndrome. While splice-altering lying outside 2-bp canonical splice sites can cause these diseases, their role remains poorly described. We implemented 2 functional assays to assess 12 recently reported putative uncertain significance 1 likely pathogenic variant without data observed probands.We deployed minigene splicing consequences 10 variants. Three incompatible with...
Abstract Background We identified a novel SCN5A variant, E171Q, in neonate with very frequent ectopy and reduced ejection fraction which normalized after arrhythmia suppression by flecainide. This clinical picture is consistent multifocal ectopic Purkinje-related premature contractions (MEPPC). Most previous reports of MEPPC have implicated variants such as R222Q that neutralize positive charges the S4 voltage sensor helix channel protein Na V 1.5 generate gating pore current. Methods...
While the advent of transition-metal catalysis has undoubtedly transformed synthetic chemistry, problems persist with introduction secondary and tertiary alkyl nucleophiles into C(sp2) aryl electrophiles. Complications arise from delicate organometallic intermediates typically invoked by such processes, which competition between desired reductive elimination event deleterious β-H pathways can lead to undesired isomerization incoming nucleophile. Several methods have integrated distinct...
Background: The proliferation of genetic profiling has revealed many associations between variations and disease. However, large-scale phenotyping efforts in largely healthy populations, coupled with DNA sequencing, suggest variants currently annotated as pathogenic are more common populations than previously thought. In addition, novel rare frequently observed genes associated disease both individuals those under suspicion This raises the question whether these can be useful predictors To...
BACKGROUND: Brugada syndrome is an inheritable arrhythmia condition that associated with rare, loss-of-function variants in SCN5A . Interpreting the pathogenicity of missense challenging, and ≈79% ClinVar are currently classified as uncertain significance. Automated patch clamp technology enables high-throughput functional studies ion channel can provide evidence for variant reclassification. METHODS: An vitro –Brugada automated assay was independently performed at Vanderbilt University...
This study uses health plan price transparency data to examine how negotiated rates for the same service vary within and across US payers hospitals.