A5101957756- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- Muscle Physiology and Disorders
- Cardiovascular Function and Risk Factors
- Congenital heart defects research
- Prenatal Screening and Diagnostics
- Pregnancy and preeclampsia studies
- Cardiac electrophysiology and arrhythmias
- RNA Research and Splicing
- Cardiac Fibrosis and Remodeling
- RNA and protein synthesis mechanisms
- Renal and related cancers
- PARP inhibition in cancer therapy
- Diabetes Treatment and Management
- Viral Infections and Immunology Research
- Congenital Diaphragmatic Hernia Studies
- Studies on Chitinases and Chitosanases
- Signaling Pathways in Disease
- Nuclear Structure and Function
- Neurogenetic and Muscular Disorders Research
- Tissue Engineering and Regenerative Medicine
- Machine Learning in Materials Science
- Computational Drug Discovery Methods
University of Cincinnati
2019-2025
University of Cincinnati Medical Center
2020-2024
Amgen (United States)
2022-2024
Duke University
2024
University of North Texas
2015-2023
Sabin Vaccine Institute
2020
Significance Cardiac myosin binding protein-C (cMyBP-C) is a sarcomeric protein closely linked to cardiac contractility. Importantly, although the phosphorylation status of cMyBP-C regulates force and rate contraction, exact molecular mechanism(s) remain(s) unclear. Previously, loss of, or mutations in, resulted in inhibited super-relaxed state (SRX) myosin, which explains hypercontractile phenotype. Thus, we asked if would increase contractile function by release heads from SRX more...
Abstract The outer surface of chorionic villi in the human placenta consists a single multinucleated cell called syncytiotrophoblast (STB). unique cellular ultrastructure STB presents challenges deciphering its gene expression signature at single-cell level, as contains billions nuclei cell. There are many gaps understanding molecular mechanisms and developmental trajectories involved formation differentiation. To identify underlying control STB, we performed comparative nucleus (SN) (SC)...
Dilated cardiomyopathy (DCM) due to genetic disorders results in decreased myocardial contractility, leading high morbidity and mortality rates. There are several therapeutic challenges treating DCM, including poor understanding of the underlying mechanism impaired contractility difficulty developing targeted therapies reverse mutation-specific pathologies. In this report, we focused on K210del, a DCM-causing mutation, 3-nucleotide deletion sarcomeric troponin T (TnnT), resulting loss...
Type 2 diabetes mellitus (T2DM) is a metabolic disease and comorbidity associated with several conditions, including cardiac dysfunction leading to heart failure preserved ejection fraction (HFpEF), in turn resulting T2DM-induced cardiomyopathy (T2DM-CM). However, the molecular mechanisms underlying development of T2DM-CM are poorly understood. It hypothesized that alterations myopathic genes induced by promote HFpEF, whereas myosin inhibitors can rescue resultant T2DM-mediated...
BACKGROUND: Recent interest in understanding cardiomyocyte cell cycle has been driven by potential therapeutic applications cardiomyopathy. However, despite recent advances, mitosis remains a poorly understood process. For example, it is unclear how sarcomeres are disassembled during to allow the abscission of daughter cardiomyocytes. METHODS: Here, we use proteomics screen identify adducin, an actin capping protein previously not studied cardiomyocytes, as regulator sarcomere disassembly....
Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular disorder primarily caused by mutations in the β-myosin heavy-chain gene. The proximal subfragment 2 region (S2), 126 amino acids of myosin, binds with C0-C2 cardiac myosin-binding protein-C to regulate muscle contractility a manner dependent on PKA-mediated phosphorylation. However, it unknown if HCM-associated within S2 dysregulate actomyosin dynamics disrupting its interaction C0-C2, ultimately leading HCM. Herein, we study...
Abstract BACKGROUND MYBPC3 , encoding cardiac myosin binding protein-C (cMyBP-C), is the most mutated gene known to cause hypertrophic cardiomyopathy (HCM). However, since little about underlying etiology, additional in vitro studies are crucial defining molecular mechanisms. Accordingly, this study aimed investigate mechanisms pathogenesis of HCM associated with a polymorphic variant (D389V) by using human-induced pluripotent stem cell (hiPSC)-derived organoids (hCOs). METHODS The...
Allostery, a fundamental structural mechanism where ligand binding at protein site affects function another site, plays crucial role in key drug-target proteins like GPCRs. Unfortunately, existing methods for predicting allosteric sites have limited performance-- they are particularly constrained by scarce ground-truth experimental data. We introduce Allo-Allo, data-efficient, sequence-based method that predicts leveraging language models (PLMs). Honing on ESM-2 attention heads capture...
