A5016689555- Cardiac electrophysiology and arrhythmias
- Cutaneous Melanoma Detection and Management
- Ion channel regulation and function
- Melanoma and MAPK Pathways
- Cardiomyopathy and Myosin Studies
- Dermatology and Skin Diseases
- CAR-T cell therapy research
- Cardiovascular Effects of Exercise
- Atrial Fibrillation Management and Outcomes
- Nonmelanoma Skin Cancer Studies
- Receptor Mechanisms and Signaling
- Cutaneous lymphoproliferative disorders research
- Asthma and respiratory diseases
- Transgenic Plants and Applications
- Monoclonal and Polyclonal Antibodies Research
- Multiple Sclerosis Research Studies
- Electrochemical Analysis and Applications
- Allergic Rhinitis and Sensitization
- Psoriasis: Treatment and Pathogenesis
- Biotin and Related Studies
- Pulmonary Hypertension Research and Treatments
- Erythrocyte Function and Pathophysiology
- Muscle Physiology and Disorders
- Autoimmune and Inflammatory Disorders
- Immunotherapy and Immune Responses
Baylor College of Medicine
2014-2024
Cardiovascular Institute Hospital
2018-2024
Bioscience (China)
2021
Harvard University
2018
Johns Hopkins University
2018
University of Houston
2016
Utrecht University
2016
Rationale: Junctional membrane complexes (JMCs) in myocytes are critical microdomains, which excitation–contraction coupling occurs. Structural and functional disruption of JMCs underlies contractile dysfunction failing hearts. However, the role newly identified JMC protein SPEG (striated muscle preferentially expressed kinase) remains unclear. Objective: To determine healthy adult Methods Results: Proteomic analysis immunoprecipitated proteins ryanodine receptor type 2 junctophilin-2 (JPH2)...
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...
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...
National guidelines recommend sentinel lymph node biopsy (SLNB) be offered to patients with > 10% likelihood of (SLN) positivity. On the other hand, do not SLNB for T1a tumors without high-risk features who have < 5% a positive SLN. However, decision perform is less certain higher-risk T1 melanomas in which expected 5%-10% time. We hypothesized that integrating clinicopathologic 31-gene expression profile (31-GEP) score using advanced artificial intelligence techniques would provide more...
Signalling nanodomains requiring close contact between the plasma membrane and internal compartments, known as 'junctions', are fast communication hubs within excitable cells such neurones muscle. Here, we have examined two transgenic murine models probing role of junctophilin-2, a membrane-tethering protein crucial for formation molecular organisation sub-microscopic junctions in ventricular muscle heart. Quantitative single-molecule localisation microscopy showed that animals producing...
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...
Current guidelines for postoperative management of patients with stage I-IIA cutaneous melanoma (CM) do not recommend routine cross-sectional imaging, yet many these develop metastases. Methods that complement American Joint Committee on Cancer (AJCC) staging are needed to improve identification and treatment patients. A 31-gene expression profile (31-GEP) test predicts metastatic risk as low (class 1) or high 2). Prospective analysis CM outcomes was performed the hypotheses 31-GEP provides...
Background: Duchenne muscular dystrophy patients are prone to ventricular arrhythmias, which may be caused by abnormal calcium (Ca 2+ ) homeostasis and elevated reactive oxygen species. CaMKII /calmodulin-dependent protein kinase II) is vital for normal Ca homeostasis, but excessive activity contributes arrhythmias in cardiomyocytes. Reactive species induce become autonomously active. We hypothesized that genetic inhibition of oxidation (ox-CaMKII) a mouse model can alleviate thus,...
Ryanodine receptors (RyRs) exhibit dynamic arrangements in cardiomyocytes, and we previously showed that ‘dispersion’ of RyR clusters disrupts Ca 2+ homeostasis during heart failure (HF) (Kolstad et al., eLife, 2018). Here, investigated whether prolonged β-adrenergic stimulation, a hallmark HF, promotes cluster dispersion examined the underlying mechanisms. We observed treatment healthy rat cardiomyocytes with isoproterenol for 1 hr triggered progressive fragmentation clusters....
Myocardial lipid metabolism is critical to normal heart function, whereas altered regulation has been linked cardiac diseases including cardiomyopathies. Genetic variants in the JPH2 gene can cause hypertrophic cardiomyopathy (HCM) and, some cases, dilated (DCM). In this study, we tested hypothesis that identified patients with HCM and DCM, respectively, distinct alterations myocardial profiles. Echocardiography revealed clinically significant dysfunction both knock-in mouse models of...
