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2014

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Articles 271 - 299 of 299

Full-Text Articles in Cell Biology

Epigenetic Regulation Of Progenitor Cell Commitment By Hdac3, Mudit Gupta Jan 2014

Epigenetic Regulation Of Progenitor Cell Commitment By Hdac3, Mudit Gupta

Publicly Accessible Penn Dissertations

Tissue-specific progenitor cells emerge during development to expand and differentiate into the multiple cell lineages that populate the embryo. Appropriate differentiation of these precursor cells requires coordinated expression of numerous lineage-specific genes and repression of alternative fate programs. Epigenetic regulators are enzymes capable of activating or silencing large genomic domains by altering histone modifications, DNA methylation status and chromatin organization. Although differentiating progenitor cells undergo epigenetic changes and epigenetic factors are required for appropriate cell behavior, the precise mechanism of how these proteins influence cell fate remains unclear. In this dissertation, I examine the role of histone deacetylase 3 in ...


Recirculation Of Innate Lymphocyte Subsets In The Skin, Skye Geherin Jan 2014

Recirculation Of Innate Lymphocyte Subsets In The Skin, Skye Geherin

Publicly Accessible Penn Dissertations

The trafficking of innate-like lymphocytes, such as γδ T cells and B-1 B cells, has garnered comparatively little attention from the immunological community relative to conventional T and B cells. However, recent studies have shown that innate-like cell subsets are critical for immune regulation and host defense. In this study, we use a classic ovine lymph cannulation model to describe the phenotype and function of γδ T cells migrating through the skin. We find that γδ T cells traveling in the skin-draining afferent lymph are IFN-γ- and/or IL-17-producing effector cells that express high levels of the skin- and inflammation-seeking ...


Role Of Cytoskeletal Remodeling In T Cell Receptor Signaling And Integrin Activation At The Immunological Synapse, Alexander Babich Jan 2014

Role Of Cytoskeletal Remodeling In T Cell Receptor Signaling And Integrin Activation At The Immunological Synapse, Alexander Babich

Publicly Accessible Penn Dissertations

The efficiency of an immune response critically depends on the ability of T cells to respond to antigens. Upon encountering cognate antigenic peptides on the surface of antigen-presenting cells, T cells form a specialized interface, termed the immunological synapse (IS), which serves as the site of information transfer between the cells. This contact zone is characterized by the enrichment of signaling receptors, kinases and adaptor proteins, and is the site of extensive cytoskeletal remodeling. The versatile nature and spatio-temporal regulation of signaling cascades at the IS has long been recognized but the exact mechanisms that coordinate these processes remain poorly ...


Junctional Sarcoplasmic Reticulum Protein Processing And Trafficking In Cardiac Tissue And Primary Cultured Cardiomyocytes, Naama Sleiman Jan 2014

Junctional Sarcoplasmic Reticulum Protein Processing And Trafficking In Cardiac Tissue And Primary Cultured Cardiomyocytes, Naama Sleiman

Wayne State University Dissertations

Junctional SR is an important and unique ER subdomain in the adult myocyte that releases Ca2+ through the actions of an exclusive set of resident proteins. Cardiac calsequestrin (CSQ2) undergoes two co-translational modifications: N-linked glycosylation on 316Asn, and phosphorylation by protein kinase CK2 on a cluster of 3 serines in its tail. In the heart, CSQ2 molecules undergo extensive mannose trimming by ER mannosidase(s), a posttranslational process that often regulates protein breakdown. To investigate CSQ2 protein processing in cardiomyopathy models, studies were performed to test whether CSQ2 glycan structures would be altered in heart tissue from mongrel dogs induced ...


Cxcr2 Macromolecular Complex In Pancreatic Cancer: A Potential Therapeutic Target In Tumor Growth, Shuo Wang Jan 2014

Cxcr2 Macromolecular Complex In Pancreatic Cancer: A Potential Therapeutic Target In Tumor Growth, Shuo Wang

Wayne State University Dissertations

The signaling mediated by the chemokine receptor CXC chemokine receptor 2 (CXCR2) plays an important role in promoting the progression of many cancers, including pancreatic cancer, one of the most lethal human malignancies. CXCR2 possesses a consensus PSD-95/DlgA/ZO-1 (PDZ) motif at its carboxyl termini, which might interact with potential PDZ scaffold/adaptor proteins. We have previously reported that CXCR2 PDZ motif-mediated protein interaction is an important regulator for neutrophil functions. Here, using a series of biochemical assays, we demonstrate that CXCR2 is physically coupled to its downstream effector phospholipase C-β3 (PLC-β3) that is mediated by PDZ scaffold protein ...


