A5028921014- Cellular Mechanics and Interactions
- Cardiomyopathy and Myosin Studies
- Muscle Physiology and Disorders
- Cellular transport and secretion
- Cell Image Analysis Techniques
- Wnt/β-catenin signaling in development and cancer
- Microtubule and mitosis dynamics
- Cell Adhesion Molecules Research
- Force Microscopy Techniques and Applications
- Tissue Engineering and Regenerative Medicine
- Cancer-related gene regulation
- Celiac Disease Research and Management
- RNA Research and Splicing
- Cardiovascular Effects of Exercise
- Skin and Cellular Biology Research
- Digestive system and related health
- Nuclear Structure and Function
- AI in cancer detection
- Image Processing Techniques and Applications
- Extracellular vesicles in disease
- Erythrocyte Function and Pathophysiology
- Caveolin-1 and cellular processes
- 3D Printing in Biomedical Research
- Genetic and Kidney Cyst Diseases
- Biochemical Analysis and Sensing Techniques
Vanderbilt University
2016-2025
Vanderbilt University Medical Center
2011-2025
St. Matthew's University
2017-2021
Vanderbilt Health
2017-2019
Nashville Oncology Associates
2012-2014
National Heart Lung and Blood Institute
2009
Yale University
2002-2005
Institut thématique Génétique, génomique et bioinformatique
2001-2004
Whitney Museum of American Art
2003
University of Vermont
1999-2000
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...
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...
For decades, enterocyte brush border microvilli have been viewed as passive cytoskeletal scaffolds that serve to increase apical membrane surface area. However, recent studies revealed in the vitro context of isolated borders, myosin-1a (myo1a) powers sliding microvillar along core actin bundles. This activity also leads shedding small vesicles from tips, suggesting may function vesicle-generating organelles vivo. In this study, we present data support hypothesis, showing release unilamellar...
To develop our understanding of myosin-1a function in vivo, we have created a mouse line null for the gene. Myosin-1a knockout mice demonstrate no overt phenotypes at whole animal level but exhibit significant perturbations and signs stress cellular level. Among these are defects microvillar membrane morphology, distinct changes brush-border organization, loss numerous cytoskeletal components from brush border, redistribution intermediate filament proteins into border. We also observed...
All cell functions that involve membrane deformation or a change in shape (e.g., endocytosis, exocytosis, motility, and cytokinesis) are regulated by tension. While molecular contacts between the plasma underlying actin cytoskeleton known to make significant contributions tension, little is about molecules mediate these interactions. We used an optical trap directly probe determinants of tension isolated organelles living cells. Here, we show class I myosins, family membrane-binding,...
Intestinal tuft cells are a rare, poorly understood cell type recently shown to be critical mediator of 2 immune response helminth infection. Here, we present advances in segmentation algorithms and analytical tools for multiplex immunofluorescence (MxIF), platform that enables iterative staining over 60 antibodies on single tissue section. These refinements have enabled comprehensive analysis number, distribution, protein expression profiles as function anatomical location physiological...
Microvillus inclusion disease (MVID) is a severe form of congenital diarrhea that arises from inactivating mutations in the gene encoding myosin Vb (MYO5B). We have examined association MYO5B and disruption microvillar assembly polarity enterocytes. Stable knockdown (MYO5B-KD) CaCo2-BBE cells elicited loss microvilli, alterations junctional claudins, apical basolateral trafficking; however, no microvillus inclusions were observed MYO5B-KD cells. Expression WT restored microvilli; expression...
The sarcomere is the contractile unit within cardiomyocytes driving heart muscle contraction. We sought to test mechanisms regulating actin and myosin filament assembly during formation. Therefore, we developed an assay using human monitor assembly. report a population of stress fibers, similar arcs in non-muscle cells, which are essential precursors. show sarcomeric filaments arise directly from fibers. This requires formins (e.g., FHOD3), IIA IIB. Furthermore, short cardiac II grow form...
Next-generation sequencing has enabled precision therapeutic approaches that have improved the lives of children with rare diseases. Congenital diarrhea and enteropathies (CODEs) are associated high morbidity mortality. Although treatment these disorders is largely supportive, emerging targeted therapies based on genetic diagnoses include specific diets, pharmacologic treatments, surgical interventions. We analyzed exomes or genomes infants suspected monogenic congenital diarrheal disorders....
The brush border domain at the apex of intestinal epithelial cells is primary site nutrient absorption in tract and surface interaction with microbes that reside lumen. Because positioned such a critical physiological interface, we set out to create comprehensive list proteins this using shotgun mass spectrometry. resulting proteome contains 646 diverse functions. In addition expected collection processing transport components, also identified molecules function regulation actin dynamics,...
Cells communicate with neighboring cells and condition their local environment by secreting soluble factors into the extracellular space. These well-studied facets of cell biology are essential for establishment maintenance physiological homeostasis. However, accumulating evidence has revealed that specific ligands, enzymes, macromolecules distributed space virtue association small vesicles, which released a variety types. Although biological significance such vesicles was initially debated,...