A5027073380- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- Cardiovascular Function and Risk Factors
- Muscle Physiology and Disorders
- Viral Infections and Immunology Research
- Sports injuries and prevention
- Cardiac electrophysiology and arrhythmias
- Cardiovascular and exercise physiology
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Force Microscopy Techniques and Applications
- Advanced MRI Techniques and Applications
- Signaling Pathways in Disease
- Genetics and Physical Performance
- Birth, Development, and Health
- Neurogenetic and Muscular Disorders Research
- Acute Myocardial Infarction Research
- Cardiac Fibrosis and Remodeling
- Peptidase Inhibition and Analysis
- Cardiac pacing and defibrillation studies
- Hemiptera Insect Studies
- RNA modifications and cancer
- Exercise and Physiological Responses
- Mercury impact and mitigation studies
- Advanced Proteomics Techniques and Applications
Florida State University
2016-2024
Tallahassee Orthopedic Clinic
2021
Universidade Federal do Rio de Janeiro
2014
National Institute of Science and Technology for Structural Biology and Bioimaging
2014
Significance Heartbeats rely on cyclical interactions between myosin thick and actin thin filaments orchestrated by rising falling Ca 2+ . During systole, binds to the filament allows its interaction with produce force required for contraction. The structure of at physiological levels is unknown, which limits our understanding regulation Here, we directly observe structural states along individual systolic show that activated stochastically short-range cooperativity evident only one strand...
Nuclear factor kappa-B (NFκB) is activated in arrhythmogenic cardiomyopathy (ACM) patient-derived iPSC-cardiac myocytes under basal conditions and inhibition of NFκB signaling prevents disease Dsg2mut/mut mice, a robust mouse model ACM. Here, we used genetic approaches single cell RNA sequencing to define the contributions immune cardiac macrophages natural progression ACM using mice. We found that drives myocardial injury, contractile dysfunction, arrhythmias mobilizes expressing C-C motif...
Fast skeletal myosin-binding protein-C (fMyBP-C) is one of three MyBP-C paralogs and predominantly expressed in fast muscle. Mutations the gene that encodes fMyBP-C,
Missense variant Ile79Asn in human cardiac troponin T (cTnT-I79N) has been associated with hypertrophic cardiomyopathy and sudden arrest juveniles. cTnT-I79N is located the cTnT N-terminal (TnT1) loop region known for its pathological prognostic relevance. A recent structural study revealed that I79 part of a hydrophobic interface between TnT1 actin, which stabilizes relaxed (OFF) state thin filament. Given importance understanding role Ca 2+ regulation filament along underlying mechanisms...
Myocyte disarray is a hallmark of many cardiac disorders. However, the relationship between alterations in orientation individual myofibrils and myofilaments to disease progression has been largely underexplored. This oversight predominantly because paucity methods for objective quantitative analysis. Here, we introduce novel, less-biased approach quantify myofibrillar myofilament muscle under near-physiological conditions demonstrate its superiority as compared with conventional...
Abstract Aims Platelet activation and endothelial dysfunction contribute to adverse outcomes in patients with acute coronary syndromes (ACS). The goals of this study were assess the impact proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition on markers platelet ACS interaction among PCSK9, platelets, cells (ECs) left internal mammary artery (LIMA) vascular endothelium using specimens obtained during bypass surgery (CABG). Methods Results Acute enrolled Evolocumab trials...
Phosphorylation and acetylation of sarcomeric proteins are important for fine-tuning myocardial contractility. Here, we used bottom-up proteomics label-free quantification to identify novel post-translational modifications (PTMs) on β-myosin heavy chain (β-MHC) in normal failing human heart tissues. We report six acetylated lysines two phosphorylated residues: K34-Ac, K58-Ac, S210-P, K213-Ac, T215-P, K429-Ac, K951-Ac, K1195-Ac. K951-Ac was significantly reduced both ischemic nonischemic...
Aberrant regulation of myocardial force production represents an early biomechanical defect associated with sarcomeric cardiomyopathies, but the molecular mechanisms remain poorly defined. Here, we evaluated pathogenicity a previously unreported gene variant identified in pediatric patient sporadic dilated cardiomyopathy, and determined mechanism. Trio whole-exome sequencing revealed de novo missense TNNC1 that encodes p.I4M substitution N-terminal helix cardiac troponin C (cTnC)....
Familial dilated cardiomyopathy (DCM), clinically characterized by enlargement and dysfunction of one or both ventricles the heart, can be caused variants in sarcomeric genes, including TNNC1 (encoding cardiac troponin C, cTnC). Here, we report case two siblings with severe, early-onset DCM who were found to have compound heterozygous TNNC1: p.Asp145Glu (D145E) p.Asp132Asn (D132N), which inherited from parents. We began our investigation CRISPR/Cas9 knockout Xenopus tropicalis, resulted a...
Mutations in TNNC1—the gene encoding cardiac troponin C (cTnC)—that have been associated with hypertrophic cardiomyopathy (HCM) and dysfunction may also affect Ca2+-regulation function of slow skeletal muscle since the same is expressed both muscle. Therefore, we reconstituted rabbit soleus fibers bovine masseter myofibrils mutant cTnCs (A8V, C84Y, E134D D145E) HCM to investigate their effects on contractile force ATPase rates, respectively. Previously, showed that these cTnC mutants, except...
Inhibition of nuclear factor kappa-B (NFκB) signaling prevents disease in Dsg2 mut/mut mice, a model arrhythmogenic cardiomyopathy (ACM). Moreover, NFκB is activated ACM patient-derived iPSC-cardiac myocytes under basal conditions vitro . Here, we used genetic approaches and sequencing studies to define the relative pathogenic roles immune cardiac vs. inflammatory cells mice. We found that drives myocardial injury, contractile dysfunction, arrhythmias It does this by mobilizing expressing...
Striated muscle is activated by myosin- and actin-linked processes, with the latter being regulated through changes in position of tropomyosin relative to actin surface. The C-terminal region cardiac troponin T (TnT), a tropomyosin-associated protein, required for full TnT inactivation at low Ca2+ limiting its activation saturating Here, we investigated whether basic residues this are involved these activities, C terminus undergoes Ca2+-dependent conformational changes, affect contraction....
Considerable effort has gone into investigating mechanisms that underlie the developmental transition in which mammalian cardiomyocytes (CMs) switch from being able to proliferate during development, essentially having lost ability at maturity. This problem is interesting not only for scientific curiosity, but also its clinical relevance because controlling of mature CMs replicate would provide a much-needed approach restoring cardiac function damaged hearts. In this review, we focus on...