A5089241896- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Advanced Fluorescence Microscopy Techniques
- Ubiquitin and proteasome pathways
- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- Erythrocyte Function and Pathophysiology
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
- Calcium signaling and nucleotide metabolism
- Advanced Biosensing Techniques and Applications
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Mitochondrial Function and Pathology
- Cancer Diagnosis and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Pancreatic function and diabetes
- Angiogenesis and VEGF in Cancer
- PI3K/AKT/mTOR signaling in cancer
- Cancer Research and Treatments
- Virus-based gene therapy research
- RNA Research and Splicing
- Protease and Inhibitor Mechanisms
- Signaling Pathways in Disease
- Autophagy in Disease and Therapy
- Lipid metabolism and biosynthesis
National Institutes of Health
2016-2025
National Cancer Institute
2016-2025
Center for Cancer Research
2016-2025
Bethesda University
2013-2023
Clinical Research Consortium
2022
National Institute of Dental and Craniofacial Research
2011-2020
ORCID
2017
The University of Tokyo
2012
Memorial Sloan Kettering Cancer Center
2011
Louisiana State University Health Sciences Center Shreveport
2011
Carbon nanotube-based drug delivery holds great promise for cancer therapy. Herein we report the first targeted, in vivo killing of cells using a drug-single wall carbon nanotube (SWNT) bioconjugate, and demonstrate efficacy superior to nontargeted bioconjugates. First line anticancer agent cisplatin epidermal growth factor (EGF) were attached SWNTs specifically target squamous cancer, control was SWNT-cisplatin without EGF. Initial vitro imaging studies with head neck carcinoma (HNSCC)...
Tissue remodeling processes critically depend on the timely removal and of preexisting collagen scaffolds. Nevertheless, many aspects related to turnover this abundant extracellular matrix component in vivo are still incompletely understood. We therefore took advantage recent advances optical imaging develop an assay visualize situ identify cell types molecules involved process. Collagen introduced into dermis mice underwent cellular endocytosis a partially metalloproteinase–dependent manner...
Systemic Candida albicans infection causes high morbidity and mortality is associated with neutropenia; however, the roles of other innate immune cells in pathogenesis are poorly defined. Here, using a mouse model systemic candidiasis, we found that resident macrophages accumulated kidney, main target organ infection, formed direct contacts fungus vivo mainly within first few hours after infection. Macrophage accumulation contact were both markedly reduced mice lacking chemokine receptor...
Clathrin-independent endocytosis internalizes plasma membrane proteins that lack cytoplasmic sequences recognized by clathrin adaptor proteins. There is evidence for different clathrin-independent pathways but whether they share common features has not been systematically tested. Here, we examined CD59, an endogenous glycosylphosphatidyl inositol-anchored protein (GPI-AP), and major histocompatibility class I (MHCI), endogenous, integral protein, entered cells through a mechanism followed...
The trafficking of two plasma membrane (PM) proteins that lack clathrin internalization sequences, major histocompatibility complex class I (MHCI), and interleukin 2 receptor alpha subunit (Tac) was compared with PM internalized via clathrin. MHCI Tac were into endosomes distinct from those containing cargo. At later times, a fraction these membranes observed in Arf6-associated, tubular recycling whereas another acquired early endosomal autoantigen 1 (EEA1) before fusion the "classical"...
Plasma membrane proteins that are internalized independently of clathrin, such as major histocompatibility complex class I (MHCI), in vesicles fuse with the early endosomes containing clathrin-derived cargo. From there, MHCI is either transported to late endosome for degradation or recycled back plasma via tubular structures lack clathrin-dependent recycling cargo, e.g., transferrin. Here, we show small GTPase Rab22a associated these intermediates MHCI. Expression a dominant negative mutant...
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...
Histamine-induced vascular leakage is an integral component of many highly prevalent human diseases, including allergies, asthma and anaphylaxis. Yet, how histamine induces the disruption endothelial barrier not well defined. By using genetically modified animal models, pharmacologic inhibitors a synthetic biology approach, here we show that small GTPase RhoA mediates histamine-induced leakage. Histamine causes rapid formation focal adherens junctions, disrupting by acting on H1R Gαq-coupled...
Recent studies revealed that a class III semaphorin, semaphorin 3E (Sema3E), acts through single-pass transmembrane receptor, plexin D1, to provide repulsive cue for D1-expressing endothelial cells, thus providing highly conserved and developmentally regulated signaling system guiding the growth of blood vessels. We show here Sema3E as potent inhibitor adult tumor-induced angiogenesis. Activation D1 by causes rapid disassembly integrin-mediated adhesive structures, thereby inhibiting cell...
Despite our improved understanding of cancer, the 5-year survival rate for head and neck squamous cell carcinomas (HNSCC) patients remains relatively unchanged at 50% past three decades. HNSCCs often metastasize to locoregional lymph nodes, node involvement represents one most important prognostic factors poor clinical outcome. Among multiple dysregulated molecular mechanism in HNSCCs, emerging basic, preclinical, findings support importance mTOR signaling route HNSCC progression. Indeed, we...
Interfering with a specific G protein–coupled receptor pathway may provide therapeutic approach to blocking metastasis of some forms breast cancer.
Physiologic turnover of interstitial collagen is mediated by a sequential pathway in which fragmented pericellular collagenases, endocytosed receptors, and routed to lysosomes for degradation cathepsins. Here, we use intravital microscopy investigate if malignant tumors, are characterized high rates extracellular matrix turnover, utilize similar pathway. Tumors epithelial, mesenchymal, or neural crest origin all display vigorous endocytic degradation. The cells engaged this process...
Significance Superresolution microscopy has made much progress in improving resolution and imaging speed over the past several years, but ability to image below diffraction limit thick scattering specimens not kept pace. In many interesting samples, such as Caenorhabditis elegans, Drosophila melanogaster , mouse, or human tissues, is limited primarily by rather than diffraction. this paper, we show that combination of multiphoton excitation with multifocal structured illumination gives high...
The actin cytoskeleton plays crucial roles in many cellular processes, including regulated secretion. However, the mechanisms controlling F-actin dynamics this process are largely unknown. Through 3D time-lapse imaging a secreting organ, we show that is actively disassembled along apical plasma membrane at site of secretory vesicle fusion and re-assembled directionally on membranes. Moreover, pore formation PIP2 redistribution precedes myosin recruitment to Finally, essential for branched...
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...