Effects Of Altering The Peroxisomal Redox State In Models Of Degenerative Disease, Courtney Rose Giordano Jan 2014

Effects Of Altering The Peroxisomal Redox State In Models Of Degenerative Disease, Courtney Rose Giordano

Wayne State University Dissertations

Peroxisomes are important regulators of cellular redox balance and function as a signaling platform to regulate anti-aging metabolic and communication networks. In addition the organelle has emerged as a major player in maintaining cellular ROS at an optimal level. At such levels, these ROS are involved in initiation of signaling cascades and that produce an array of anti-aging and disease processes. However, as cells age over time, ROS amass within the peroxisome and elsewhere in the cell. This leads to an imbalance in oxidative homeostasis and results in compromised signaling networks. The goal of this dissertation was to treat disease ...


Characterization Of Adult Zebrafish Retinal Regeneration Following Two Different Damage Models, Jennifer Lee Thomas Jan 2014

Characterization Of Adult Zebrafish Retinal Regeneration Following Two Different Damage Models, Jennifer Lee Thomas

Wayne State University Dissertations

Unlike mammals, zebrafish can regenerate all of their retinal neurons through Müller glial cells, which respond to retinal damage by re-entering the cell cycle to create clusters of progenitor cells. The progenitors continue to proliferate as they migrate to the site of damage, where they ultimately differentiate into new retinal neurons. In contrast, Müller glia of the mammalian retina respond to injury with reactive gliosis, which if persistent, can lead to loss of Müller cell function and devastating vision loss. Despite this, multiple lines of evidence suggest that mammalian Müller glial cells possess a latent ability to regenerate retinal neurons ...


Mitochondrial Dynamics: Exploring A Novel Target Against Myocardial Ischemia-Reperfusion Injury, Yi Dong Jan 2014

Mitochondrial Dynamics: Exploring A Novel Target Against Myocardial Ischemia-Reperfusion Injury, Yi Dong

Wayne State University Dissertations

Mitochondrial fusion and fission, collectively termed mitochondrial dynamics, are among the core mechanisms responsible for maintaining mitochondrial health and functional integrity. Dynamin-related protein 1 (DRP1) is a key regulator of mitochondrial fission. Recent studies suggest that i) mitochondrial dynamics, particularly, mitochondrial fission, serves as a mediator of cell fate in the setting of ischemia-reperfusion (IR) injury, and, ii) inhibition of DRP1 and mitochondrial fission provides cardioprotection against IR injury. However, the precise role of DRP1 translocation to mitochondria in the pathogenesis of myocardial ischemia-reperfusion injury has not been established.

Using an established model of hypoxia-reoxygenation (HR) in cultured HL-1 cardiomyocytes ...


Epithelial Cell Shape Changes During Lung Branching Morphogenesis: The Role Of Wnt/Fzd2 Signaling In Directing New Branch Formation, Rachel S. Kadzik Jan 2014

Epithelial Cell Shape Changes During Lung Branching Morphogenesis: The Role Of Wnt/Fzd2 Signaling In Directing New Branch Formation, Rachel S. Kadzik

Publicly Accessible Penn Dissertations

Formation of the intricately branched mammalian lung requires precise coordination between the epithelium and mesenchyme over the course of development. This coordination is mediated by molecular signaling between the two tissue compartments. How these signaling pathways coordinate changes in cellular and tissue morphology to give rise to the highly ramified branched network of the lung is not well understood. In this work, I show that signaling through Frizzled 2 (Fzd2) is required for promoting changes in epithelial cell shape that lead to tissue-level changes needed for branching morphogenesis in the lung. Through analysis of both fixed lungs and live imaging ...


