A5088962044- Microtubule and mitosis dynamics
- Cardiomyopathy and Myosin Studies
- Congenital heart defects research
- Pulmonary Hypertension Research and Treatments
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Genetics, Aging, and Longevity in Model Organisms
- Amyotrophic Lateral Sclerosis Research
- Cardiac Structural Anomalies and Repair
- Cardiac Fibrosis and Remodeling
- Mitochondrial Function and Pathology
- Mechanical Circulatory Support Devices
- Receptor Mechanisms and Signaling
- Nuclear Structure and Function
- Congenital Heart Disease Studies
- CRISPR and Genetic Engineering
- Neurological diseases and metabolism
- Photosynthetic Processes and Mechanisms
- Computational Drug Discovery Methods
- Adipose Tissue and Metabolism
- Parkinson's Disease Mechanisms and Treatments
- PI3K/AKT/mTOR signaling in cancer
- Fuel Cells and Related Materials
- Cellular transport and secretion
- Tissue Engineering and Regenerative Medicine
University of Pennsylvania
2012-2025
California University of Pennsylvania
2025
Children's Hospital of Philadelphia
2022
University of Washington
2015-2019
Seattle University
2019
Abstract Hypertension, exercise, and pregnancy are common triggers of cardiac remodeling, which occurs primarily through the hypertrophy individual cardiomyocytes. During hypertrophy, stress-induced signal transduction increases cardiomyocyte transcription translation, promotes addition new contractile units poorly understood mechanisms. The microtubule network is also implicated in but via an unknown role. Here, we show that microtubules indispensable for growth spatiotemporal control...
Abstract Background No therapies exist to reverse right ventricular failure (RVF), and the molecular mechanisms that drive RVF remain poorly studied. We recently reported developmentally restricted noncanonical WNT receptor ROR2 is upregulated in human proportion severity of disease. Here we test mechanistic role pathogenesis. Methods was overexpressed or knocked down neonatal rat myocytes (NRVMs). ROR2-modified NRVMs were characterized using confocal microscopy, RNAseq, proteomics,...
Cardiac hypertrophy allows post-mitotic cardiomyocytes to meet increased hemodynamic demands but can predispose the heart adverse clinical outcomes. Despite its central role in cardiac adaptation, translational control mechanisms that drive are poorly understood. In this study, we elucidate relative contributions of various operant during homeostasis and hypertrophic growth. A combination immunofluorescence single myocyte protein synthesis assays were used dissect single-cardiomyocyte under...
Significance During cell division, multisubunit kinetochores partition chromosomes while maintaining a grip on dynamic microtubules under tension. Previous work in Caenorhabditis elegans showed that the central kinetochore component, Mis12/MIND (Mtw1, Nsl1, Nnf1, Dsn1) complex, increases microtubule binding of outer complexes, but mechanism for this enhancement remains unknown. Here, we identify new contacts between MIND and Ndc80 (Ndc80, Nuf2, Spc24, Spc25) complex are essential interaction...
Regulation of the outer kinetochore complex Ndc80 is essential to ensure correct kinetochore-microtubule attachments during mitosis. Here, we present a novel mechanism regulation that intrinsic its structure; tight bending inhibits microtubule binding. Using single molecule Förster resonance energy transfer (FRET), show Saccharomyces cerevisiae can fluctuate between straight and bent forms, binding microtubules selects for straightened forms. The loop region enables conformation, as deletion...
Background: No therapies exist to treat right ventricular failure (RVF), in part because RVF molecular drivers have been incompletely studied. We recently identified that the developmentally restricted noncanonical WNT receptor ROR2 is re-expressed a severity-dependent manner human RVF. Here we test mice if, and how, re-expression of Ror2 causes Methods/Results: find neonatal rat myocytes (NRVMs) overexpression (Ror2 OE ) both activates protein translation reduces Hspa1a/b mRNA Hsp70...
No therapies exist to reverse right ventricular failure (RVF), in part because RVF molecular drivers have been incompletely characterized. We recently identified RVF-severity dependent re-expression of the developmental noncanonical WNT receptor Ror2 dilated and ischemic cardiomyopathy RV. now demonstrate that plays a novel role regulating cardiomyocyte proteostasis (Figure). NRVMs with overexpression (Ror2 OE ) are smaller, rounder fragmented sarcomeres, loss intercalated disc proteins,...
Introduction: The post-mitotic cardiomyocyte (CM) must maintain proteostasis while also preserving the ability to remodel, particularly during times of cardiac growth. How CM couples transcription and translation in space time for normal maintenance cell is understudied, thus it unclear how these programs are co-opted enable hypertrophy. Our lab’s previous work has indicated necessity microtubules (MTs) kinesin-1 proper localization transcripts, growth CM, yet molecular mechanisms that...
Introduction: We recently identified the fetal noncanonical WNT receptor ROR2 as being re-expressed in human right ventricular failure (RVF), but myocardial role of remains poorly described. Hypothesis: assessed if expression influences cardiomyocyte structure or contributes to RVF pathogenesis. Methods: gain- and loss-of-function (ROR2 GOF LOF ) NRVMs were generated using adenoviral-delivered cDNA shRNA cultured on nanopatterned substrates. NRVM was by confocal microscopy (minimum n=3...