A5076680220- Microtubule and mitosis dynamics
- Congenital heart defects research
- Genomics and Chromatin Dynamics
- Neurofibromatosis and Schwannoma Cases
- Congenital Heart Disease Studies
- Ubiquitin and proteasome pathways
- Cancer Mechanisms and Therapy
- Chromosomal and Genetic Variations
- Hippo pathway signaling and YAP/TAZ
- Cellular transport and secretion
- Mechanisms of cancer metastasis
- CRISPR and Genetic Engineering
- Cellular Mechanics and Interactions
- Photosynthetic Processes and Mechanisms
- DNA Repair Mechanisms
- Renal and related cancers
- RNA Research and Splicing
- Congenital Diaphragmatic Hernia Studies
- Cancer-related Molecular Pathways
- Signaling Pathways in Disease
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
- Axon Guidance and Neuronal Signaling
- Phagocytosis and Immune Regulation
- Renal Diseases and Glomerulopathies
Harvard University
2014-2025
Morehouse School of Medicine
2007-2019
University of Science and Technology of China
2011-2019
Beijing University of Chinese Medicine
2011-2019
Center for Excellence in Molecular Cell Science
2013-2019
Brigham and Women's Hospital
2016
Imaging Center
2012-2015
UPMC Hillman Cancer Center
2011
Air Force Medical University
2011
Xijing Hospital
2011
A mouse model reveals how seven atrial fibrillation–related risk genes form a network to control heartbeat.
In eukaryotes, microtubules are essential for cellular plasticity and dynamics. Here we show that P300/CBP-associated factor (PCAF), a kinetochore-associated acetyltransferase, acts as negative modulator of microtubule stability through acetylation EB1, protein controls the plus ends microtubules. PCAF acetylates EB1 on K220 disrupts hydrophobic cavity dimerized C terminus, which was previously reported to interact with plus-end tracking proteins (TIPs) containing SxIP motif. As determined...
Abstract Human induced pluripotent stem cells (hiPSCs) can be used to mass produce surrogates of human tissues, enabling new advances in drug screening, disease modeling, and cell therapy. Recent developments clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing technology use homology‐directed repair (HDR) efficiently generate custom hiPSC lines harboring a variety genomic insertions deletions. Thus, hiPSCs that encode an endogenous protein fused fluorescent...
Damaging GATA6 variants cause cardiac outflow tract defects, sometimes with pancreatic and diaphragmic malformations. To define molecular mechanisms for these diverse developmental we studied transcriptional epigenetic responses to loss of function (LoF) missense during cardiomyocyte differentiation isogenic human induced pluripotent stem cells. We show that is a pioneer factor in development, regulating SMYD1 activates HAND2, KDR HAND2 orchestrates formation. LoF perturbed genes also...
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Chromosome segregation in mitosis is orchestrated by dynamic interaction between spindle microtubules and the kinetochore, a multiprotein complex assembled onto centromeric DNA of chromosome. Here, we show that Homo sapiens (Hs) NUF2 required for stable kinetochore localization centromere-associated protein E (CENP-E) HeLa cells. HsNUF2 specifies association CENP-E interacting with its C-terminal domain. The region binding to was mapped domain glutathione S-transferase pulldown yeast...
Chromosome segregation in mitosis is orchestrated by dynamic interaction between spindle microtubules and the kinetochore. Septin (SEPT) belongs to a conserved family of polymerizing GTPases localized metaphase during mitosis. Previous study showed that SEPT2 depletion results chromosome mis-segregation correlated with loss centromere-associated protein E (CENP-E) from kinetochores congressing chromosomes (1). However, it has remained elusive as whether CENP-E physically interacts SEPT how...
Chromosome movements in mitosis are orchestrated by dynamic interactions between spindle microtubules and the kinetochore, a multiprotein complex assembled onto centromeric DNA of chromosome. Here we show that phosphorylation human HsMis13 Aurora B kinase is required for functional kinetochore assembly HeLa cells. interacts with vitro vivo. cognate substrate B, sites were mapped to Ser-100 Ser-109. Suppression either small interfering RNA or chemical inhibitors abrogates localization but not...
Abstract During progression of hepatocellular carcinoma, multiple genetic and epigenetic alterations act to posttranslationally modulate the function proteins that promote cancer invasion metastasis. To define such abnormalities contribute liver metastasis, we carried out a proteomic comparison primary carcinoma samples intravascular thrombi from same patient. Mass spectrometric analyses revealed series acidic phospho-isotypes associated with samples. In particular, found Thr567...
Background SMAD2 is a coregulator that binds variety of transcription factors in human development. Heterozygous loss‐of‐function and missense variants are identified patients with congenital heart disease (CHD) or arterial aneurysms. Mechanisms cause distinct cardiovascular phenotypes remain unknown. We aimed to define transcriptional epigenetic effects their role CHD. also assessed the function uncertain significance. Methods Results Rare (minor allele frequency ≤10 −5 ) were exome...