Membrane Forces And Key Protein Determinants Of Hematopoietic Cell Function: Lamins And Myosin-Ii In Hematopoiesis And Cd47 In Immunotherapy Of Cancer, Kyle Spinler Jan 2014

Membrane Forces And Key Protein Determinants Of Hematopoietic Cell Function: Lamins And Myosin-Ii In Hematopoiesis And Cd47 In Immunotherapy Of Cancer, Kyle Spinler

Publicly Accessible Penn Dissertations

Hematopoiesis in human bone marrow generates every second about 105 – 106 anucleated platelets and red blood cells as well as nucleated white blood cells that are capable of infiltrating distant tissues. The thesis begins in the marrow with a description of (1) nuclear membrane ‘lamina’ physicochemical properties that influence marrow-to-circulation trafficking, and proceeds to detail (2) the physicochemical roles of membrane cortex ‘myosin’ in key marrow processes of motility and division as well as platelet biogenesis and disease. The thesis finishes with (3) studies of macrophages in peripheral tissues far from the marrow and aspects of how such ...


Regulation Of Zygotic Transcription And Cell Cycle Checkpoints In Early Embryogenesis, Xiang Maomao Zhang Jan 2014

Regulation Of Zygotic Transcription And Cell Cycle Checkpoints In Early Embryogenesis, Xiang Maomao Zhang

Publicly Accessible Penn Dissertations

For many organisms, the first goal of embryogenesis is to accumulate a large cell population to accommodate gastrulation. To achieve this quickly, embryos employ specialized cell cycles called cleavages that consist of continuous rounds of DNA replication and division. Cell proliferation occurs rapidly because cleavage cycles lack the gap phases and cell cycle checkpoints found in canonical cell cycles. Further, the genetic materials required to sustain cleavage cycles are preloaded during oogenesis, aiding efficient cell cycle progression. After a constant, organism-specific number of cleavages, many metazoan embryos undergo the mid-blastula transition (MBT), which initiates extensive cell cycle remodeling. Cell cycles ...


The Role Of The Exocyst In Membrane Deformation, Cell Migration And Exocytosis, Yuting Zhao Jan 2014

The Role Of The Exocyst In Membrane Deformation, Cell Migration And Exocytosis, Yuting Zhao

Publicly Accessible Penn Dissertations

Dynamic shape changes of the plasma membrane are fundamental to many processes ranging from morphogenesis and cell migration to phagocytosis and viral propagation. In this study, I showed that Exo70, a component of the exocyst complex, induces tubular membrane invaginations towards the lumen of synthetic vesicles in vitro and generates actin-free protrusions on the surface of cells. Analyses using Exo70 mutants suggest that Exo70 generates negative membrane curvature through an oligomerization-based mechanism. The membrane-deformation function of Exo70 is likely to be independent of the other exocyst subunits. Exo70 thus represents a novel membrane-deforming protein for plasma membrane remodeling. Directional cell ...


The Innate Antiviral Effects Of Extracellular Viral Dsrna In Rainbow Trout Cells, Sarah J. Poynter Jan 2014

The Innate Antiviral Effects Of Extracellular Viral Dsrna In Rainbow Trout Cells, Sarah J. Poynter

Theses and Dissertations (Comprehensive)

Viral double-stranded RNA (dsRNA) molecules are a potent pathogen-associated molecular pattern and play a crucial role in the innate immune response. During a viral infection, extracellular and intracellular dsRNA can initiate pathways resulting in the production of type I interferons (IFNs) and interferon-stimulated genes (ISGs). The accumulation of ISGs within a cell results in a protective antiviral state. This study used both commercially available dsRNA (poly I:C) and in vitro transcribed dsRNA molecules, based on the viral hemorrhagic septicemia virus (VHSV) genome sequence, as stimuli to investigate the effects of these molecules on the innate immune response in rainbow ...


Cellular Regulation Of Extension And Retraction Of Pseudopod-Like Blebs Produced By Nanosecond Pulsed Electric Field, Mikhail A. Rassokhin, Andrei G. Pakhomov Jan 2014

Cellular Regulation Of Extension And Retraction Of Pseudopod-Like Blebs Produced By Nanosecond Pulsed Electric Field, Mikhail A. Rassokhin, Andrei G. Pakhomov

Bioelectrics Publications

Recently we described a new phenomenon of anodotropic pseudopod-like blebbing in U937 cells exposed to nanosecond pulsed electric field (nsPEF). In Ca2+ -free buffer such exposure initiates formation of pseudopod-like blebs (PLBs), protrusive cylindrical cell extensions that are distinct from apoptotic and necrotic blebs. PLBs nucleate predominantly on anode-facing cell pole and extend toward anode during nsPEF exposure. Bleb extension depends on actin polymerization and availability of actin monomers. Inhibition of intracellular Ca2+ , cell contractility, and RhoA produced no effect on PLB initiation. Meanwhile, inhibition of WASP by wiskostatin causes dose-dependent suppression of PLB growth. Soon after the ...


