A5041615231- Cellular Mechanics and Interactions
- Cellular transport and secretion
- Microtubule and mitosis dynamics
- Cell Adhesion Molecules Research
- Cancer Cells and Metastasis
- Pluripotent Stem Cells Research
- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Metabolism, Diabetes, and Cancer
- 3D Printing in Biomedical Research
- Estrogen and related hormone effects
- Genetics, Aging, and Longevity in Model Organisms
- Cell Image Analysis Techniques
- Mitochondrial Function and Pathology
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced Fluorescence Microscopy Techniques
- Caveolin-1 and cellular processes
- CRISPR and Genetic Engineering
- Developmental Biology and Gene Regulation
- Barrier Structure and Function Studies
- Protein Kinase Regulation and GTPase Signaling
- Axon Guidance and Neuronal Signaling
- Advanced biosensing and bioanalysis techniques
University of Arizona
2013-2023
University of Arizona Cancer Center
2014-2021
University of Tennessee Health Science Center
2021
Rutgers Sexual and Reproductive Health and Rights
2017
Towson University
2017
University of Illinois Chicago
2017
Simpson University
2017
Indiana University
2017
Appalachian State University
2017
Reed College
2017
The mechanical properties of a cell’s microenvironment influence many aspects cellular behavior, including cell migration. Durotaxis, the migration toward increasing matrix stiffness, has been implicated in processes ranging from development to cancer. During durotaxis, stimulation by rigidity leads directed Studies suggest that cells sense stimuli, or mechanosense, through acto-myosin cytoskeleton at focal adhesions (FAs); however, FA actin cytoskeletal remodeling and its role...
Estrogen promotes growth of estrogen receptor-positive (ER+) breast tumors. However, epidemiological studies examining the prognostic characteristics cancer in postmenopausal women receiving hormone replacement therapy reveal a significant decrease tumor dissemination, suggesting that has potential protective effects against cell invasion. Here, we show suppresses invasion ER+ cells by increasing transcription Ena/VASP protein, EVL, which generation suppressive cortical actin bundles inhibit...
While the immediate and transitory response of breast cancer cells to pathological stiffness in their native microenvironment has been well explored, it remains unclear how stiffness-induced phenotypes are maintained over time after cell dissemination vivo. Here, we show that fibrotic-like matrix promotes distinct metastatic cells, which preserved transition softer microenvironments, such as bone marrow. Using differential gene expression analysis stiffness-responsive establish a multigenic...
Insulin-stimulated glucose uptake is known to involve microtubules, although the function of microtubules and microtubule-regulating proteins involved in insulin action are poorly understood. CLASP2, a plus-end tracking microtubule-associated protein (+TIP) that controls microtubule dynamics, was recently implicated as first +TIP associated with insulin-regulated uptake. Here, using protein-specific targeted quantitative phosphoproteomics within 3T3-L1 adipocytes, we discovered regulates...
The human proteome is replete with short linear motifs (SLiMs) of four to six residues that are critical for protein-protein interactions, yet the importance sequence surrounding such underexplored. We devised a proteomic screen examine influence SLiM context on interactions. Focusing EVH1 domain ENAH, an actin regulator highly expressed in invasive cancers, we screened 36-residue proteome-derived peptides and discovered new interaction partners ENAH diverse mechanisms by which influences...
Dendritic spines are the postsynaptic compartment of a neuronal synapse and critical for synaptic connectivity plasticity. A developmental precursor to dendritic spines, filopodia (DF), facilitate formation by sampling environment suitable axon partners during neurodevelopment learning. Despite significance actin cytoskeleton in driving these dynamic protrusions, elongation factors involved not well characterized. We identified Ena/VASP protein EVL as uniquely required morphogenesis dynamics...
Atypical protein kinase C (aPKC) isoforms ζ and λ interact with polarity complex Par3 are evolutionarily conserved regulators of cell polarity. Prkcz encodes aPKC-ζ PKM-ζ, a truncated, neuron-specific alternative transcript, Prkcl aPKC-λ. Here we show that, in embryonic hippocampal neurons, two aPKC isoforms, aPKC-λ expressed. The localization these is spatially distinct polarized neuron. aPKC-λ, as well Par3, localizes at the presumptive axon, whereas PKM-ζ distributed non-axon-forming...