Helicobacter pylori persistently colonize the human stomach and have been linked to atrophic gastritis gastric carcinoma. Although it is well known that H. infection can result in hypochlorhydria, molecular mechanisms underlying this phenomenon remain poorly understood. Here we show VacA permeabilizes apical membrane of parietal cells induces hypochlorhydria. The functional consequences on cell physiology were studied using freshly isolated rabbit glands cultured cells. Secretory activity...
Mitosis is an orchestration of dynamic interaction between chromosomes and spindle microtubules by which genomic materials are equally distributed into two daughter cells. Previous studies showed that CENP-U a constitutive centromere component essential for proper chromosome segregation. However, the precise molecular mechanism has remained elusive. Here, we identified as novel interacting partner Hec1, evolutionarily conserved kinetochore core plasticity. Suppression shRNA resulted in...
Mitotic chromosome segregation is orchestrated by the dynamic interaction of spindle microtubules with kinetochore. Although previous studies show that mitotic kinesin CENP-E forms a link between attachment microtubule to kinetochore and checkpoint signaling cascade, molecular mechanism underlying kinetochore-microtubule interactions in mammalian cells remains elusive. Here, we identify novel SKAP functions synergistically governing interactions. binds C-terminal tail vitro essential for an...
Entosis, a cell-in-cell process, has been implicated in the formation of aneuploidy associated with an aberrant cell division control. Microtubule plus-end-tracking protein TIP150 facilitates loading MCAK onto microtubule plus ends and orchestrates plus-end dynamics during division. Here we show that cooperates to govern entosis via regulatory circuitry involves Aurora A-mediated phosphorylation MCAK. Our biochemical analyses forms intra-molecular association, which is essential for binding....
The ezrin-radixin-moesin proteins provide a regulated linkage between membrane and the cortical cytoskeleton also participate in signal transduction pathways. Ezrin is localized to apical of parietal cells couples protein kinase A activation cascade HCl secretion. Our recent proteomic study revealed complex ezrin-ACAP4-ARF6 essential for volatile remodeling (Fang, Z., Miao, Y., Ding, X., Deng, H., Liu, S., Wang, F., Zhou, R., Watson, C., Fu, Hu, Q., Lillard, J. W., Jr., Powell, M., Chen,...
Error-free cell division depends on the accurate assembly of spindle midzone from dynamic microtubules to ensure chromatid segregation during metaphase-anaphase transition. However, mechanism underlying key transition mitotic central before anaphase onset remains elusive. Given prevalence chromosome instability phenotype in gastric tumorigenesis, we developed a strategy model context-dependent using combination light sheet microscope and 3D organoids. Light microscopic image analyses...
Syntaxin and Munc18 are essential for regulated exocytosis in all eukaryotes. It was shown that inhibition of neuronal syntaxin 1 can be overcome by CDK5 phosphorylation, indicating structural change disrupts the syntaxin–Munc18 interaction. Here, we show this phosphorylation promotes assembly Munc18b–syntaxin 3–SNAP25 tripartite complex membrane fusion machinery SNARE. Using siRNAs to screen genes required epithelial secretion, identified requirements Munc18b cAMP‐dependent gastric acid...
Faithful segregation of mitotic chromosomes requires bi-orientation sister chromatids, which relies on the sensing correct attachments between spindle microtubules and kinetochores. Although mechanisms underlying PLK1 activation have been extensively studied, regulatory that couple activity to accurate chromosome are not well understood. In particular, is implicated in stabilizing kinetochore-microtubule attachments, but how kinetochore regulated avoid hyperstabilized...
ABSTRACT Encephalitozoon intestinalis is a microsporidian species that infects the intestinal mucosal epithelium, primarily in immunodeficient individuals. The present study employed undifferentiated and differentiated human colonic carcinoma cell lines to determine if this parasite infected polarized epithelial cells by spore phagocytosis or impalement with deployed polar tube. Apical surface attachment differed between such SW480>HT-29>Caco-2>HCT-8, being greater Caco-2 than...
Ezrin–radixin–moesin protein family provides a regulated link between the cortical actin cytoskeleton and plasma membrane. Phosphorylation of ezrin has been functionally linked to membrane dynamics plasticity. Our recent study demonstrated that phosphorylation conserved T567 residue alters physiology gastric parietal cells. However, molecular mechanism phosphorylation‐induced activation remained elusive. Here we use atomic force microscopy (AFM) probe phosphorylation‐mediated in single...
The digestive function of the stomach depends on acidification gastric lumen. Acid secretion into lumen is triggered by activation PKA cascade, which ultimately results in insertion H,K-ATPases apical plasma membranes parietal cells. A coupling protein ezrin, whose phosphorylation at Ser-66 required for cell activation. However, little known regarding molecular mechanism(s) this signaling pathway operates acid secretion. Here we show that cooperates with MST4 to orchestrate...