Combating Resistance To Epidermal Growth Factor Recpetor Inhibitors In Triple Negative Breast Cancer, Julie Marie Madden Jan 2014

Combating Resistance To Epidermal Growth Factor Recpetor Inhibitors In Triple Negative Breast Cancer, Julie Marie Madden

Wayne State University Dissertations

Triple negative breast cancer (TNBC) patients suffer from a highly malignant and aggressive cancer that lacks an effective targeted therapeutic. Although many TNBCs, both in vitro and in vivo, have increased expression of epidermal growth factor receptor (EGFR), EGFR targeted inhibitors, such as gefitinib (GEF), have yet to demonstrate efficacy. Using mass spectrometry to identify pathways that remain activated in the presence of GEF, we found that components of the mTOR signaling pathway remain phosphorylated. While inhibiting mTOR with temsirolimus (TEM) decreased mTOR signaling, EGFR signaling pathways remained activated and the TNBC cell lines continued to proliferate. However, dual treatment ...


Regulation Of Inositol Biosynthesis And Cellular Consequences Of Inositol Depletion: Implications For The Mechanism Of Action Of Valproate, Rania M. Deranieh Jan 2014

Regulation Of Inositol Biosynthesis And Cellular Consequences Of Inositol Depletion: Implications For The Mechanism Of Action Of Valproate, Rania M. Deranieh

Wayne State University Dissertations

Inositol is a six-carbon cyclitol that is ubiquitous in biological systems. It is a precursor for the synthesis of numerous biologically important compounds, including inositol phosphates and phosphoinositides that are essential for cell function and viability. Inositol compounds play a role in membrane formation, gene regulation, signaling, regulation of ion channels, and membrane trafficking. Furthermore, inositol regulates hundreds of genes, including those involved in the biosynthesis of inositol and phospholipids. While transcriptional regulation of inositol biosynthesis has been extensively studied and well characterized, regulation of inositol biosynthesis at the enzymatic level has not been addressed. The current study shows that ...


Tracing Beta Strands Using Strandtwister From Cryo-Em Density Maps At Medium Resolutions, Dong Si, Jing He Jan 2014

Tracing Beta Strands Using Strandtwister From Cryo-Em Density Maps At Medium Resolutions, Dong Si, Jing He

Computer Science Faculty Publications

Major secondary structure elements such as α helices and β sheets can be computationally detected from cryoelectron microscopy (cryo-EM) density maps with medium resolutions of 5–10 A˚ . However, a critical piece of information for modeling atomic structures is missing, because there are no tools to detect β strands from cryo-EM maps at medium resolutions. We propose a method, StrandTwister, to detect the traces of β strands through the analysis of twist, an intrinsic nature of a β sheet. StrandTwister has been tested using 100 β sheets simulated at 10 A˚ resolution and 39 β sheets computationally detected from cryo-EM ...


Basic Features Of A Cell Electroporation Model: Illustrative Behavior For Two Very Different Pulses, Reuben S. Son, Kyle C. Smith, Thiruvallur R. Gowrishankar, P. Thomas Vernier, James C. Weaver Jan 2014

Basic Features Of A Cell Electroporation Model: Illustrative Behavior For Two Very Different Pulses, Reuben S. Son, Kyle C. Smith, Thiruvallur R. Gowrishankar, P. Thomas Vernier, James C. Weaver

Bioelectrics Publications

Science increasingly involves complex modeling. Here we describe a model for cell electroporation in which membrane properties are dynamically modified by poration. Spatial scales range from cell membrane thickness (5 nm) to a typical mammalian cell radius (10 μm), and can be used with idealized and experimental pulse waveforms. The model consists of traditional passive components and additional active components representing nonequilibrium processes. Model responses include measurable quantities: transmembrane voltage, membrane electrical conductance, and solute transport rates and amounts for the representative "long" and "short" pulses. The long pulse-1.5 kV/cm, 100 μs-evolves two pore subpopulations with a valley ...