<h3>Abstract</h3> Cell cryopreservation improves reproducibility and enables flexibility in experimental design. Although conventional freezing methodologies have been used to preserve primary neurons, poor cell viability reduced survival severely limited their utility. We screened several high-performance media found that CryoStor10 (CS10) provided superior cryoprotection mouse embryonic cortical neurons compared other commercially-available or traditional reagents, permitting the recovery...
PKCι is essential for the establishment of epithelial polarity and normal assembly tight junctions. We find that knockdown does not compromise steady-state distribution most junction proteins but results in increased transepithelial resistance (TER) decreased paracellular permeability. Analysis levels components demonstrates claudin-2 protein are decreased. However, other proteins, such as claudin-1, ZO-1, occludin, unchanged. Incubation with an aPKC pseudosubstrate recapitulates phenotype...
We investigated the genome of a 5-year-old male who presented with global developmental delay (motor, cognitive, and speech), hypotonia, possibly ataxia, cerebellar hypoplasia unknown origin. Whole sequencing (WGS) mRNA (RNA-seq) were performed on family having an affected proband, his unaffected parents, maternal grandfather. To explore molecular functional consequences variant, we cell proliferation assays, quantitative real-time PCR (qRT-PCR) array, immunoblotting, calcium imaging,...
Metazoan proteomes contain many paralogous proteins that have evolved distinct functions. The Ena/VASP family of actin regulators consists three members share an EVH1 interaction domain with a 100 % conserved binding site. A proteome-wide screen revealed photoreceptor cilium regulator (PCARE) as high-affinity ligand for ENAH EVH1. Here, we report the surprising observation PCARE is ~100-fold specific over paralogs VASP and EVL can selectively bind inhibit ENAH-dependent adhesion in cells....
An abstract is not available for this content so a preview has been provided. As you have access to content, full PDF via the ‘Save PDF’ action button.
The mechanical microenvironment of primary breast tumors plays a substantial role in promoting tumor progression. While the transitory response cancer cells to pathological stiffness their native has been well described, it is still unclear how stimuli influence distant, late-stage metastatic phenotypes across time and space absentia. Here, we show that promotes stable, non-genetically heritable cells. This memory instructs adopt maintain increased cytoskeletal dynamics, traction force, 3D...
The mechanical microenvironment of primary breast tumors plays a substantial role in promoting tumor progression1. While the transitory response cancer cells to pathological stiffness their native has been well described2, it is still unclear how stimuli influence distant, late-stage metastatic phenotypes across time and space absentia. Here, we show that promotes stable, non-genetically heritable cells. This memory instructs adopt maintain increased cytoskeletal dynamics, traction force, 3D...
e15235 Background: Loss of cell polarity, tissue organization and epithelial-mesenchymal transition are associated with progression along the adenoma-carcinoma axis in many cancers. Atypical Protein Kinase C (aPKC) isoforms aPKCzeta/iota form a complex polarity proteins such as Par3/Par6 establish cell-cell adhesion epithelial polarity. Recently, we have described that novel isoform aPKC, PKMzeta, can biochemically compete for binding Par3 disrupt aPKCzeta/iota-Par3 (Proc Natl Acad Sci U S...
G2L1 is a member of the plus-end tracking (+TIP) microtubule (MT)-associated protein family. coordinates cooperativity between MTs and actin was recently detected in an adipocyte CLASP2 interactome. Since has been linked to insulin action, both play unknown role we chose study within 3T3-L1 adipocytes by performing first-ever Using commercially available antibody for two antibodies epitope-tagged, overexpressed G2L1, performed multiple affinity purification coupled with mass spectrometry...
Abstract Metazoan proteomes contain many paralogous proteins that have evolved distinct functions. The Ena/VASP family of actin regulators consists three members share an EVH1 interaction domain with a 100% conserved binding site. A proteome-wide screen revealed ciliary protein PCARE as high-affinity ligand for ENAH EVH1. Here we report the surprising observation is ~100-fold specific over paralogs VASP and EVL can selectively bind inhibit ENAH-dependent adhesion in cells. Specificity arises...