The outer surface of chorionic villi in the human placenta consists a single multinucleated cell called syncytiotrophoblast (STB). unique cellular ultrastructure STB presents challenges deciphering its gene expression signature at single-cell level, as contains billions nuclei cell. There are many gaps understanding molecular mechanisms and developmental trajectories involved formation differentiation. To identify underlying control STB, we performed comparative nucleus (SN) (SC) RNA...
The outer surface of chorionic villi in the human placenta consists a single multinucleated cell called syncytiotrophoblast (STB). unique cellular ultrastructure STB presents challenges deciphering its gene expression signature at single-cell level, as contains billions nuclei cell. There are many gaps understanding molecular mechanisms and developmental trajectories involved formation differentiation. To identify underlying control STB, we performed comparative nucleus (SN) (SC) RNA...
, encoding cardiac myosin binding protein-C (cMyBP-C), is the most mutated gene known to cause hypertrophic cardiomyopathy (HCM). However, since little about underlying etiology, additional in vitro studies are crucial defining molecular mechanisms. Accordingly, this study aimed investigate mechanisms pathogenesis of HCM associated with a polymorphic variant (D389V)
Modulation of sarcomere contractility represents a new therapeutic opportunity for the treatment heart failure by directly targeting thick and thin filament proteins to increase cardiac muscle contraction. This study compared effect 2 small molecules (M T) that selectively alter myosin (M) or troponin (T) activity on overall mechanics. revealed key differences related mechanism utilized M T contractile force generation suggests different within may result in differentiating profiles.
Data presented in this article relates to the research entitled "Whole length myosin binding protein C stabilizes subfragment-2 (S2) flexibility as measured by gravitational force spectroscopy." (Singh et al., 2018) [1]. The data exhibits purified skeletal (MyBPC) from rabbit back muscle was of slow type confirmed chromatography and unphosphorylated state based on its isoelectric point (pI) chromatofocussing. competitive enzyme linked immunosorbent assay (cELISA) displayed site specificity...
Abstract During heart failure, gene and protein expression profiles undergo extensive compensatory pathological remodeling. We previously observed that fast skeletal myosin binding protein-C (fMyBP-C) is upregulated in diseased mouse hearts. While fMyBP-C shares significant homology with its cardiac paralog, (cMyBP-C), there are key differences may affect function. However, it unknown if the of a or response. aim to elucidate consequence either increased knockout expression. To determine...
Introduction: Recent interest in understanding the cardiomyocyte cell cycle has been driven by potential therapeutic applications cardiomyopathy. Despite advancements, intricacies of mitosis, especially breakdown sarcomeres to enable daughter cardiomyocytes' division, remain largely unexplored. Hypothesis: This study investigates role Adducin disassembly during hypothesizing that serves as a crucial regulator this process. Goals: Our objective is elucidate function sarcomere mitosis...
Background: Cardiac muscle contraction and relaxation are regulated by the interaction between myosin neck region (S2) cardiac binding protein-C (cMyBP-C). Clinically, several mutations in S2 region, affecting its with cMyBP-C, have been linked to hypertrophic cardiomyopathy (HCM). However, molecular mechanism which affect function is unknown. The of cMyBP-C whether facilitating this using a small peptide can efficiently improve contractility remains unclear. Objectives: To determine...
Abstract Recent interest in understanding cardiomyocyte cell-cycle has been driven by potential therapeutic applications cardiomyopathy. However, despite recent advances, mitosis remains a poorly understood process. For example, it is unclear how sarcomeres are disassembled during to allow abscission of daughter cardiomyocytes. Here we identify adducin as regulator sarcomere disassembly mammalian mitosis. α/γ-adducins selectively expressed neonatal mitotic cardiomyocytes, and their levels...
Rationale: Affecting 1 in 300 individuals, hypertrophic cardiomyopathy (HCM) is a genetic heart disease characterized by left ventricular hypertrophy, myocardial disarray, and sudden cardiac death. Often, HCM associated with hypercontractility. The subfragment-2 (S2) of beta-myosin heavy chain contains cluster missense deletion mutations severe HCM. Interestingly, myosin S2 interacts the C0-C2 region binding protein C (cMyBP-C) phosphorylation-dependent manner to regulate sarcomere...
A 25-base pair (25bp) intronic deletion in the