Dephosphorylation Of Iqg1 By Cdc14 Temporally Regulates Actin Ring Formation, Daniel Patrick Miller Jan 2014

Dephosphorylation Of Iqg1 By Cdc14 Temporally Regulates Actin Ring Formation, Daniel Patrick Miller

Masters Theses

"Cytokinesis is the final step in cell division when the cell separates the cytoplasm by contracting a ring composed of filamentous actin (F-actin) and type II myosin. Iqg1, an IQGAP family member, is an essential scaffolding protein in budding yeast (S. cerevisiae) required for actin recruitment to, and contraction of, the actomyosin ring. Actin is recruited by the calponin homology domain (CHD) in anaphase after Iqg1 is localized to the bud neck. Consensus sites for the cyclin-dependent kinase (CDK) Cdc28 were identified flanking the CHD. This led us to the hypothesis that phosphorylation of Iqg1 by Cdc28 negatively regulates actin ...


Collagen Attachment To The Substrate Controls Cell Clustering Through Migration, Yue Hou, Laura L. Rodriguez, Juan Wang, Ian C. Schneider Jan 2014

Collagen Attachment To The Substrate Controls Cell Clustering Through Migration, Yue Hou, Laura L. Rodriguez, Juan Wang, Ian C. Schneider

Chemical and Biological Engineering Publications

Cell clustering and scattering play important roles in cancer progression and tissue engineering. While the extracellular matrix (ECM) is known to control cell clustering, much of the quantitative work has focused on the analysis of clustering between cells with strong cell-cell junctions. Much less is known about how the ECM regulates cells with weak cell-cell contact. Clustering characteristics were quantified in rat adenocarcinoma cells, which form clusters on physically adsorbed collagen substrates, but not on covalently attached collagen substrates. Covalently attaching collagen inhibited desorption of collagen from the surface. While changes in proliferation rate could not explain differences seen in ...


Liver And Skeletal Muscle Mitochondria Proteomes Are Altered In Pigs Divergently Selected For Residual Feed Intake, Judson Kyle Grubbs, Elisabeth J. Huff-Lonergan, Nicholas K. Gabler, Jack C. Dekkers, Steven M. Lonergan Jan 2014

Liver And Skeletal Muscle Mitochondria Proteomes Are Altered In Pigs Divergently Selected For Residual Feed Intake, Judson Kyle Grubbs, Elisabeth J. Huff-Lonergan, Nicholas K. Gabler, Jack C. Dekkers, Steven M. Lonergan

Animal Science Publications

Animals selected for residual feed intake (RFI) can be used as a model to elucidate molecular explanations for differences in growth efficiency. The objective of this study was to determine the extent to which the protein profile and posttranslational modifications of mitochondria from skeletal muscle and liver relate to feed efficiency gains in pigs divergently selected for RFI. Mitochondria were isolated from the longissimus dorsi (LD) muscle and the liver from pigs (n = 9 each for the high and low RFI line; BW = 95.8 kg). Mitochondria protein profile differences were determined using two-dimensional difference in gel electrophoresis. Proteins were ...


Dielectric Characterization Of Coastal Cartilage Chondrocytes, Michael W. Stacey, Ahmet C. Sabuncu, Ali Beskok Jan 2014

Dielectric Characterization Of Coastal Cartilage Chondrocytes, Michael W. Stacey, Ahmet C. Sabuncu, Ali Beskok

Bioelectrics Publications

BACKGROUND: Chondrocytes respond to biomechanical and bioelectrochemical stimuli by secreting appropriate extracellular matrix proteins that enable the tissue to withstand the large forces it experiences. Although biomechanical aspects of cartilage are well described, little is known of the bioelectrochemical responses. The focus of this study is to identify bioelectrical characteristics of human costal cartilage cells using dielectric spectroscopy.

METHODS: Dielectric spectroscopy allows non-invasive probing of biological cells. An in house computer program is developed to extract dielectric properties of human costal cartilage cells from raw cell suspension impedance data measured by a microfluidic device. The dielectric properties of chondrocytes are ...


Introduction To Fourth Special Issue On Electroporation-Based Technologies And Treatments, Damijan Miklavčič, Lluis M. Mir, P. Thomas Vernier Jan 2014

Introduction To Fourth Special Issue On Electroporation-Based Technologies And Treatments, Damijan Miklavčič, Lluis M. Mir, P. Thomas Vernier

Bioelectrics Publications

This fourth special electroporation-based technologies and treatments issue of the Journal of Membrane Biology contains reports on recent developments in the field of electroporation by participants in the 7th International Workshop and Postgraduate Course on electroporation based technologies and treatments (EBTT 2013) held in Ljubljana, November 17–23, 2013. The 65 participants included faculty members, invited lecturers, special guests, and young scientists, and students from 16 countries. In addition to lectures on the fundamentals, this year’s sessions included talks on microbial inactivation by pulsed electric fields, modeling of intracellular electroporation, electroporation in food processing, and electrotransfer-facilitated DNA vaccination.