National Comprehensive Cancer Network (NCCN) guidelines for cutaneous melanoma (CM) recommend physicians consider increased surveillance patients who typically have lower survival rates (stages IIB-IV as determined by the American Joint Committee on (AJCC), 8th edition). However, up to 15% of identified having a low recurrence risk I-IIA) experience disease recurrence, and some high will not any recurrence. The 31-gene expression profile test (31-GEP) stratifies patient into (Class 1) 2) has...
Empirical decisions to select therapies for psoriasis (PSO) and atopic dermatitis (AD) can lead delays in disease control increased health care costs. However, routine molecular testing AD PSO are lacking.
Background: Recent advances in understanding the molecular mechanisms underlying atopic dermatitis (AD) have led to development and FDA approval of multiple targeted therapies. Molecular heterogeneity AD contributes inconsistent clinical presentation therapeutic response, which can lead delays diagnosis initiation appropriate treatment for patients. Adding complexity decision-making process, newer systemic treatments are also associated with varied efficacy, safety profiles, monitoring...
Junctophilin-2 (JPH2) is a structural calcium (Ca2+) handling protein, which approximates the cardiomyocyte transverse tubules (TTs) to sarcoplasmic reticulum. This facilitates communication of voltage-gated Ca2+ channel and ryanodine receptor RyR2. A human patient with hypertrophic cardiomyopathy was positive for JPH2 mutation substituting alanine-405—located within alpha helix domain—with serine (A405S). Using novel mouse echocardiography plane, we found that mice bearing this developed...
Abstract Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac arrhythmia syndrome that often leads to sudden death. The most common form of CPVT caused by autosomal‐dominant variants in the ryanodine receptor type‐2 ( RYR2) gene. Mutations RYR2 promote calcium (Ca 2+ ) leak from sarcoplasmic reticulum (SR), triggering lethal arrhythmias. Recently, it was demonstrated tetracaine derivative EL20 specifically inhibits mutant RyR2, normalizes Ca handling and...
Framingham Heart Study suggests that dysfunction of steroid receptor coactivator-1 may be involved in the development hypertension. However, there is no functional evidence linking to regulation blood pressure. We used immunohistochemistry map expression protein mouse brain, especially regions implicated Steroid was found central amygdala, medial supraoptic nucleus, arcuate ventromedial, dorsomedial, paraventricular hypothalamus, and nucleus solitary tract. To determine effects on...
Aim: Sentinel node biopsy is a prognostic indicator of melanoma recurrence. We hypothesized that adding the primary molecular signature from 31-gene expression profile (31-GEP) test could refine risk recurrence prognosis for patients with stage I-III melanoma. Materials & methods: Four hundred thirty-eight consecutively tested 31-GEP were retrospectively analyzed. The stratified as low-risk (Class 1A), intermediate-risk 1B/2A) or high 2B) metastasis. Results: significantly patient...
Fifteen to forty percent of patients with localized cutaneous melanoma (CM) (stages I-II) will experience disease relapse. The 31-gene expression profile (31-GEP) uses gene data from the primary tumor in conjunction clinicopathologic features refine patient prognosis. study's objective was evaluate 31-GEP risk stratification for disease-free survival (DFS) a previously published cohort longer follow-up.Patients stage IB-II CM (n = 86) were prospectively tested 31-GEP. Follow-up time...
BackgroundThere is a need to improve prognostic accuracy for patients with cutaneous melanoma. A 31-gene expression profile (31-GEP) test uses the molecular biology of primary tumors identify individual patient metastatic risk.ObjectiveDevelop nomogram incorporating 31-GEP relevant clinical factors accuracy.MethodsIn an IRB-approved study, 1124 from 9 Mohs micrographic surgery centers were prospectively enrolled, treated surgery, and underwent testing. Data 684 those at least 1-year...
Cutaneous melanoma (CM) survival is assessed using averaged data from the American Joint Committee on Cancer 8th edition (AJCC8). However, subsets of AJCC8 stages I–III have better or worse than predicted average value. The objective this study was to determine if 31-gene expression profile (31-GEP) test for CM can further risk-stratify melanoma-specific mortality within each stage. This retrospective multicenter 901 archival samples obtained patients with 31-GEP predictions 5-year (MSS)...