A5046152669- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Mitochondrial Function and Pathology
- Advanced Fluorescence Microscopy Techniques
- Liver Disease Diagnosis and Treatment
- Erythrocyte Function and Pathophysiology
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Drug Transport and Resistance Mechanisms
- RNA Research and Splicing
- ATP Synthase and ATPases Research
- Cell Adhesion Molecules Research
- Liver physiology and pathology
- Cancer, Lipids, and Metabolism
- Microtubule and mitosis dynamics
- FOXO transcription factor regulation
- Receptor Mechanisms and Signaling
- Monoclonal and Polyclonal Antibodies Research
- Protein Kinase Regulation and GTPase Signaling
- Photosynthetic Processes and Mechanisms
- Cancer-related gene regulation
- Hippo pathway signaling and YAP/TAZ
- Adipose Tissue and Metabolism
- Cell Image Analysis Techniques
- Pediatric Hepatobiliary Diseases and Treatments
National Institutes of Health
2009-2024
National Cancer Institute
2016-2024
Center for Cancer Research
2021-2024
National Institute of Dental and Craniofacial Research
2012-2019
ORCID
2017
National Heart Lung and Blood Institute
2007-2013
Tel Aviv University
2006-2009
Abstract In the liver, mitochondria are exposed to different concentrations of nutrients due their spatial positioning across periportal and pericentral axis. How sense integrate these signals respond maintain homeostasis is not known. Here, we combine intravital microscopy, proteomics, functional assessment investigate mitochondrial heterogeneity in context liver zonation. We find that morphologically functionally distinct; beta-oxidation elevated regions, while lipid synthesis predominant...
Clathrin‐independent endocytosis (CIE) allows internalization of plasma membrane proteins lacking clathrin‐targeting sequences, such as the major histocompatibility complex class I protein (MHCI), into cells. After internalization, vesicles containing MHCI fuse with transferrin‐containing endosomes generated from clathrin‐dependent endocytosis. In HeLa cells, is subsequently routed to late or recycled back out (PM) in distinctive tubular carriers. Arf6 associated endosomal membranes carrying...
We report a novel mechanism of action ONC201 as mitochondria-targeting drug in cancer cells. was originally identified small molecule that induces transcription TNF-related apoptosis-inducing ligand (TRAIL) and subsequently kills cells by activating TRAIL death receptors. In this study, we examined toxicity on multiple human breast endometrial cell lines. attenuated viability all lines tested. Unexpectedly, not dependent either receptors nor caspases. Time-lapse live imaging revealed...
Bile, the central metabolic product of liver, is transported by bile canaliculi network. The impairment flow in cholestatic liver diseases has urged a demand for insights into its regulation. Here, we developed predictive 3D multi-scale model that simulates fluid dynamic properties successively from subcellular to tissue level. integrates structure canalicular network mouse lobule, as determined high-resolution confocal and serial block-face scanning electron microscopy, with measurements...
Trafficking of H-Ras was examined to determine whether it can enter cells through clathrin-independent endocytosis (CIE). colocalized with the CIE cargo protein, class I major histocompatibility complex, and sequestered in vacuoles that formed upon expression an active mutant Arf6, Q67L. Activation Ras, either epidermal growth factor stimulation or G12V, induced plasma membrane ruffling macropinocytosis, a stimulated form CIE. Live imaging expressing H-RasG12V fluorescent protein chimeras...
Liver kinase B1 (LKB1) and its downstream effector AMP‐activated protein (AMPK) play critical roles in polarity establishment by regulating membrane trafficking energy metabolism. In collagen sandwich‐cultured hepatocytes, loss of LKB1 or AMPK impaired apical ABCB11 (Bsep) bile canalicular formation. the present study, we used liver‐specific (albumin‐Cre) knockout mice (LKB1 −/− ) to investigate role maintenance functional tight junction (TJ) vivo . Transmission electron microscopy...
Little is known about the spatiotemporal coordination of mitochondrial metabolism in multicellular organisms situ. Using intravital microscopy live animals, we report that undergoes rapid and periodic oscillations under basal conditions. Notably, mitochondria vivo behave as a network functionally coupled oscillators, which maintain high level throughout tissue via activity gap junctions. These findings reveal unique aspect relationship between architecture self-organization vivo.
Intravital microscopy has enabled imaging of the dynamics subcellular structures in live animals, thus opening door to investigating membrane trafficking under physiological conditions. Here, we sought determine whether architecture and environment a fully developed tissue influences endocytic processes. To this aim, imaged endocytosis stromal cells rat salivary glands both situ after they were isolated cultured on solid surface. We found that internalization transferrin dextran, two...
Here we describe a procedure to image subcellular structures in live rodents that is based on the use of confocal intravital microscopy. As model organ, salivary glands mice since they provide several advantages. First, can be easily exposed enable access optics, and stabilized facilitate reduction motion artifacts due heartbeat respiration. This significantly facilitates imaging tracking small structures. Second, most cell populations are accessible from surface organ. permits microscopy...
In all the major secretory organs regulated exocytosis is a fundamental process that used for releasing molecules in extracellular space. Molecules destined secretion are packaged into vesicles fuse with plasma membrane upon appropriate stimulus. exocrine glands, large specialized domains of membrane, which form ductal structures direct continuity external environment and exhibit various architectures diameters. recent study, we intravital microscopy to analyze detail dynamics exocytic...
Yes-associated Protein (YAP) is a transcriptional co-activator that regulates cell proliferation and survival by binding to selective set of enhancers for potent target gene activation, but how YAP coordinates these responses unknown. Here, we demonstrate forms liquid-like condensates in the nucleus response macromolecular crowding. Formed within seconds hyperosmotic stress, compartmentalized YAP’s DNA cofactor TEAD1 along with other YAP-related transcription co-activators, including TAZ,...
In the liver, mitochondria are exposed to different concentrations of nutrients due their spatial positioning across periportal (PP) and pericentral (PC) axis. How these sense integrate signals respond maintain homeostasis is not known. Here, we combined intravital microscopy, proteomics, functional assessment investigate mitochondrial heterogeneity in context liver zonation. We found that PP PC morphologically functionally distinct; beta-oxidation was elevated regions, while lipid synthesis...
Abstract Epithelial cells in the skin and other tissues rely on signals from their environment to maintain homeostasis respond injury, G protein-coupled receptors (GPCRs) play a critical role this communication. A better understanding of GPCRs expressed epithelial will contribute relationship between niche could lead developing new therapies modulate cell fate. This study used human primary keratinocytes as model investigate specific regulating proliferation differentiation. We identified...
Epidermal growth factor receptor (EGFR) signaling is frequently dysregulated in various cancers. The ubiquitin ligase Casitas B-lineage lymphoma proto-oncogene (Cbl) regulates degradation of activated EGFR through ubiquitination and acts as an adaptor to recruit proteins required for trafficking. Here, we used stable isotope labeling with amino acids cell culture mass spectrometry compare Cbl complexes or without epidermal (EGF) stimulation. We identified over a hundred novel interactors,...