A5011074040- Nuclear Structure and Function
- RNA Research and Splicing
- Skin and Cellular Biology Research
- Genetic and Kidney Cyst Diseases
- Photosynthetic Processes and Mechanisms
- Advanced Electron Microscopy Techniques and Applications
- Genomics and Chromatin Dynamics
- Advanced Fluorescence Microscopy Techniques
- Biotin and Related Studies
- Force Microscopy Techniques and Applications
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- RNA and protein synthesis mechanisms
- Cardiomyopathy and Myosin Studies
- Viral Infections and Immunology Research
- Neonatal Respiratory Health Research
- Renal and related cancers
- Protist diversity and phylogeny
- Cardiovascular Effects of Exercise
Agency for Science, Technology and Research
2017-2023
Institute of Medical Biology
2017-2022
Stanford University
2011-2015
The nucleus is the main microtubule-organizing center (MTOC) in muscle cells due to accumulation of centrosomal proteins and microtubule (MT) nucleation activity at nuclear envelope (NE) [1Bugnard E. Zaal K.J.M. Ralston Reorganization during differentiation.Cell Motil. Cytoskeleton. 2005; 60: 1-13Crossref PubMed Scopus (113) Google Scholar, 2Fant X. Srsen V. Espigat-Georger A. Merdes Nuclei non-muscle bind centrosome upon fusion with differentiating myoblasts.PLoS ONE. 2009; 4: e8303Crossref...
Mutations in the LaminA gene are a common cause of monogenic dilated cardiomyopathy. Here we show that mice with cardiomyocyte-specific Lmna deletion develop cardiac failure and die within 3-4 weeks after inducing mutation. When same mutations induced genetically deficient LINC complex protein SUN1, life is extended to more than one year. Disruption SUN1's function also accomplished by transducing expressing dominant-negative SUN1 miniprotein cardiomyocytes, using cardiotrophic Adeno...
Defects in centrosome and cilium function are associated with phenotypically related syndromes called ciliopathies. Cby1, the mammalian orthologue of Drosophila Chibby protein, localizes to mature centrioles, is important for ciliogenesis multiciliated airway epithelia mice, antagonizes canonical Wnt signaling via direct regulation β-catenin. We report that deletion mouse Cby1 gene results cystic kidneys, a phenotype common ciliopathies, facilitates formation primary cilia ciliary...
Mutations in LMNA, the gene encoding A-type lamins, cause laminopathies-diseases of striated muscle and other tissues. The aetiology laminopathies has been attributed to perturbation chromatin organization or structural weakening nuclear envelope (NE) such that nucleus becomes more prone mechanical damage. latter model requires a conduit for force transmission nucleus. NE-associated Linker Nucleoskeleton Cytoskeleton (LINC) complexes are one pathway. Using clustered regularly interspaced...
Abstract Background Dilated cardiomyopathy (DCM) is a severe, non-ischemic heart disease which ultimately results in failure (HF). Decades of research on DCM have revealed diverse aetiologies. Among them, familial the major form DCM, with pathogenic variants LMNA being second most common autosomal dominant DCM. multifactorial and complex no specific treatment thus far. Many studies demonstrated that perturbing candidates related to various dysregulated pathways ameliorate However, it unknown...
Far-field super-resolution microscopy is a rapidly emerging method that opening up opportunities for biological imaging beyond the optical diffraction limit. We have implemented Stimulated Emission Depletion (STED) microscope to image single dye, cell, and tissue samples with 50-80 nm resolution. First, we compare STED performance molecules of several common dyes report novel dye. Then apply planar cell polarity protein complexes in intact fixed
Durotaxis is a phenomenon in which cells migrate toward substrates of increasing stiffness. However, how assimilate substrate stiffness as directional cue remains poorly understood. In this study, we experimentally show that mouse embryonic fibroblasts can discriminate between different stiffnesses and develop higher traction forces at regions the cell adhering to stiffer pillars. way, generate force imbalance adhesion sites. It drives durotaxis by providing directionality for migration....
Mutations in the LMNA gene are second most common cause of genetic dilated cardiomyopathies (DCMs) with a prevalence ~1/12500. Adeno-associated virus (AAV) therapies promising treatment modality for disease. However, autosomal dominant, gain-of-function mutations underlying DCM preclude standard replacement approaches. To understand DCM, we previously generated mouse model that exhibits reduced ejection fraction, dilation ventricular inner dimensions and increased cardiac fibrosis, surviving...
Mutations in the LMNA gene, encoding lamin A/C, are one of most frequent genetic causes dilated cardiomyopathy. While gene therapy using adeno-associated virus (AAV) vectors show promise for treatment monogenic diseases, DCM mutations tend to be autosomal dominant and gain-of-function, precluding typical replacement approaches. Lamin A/C forms a filamentous network, nuclear lamina, underlying envelope that is thought function maintaining structural integrity nucleus by resisting cytoskeletal...