A5013127374- Cardiomyopathy and Myosin Studies
- RNA Research and Splicing
- Muscle Physiology and Disorders
- Biotin and Related Studies
- Peptidase Inhibition and Analysis
- Radiation Effects in Electronics
- Kruppel-like factors research
- Protease and Inhibitor Mechanisms
- Advanced biosensing and bioanalysis techniques
- Congenital heart defects research
- Wnt/β-catenin signaling in development and cancer
- Influenza Virus Research Studies
- Cell Adhesion Molecules Research
- 3D Printing in Biomedical Research
- Viral Infections and Immunology Research
- Avian ecology and behavior
- MicroRNA in disease regulation
- RNA modifications and cancer
- Cancer-related gene regulation
- Extracellular vesicles in disease
- COVID-19 Clinical Research Studies
- Circular RNAs in diseases
- RNA and protein synthesis mechanisms
- Semiconductor materials and devices
- SARS-CoV-2 and COVID-19 Research
Yale University
2024
University of Connecticut
2018-2024
Cardiovascular Research Center
2024
UConn Health
2018-2021
Jackson Laboratory
2018-2021
University of Colorado Denver
2016
Fred Hutch Cancer Center
2014
Toronto Zoo
2010
Exosomes have been proposed as vehicles for microRNA (miRNA) -based intercellular communication and a source of miRNA biomarkers in bodily fluids. Although exosome preparations contain miRNAs, quantitative analysis their abundance stoichiometry is lacking. In the course studying cancer-associated extracellular miRNAs patient blood samples, we found that fractions contained small minority content plasma. This low yield prompted us to perform more assessment relationship between exosomes using...
Highlights•We engineered four iPSC models of HCM with MYH7 and MYBPC3 mutations CRISPR•HCM result in hypercontractility 3D cardiac microtissues•Hypercontractility was independent changes calcium handling•HCM cardiomyocytes exhibit oxidative stress p53-dependent cytotoxicity stressSummaryThick-filament sarcomere are a common cause hypertrophic cardiomyopathy (HCM), disorder heart muscle thickening associated sudden death failure, unclear mechanisms. We isogenic induced pluripotent stem cell...
The human long noncoding RNA (lncRNA) HOTAIR acts in trans to recruit the Polycomb repressive complex 2 (PRC2) HOXD gene cluster and promote silencing during development. In breast cancers, overexpression of increases metastatic potential via repression many additional genes. It has remained unclear what factors determine HOTAIR-dependent PRC2 activity at specific genomic loci, particularly when high levels result aberrant silencing. To identify proteins that contribute action HOTAIR, we...
Actinins are strain-sensing actin cross-linkers that ubiquitously expressed and harbor mutations in human diseases. We utilize CRISPR, pluripotent stem cells, BioID to study actinin interactomes cardiomyocytes. identify 324 proximity partners, including those dependent on sarcomere assembly. confirm 19 known interactors a network of RNA-binding proteins, with RNA localization functions. In vivo biochemical interaction studies support IGF2BP2 localizes electron transport chain transcripts...
Human cardiac regeneration is limited by low cardiomyocyte replicative rates and progressive polyploidization unclear mechanisms. To study this process, we engineer a human model to track replication using fluorescently tagged cyclin B1 troponin T. Using time-lapse imaging, in vitro patterns recapitulate the mononuclear arrest observed vivo. Single-cell transcriptomics chromatin state analyses reveal that preceded sarcomere assembly, enhanced oxidative metabolism, DNA damage response, p53...
Integrins are transmembrane receptors that, as critical participants in a vast range of pathological processes, potential therapeutic targets. However, only few cases has the promise been realized by drug approval. In this review, we briefly review basic integrin biology and participation disease, challenges development safe, effective integrin-targeted therapies, recent advances that may lead to progress.
Abstract Rationale Actinins are actin cross-linkers that ubiquitously expressed and harbor mutations in heritable diseases. The predominant cardiac actinin is encoded by ACTN2 , which a core structural component of the sarcomere Z-disk. required for function through complex interactions with proteins involved assembly, cell signaling transcriptional regulation. However, there remain critical gaps our knowledge complete dynamic interactome, could reveal new insights into biology. Objective We...
Thick filament sarcomere mutations are the most common cause of hypertrophic cardiomyopathy (HCM), a disorder heart muscle thickening associated with sudden cardiac death and failure, unclear mechanisms. We engineered an isogenic panel four human HCM induced pluripotent stem cell (iPSc) models using CRISPR/Cas9, studied iPSc-derived cardiomyocytes (iCMs) in 3-dimensional microtissue (CMT) assays that resemble vivo architecture biomechanics. result hypercontractility association prolonged...
Abstract Transmembrane CD13 assembles protein complexes at the plasma membrane to enable diverse cellular processes such as cell-cell adhesion, focal adhesion turnover, endocytosis and recycling of cell surface proteins. In this study, we demonstrate a novel CD13-dependent assembly platform that regulates phosphoinositide (PI) signal transduction during formation Tunneling Nanotubes (TNTs). TNTs are actin-based, membrane-delimited bridges facilitate intercellular communication by connecting...
Abstract Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide 1 . Laminar shear stress (LSS) from blood flow in straight regions arteries protects against ASCVD by upregulating Klf2/4 anti-inflammatory program endothelial cells (ECs) 2–8 Conversely, disturbed (DSS) at curves or branches predisposes these to plaque formation 9,10 We previously reported a whole genome CRISPR knockout screen 11 that identified novel inducers Klf2/4. Here we report...
During spring and fall migrations, birds migrating during the night are attracted by city lights often collide with Toronto high–rise buildings. Birds also crash into windows day as reflections create an illusion of open sky. Wildlife Centre (TWC) works Fatal Light Awareness Program (FLAP) to assess treat that have been injured. In peak flight times 20 to100 can arrive at centre daily. The arrival so many be a daunting task if one is unprepared. Discussion focuses on how deal these...
The cardiac sarcomere is a multiprotein complex that generates pulsatile contractile force, enabling the heart to circulate vital nutrients, but its molecular components and dynamic interactions are incompletely understood. Cardiac alpha-actinin-2 (encoded by ACTN2 ; referred as actinin) functions structural backbone of Z-disc prone mutations result in human failure. We hypothesize through identifying actinin PPIs at Z-disc, we can identify new gain insights into failure pathogenesis. Until...
Human cardiac regeneration is limited by low cardiomyocyte replicative rates and progressive polyploidization unclear mechanisms. To study this process, we engineered a human model to track replication using fluorescently tagged cyclin B1 troponin T. Using time-lapse imaging, in vitro patterns recapitulated the mononuclear arrest observed vivo. Single-cell transcriptomics epigenetic analyses revealed that was preceded sarcomere formation, enhanced oxidative metabolism, DNA damage response,...