A5033934751- Extracellular vesicles in disease
- Cellular Mechanics and Interactions
- Cell Adhesion Molecules Research
- MicroRNA in disease regulation
- Protease and Inhibitor Mechanisms
- Axon Guidance and Neuronal Signaling
- Signaling Pathways in Disease
- RNA Interference and Gene Delivery
- Cancer Cells and Metastasis
- RNA Research and Splicing
- Circular RNAs in diseases
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- 3D Printing in Biomedical Research
- RNA modifications and cancer
- Mathematical Biology Tumor Growth
- Hippo pathway signaling and YAP/TAZ
- Microtubule and mitosis dynamics
- Radiomics and Machine Learning in Medical Imaging
- Colorectal Cancer Treatments and Studies
- Cancer Genomics and Diagnostics
- Colorectal Cancer Surgical Treatments
- interferon and immune responses
- Tissue Engineering and Regenerative Medicine
- Lipid Membrane Structure and Behavior
Vanderbilt University Medical Center
2015-2025
Vanderbilt University
2016-2025
Stanford University
2022
Duke University
2020
Weatherford College
2020
Universidade Estadual de Campinas (UNICAMP)
2020
Universidade Federal de São Carlos
2020
Bipar
2015-2019
Vanderbilt-Ingram Cancer Center
2015
Nashville VA Medical Center
2015
Abstract Directional cell movement through tissues is critical for multiple biological processes and requires maintenance of polarity in the face complex environmental cues. Here we use intravital imaging to demonstrate that secretion exosomes from late endosomes required directionally persistent efficient vivo cancer cells. Inhibiting exosome or biogenesis leads defective tumour migration associated with increased formation unstable protrusions excessive directional switching. In vitro r...
Unconventional secretion of exosome vesicles from multivesicular endosomes (MVEs) occurs across a broad set systems and is reported to be upregulated in cancer, where it promotes aggressive behavior. However, regulatory control poorly understood. Using cancer cells, we identified specialized invasive actin structures called invadopodia as specific critical docking sites for CD63- Rab27a-positive MVEs. Thus, inhibition formation greatly reduced into conditioned media. Functionally, addition...
Cancer-associated fibroblasts (CAFs) are major components of the carcinoma microenvironment that promote tumor progression. However, mechanisms by which CAFs regulate cancer cell migration poorly understood. In this study, we show fibronectin (Fn) assembled mediates CAF–cancer association and directional migration. Compared with normal fibroblasts, produce an Fn-rich extracellular matrix anisotropic fiber orientation, guides cells to migrate directionally. align Fn increasing nonmuscle...
Abstract Invadopodia are branched actin-rich structures associated with extracellular matrix (ECM) degradation that collectively form the invasive machinery of aggressive cancer cells. Cortactin is a prominent component and specific marker invadopodia. Amplification cortactin poor prognosis in head neck squamous cell carcinomas (HNSCC), possibly because its activity Although role invadopodia has been attributed to signaling actin assembly, it incompletely understood. We made HNSCC cells...
Cortactin is an actin-binding protein that enriched within the lamellipodia of motile cells and in neuronal growth cones. Here, we report cortactin localized with actin-related (Arp) 2/3 complex at sites actin polymerization lamellipodia. Two distinct sequence motifs contribute to its interaction cortical network: fourth six tandem repeats amino-terminal acidic region (NTA). variants lacking either repeat or NTA failed localize cell periphery. Tandem four was necessary for stably bind...
Secretion of RNAs in extracellular vesicles is a newly recognized form intercellular communication. A potential regulatory protein for microRNA (miRNA) secretion the critical RNA-induced silencing complex (RISC) component Argonaute 2 (Ago2). Here, we use isogenic colon cancer cell lines to show that overactivity KRAS due mutation inhibits localization Ago2 multivesicular endosomes (MVEs) and decreases exosomes. Mechanistically, inhibition mitogen-activated kinase kinases (MEKs) I II, but not...
Mutant KRAS colorectal cancer (CRC) cells release protein-laden exosomes that can alter the tumor microenvironment. To test whether exosomal RNAs also contribute to changes in gene expression recipient cells, and mutant might regulate composition of secreted microRNAs (miRNAs), we compared small matched from isogenic CRC cell lines differing only status. We show profiles are distinct cellular profiles, cluster separately wild-type exosomes. miR-10b was selectively increased exosomes, while...
Abstract Recent studies have shown that circular RNAs (circRNAs) are abundant, widely expressed in mammals, and can display cell-type specific expression. However, how production of circRNAs is regulated their precise biological function remains largely unknown. To study might be during colorectal cancer progression, we used three isogenic colon cell lines differ only KRAS mutation status. Cellular from the parental DLD-1 cells contain both wild-type G13D mutant alleles isogenically-matched...
We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins phosphosites, prioritizes copy number drivers, highlights an oncogenic role for RNA processing genes. investigation mutual exclusivity between FAT1 truncating mutations 11q13.3 amplifications reveals dysregulated actin dynamics as common functional consequence. Phosphoproteomics characterizes two...
Exosomes are extracellular vesicles that influence cellular behavior and enhance cancer aggressiveness by carrying bioactive molecules. The mechanisms regulate exosome secretion poorly understood. Here, we show the actin cytoskeletal regulatory protein cortactin promotes secretion. Knockdown or overexpression of in cells leads to a respective decrease increase secretion, without altering cargo content. Live-cell imaging revealed controls both trafficking plasma membrane docking...
Abstract Small extracellular vesicles called exosomes affect multiple autocrine and paracrine cellular phenotypes. Understanding the function of requires a variety tools, including live imaging. Our previous live-cell reporter, pHluorin-CD63, allows dynamic subcellular monitoring exosome secretion in migrating spreading cells. However, dim fluorescence inability to make stably-expressing cell lines limit its use. We incorporated stabilizing mutation pHluorin moiety, M153R, which now exhibits...
Abstract During the last decade, there has been great interest in elucidating biological role of extracellular vesicles (EVs), particularly, their hormone-like cell-to-cell communication. The field endocrinology is uniquely placed to provide insight into functions EVs, which are secreted from all cells fluids and carry endocrine signals engage paracellular distal interactions. EVs a heterogeneous population membrane-bound varying size, content, bioactivity. specifically packaged with...