Calpain 5: A Non-Classical Calpain Highly Expressed In The Cns And Localized To Mitochondria And Nuclear Pml Bodies, Ranjana Singh Jan 2014

Calpain 5: A Non-Classical Calpain Highly Expressed In The Cns And Localized To Mitochondria And Nuclear Pml Bodies, Ranjana Singh

Theses and Dissertations--Neuroscience

Calpain 5 (CAPN5) is a non-classical member of the calpain family. It lacks the EF-hand motif characteristic of the classical calpains, calpain 1 and 2, but retains catalytic and Ca2+ binding non EF domains. Tra-3, an ortholog of CAPN5, is involved in necrotic cell death in C.elegans; although specific role of CAPN5 has not been investigated in the mammalian CNS. I compared relative mRNA levels of calpains in rat CNS, which revealed that CAPN5 is the second most highly expressed calpain. We examined relative levels of CAPN5 from late embryonic day 18 to postnatal day 90 and found ...


Structure-Function Analysis Of Zapc, An Ftsz-Ring Stabilizer, In Escherichia Coli Cytokinesis, Lukasz Tchorzewski Jan 2014

Structure-Function Analysis Of Zapc, An Ftsz-Ring Stabilizer, In Escherichia Coli Cytokinesis, Lukasz Tchorzewski

Dissertations and Theses

In Escherichia coli, cell division is defined by the polymerization and constriction of a cytokinetic ring (Z ring) formed by FtsZ, a tubulin-like GTPase, at midcell. Division also involves the formation of a multi-protein complex at midcell known as the divisome. Several divisome proteins promote the assembly/disassembly processes of FtsZ, thereby exercising spatiotemporal control over division. Among FtsZ regulatory proteins are the FtsZ ringassociated proteins (Zap), which either directly or indirectly stabilize the Z-ring by increasing lateral interactions amongst FtsZ protofilaments in the Z-ring. ZapA-D are recruited during early cytokinesis and have overlapping functions in stabilizing FtsZ at midcell ...


Classical And Alternative Nuclear Factor-Kappab In Epithelium: Impacts In Allergic Airway Disease And Avenues For Redox Regulation, Jane Elizabeth Tully Jan 2014

Classical And Alternative Nuclear Factor-Kappab In Epithelium: Impacts In Allergic Airway Disease And Avenues For Redox Regulation, Jane Elizabeth Tully

Graduate College Dissertations and Theses

Nuclear Factor kappaB (NF-êB) is a transcription factor whose activation is increased in settings of allergic asthma. At least two parallel NF-êB pathways exist: the classical pathway, which plays a role in inflammation and cell survival, and the alternative pathway, which regulates lymphoid cell development and organogenesis. The classical NF-êB pathway regulates inflammatory responses derived from lung epithelial cells; however, the role of the alternative pathway in lung epithelial cells remains unclear. We demonstrate that both classical and alternative NF-êB are activated in lung epithelial cells in response to multiple pro-inflammatory agonists, and siRNA-mediated knockdown of alternative NF-êB proteins largely ...


Structural Basis For Phosphorylation And Lysine Acetylation Cross-Talk In A Kinase Motif Associated With Myocardial Ischemia And Cardioprotection, Benjamin L. Parker, Nicholas E. Shepherd, Sophie Trefely, Nolan John Hoffman, Melanie Y. White, Kasper Engholm-Keller, Brett D. Hambly, Martin R. Larsen, David E. James, Stuart J. Cordwell Jan 2014

Structural Basis For Phosphorylation And Lysine Acetylation Cross-Talk In A Kinase Motif Associated With Myocardial Ischemia And Cardioprotection, Benjamin L. Parker, Nicholas E. Shepherd, Sophie Trefely, Nolan John Hoffman, Melanie Y. White, Kasper Engholm-Keller, Brett D. Hambly, Martin R. Larsen, David E. James, Stuart J. Cordwell

Faculty of Health Sciences Publications

Myocardial ischemia and cardioprotection by ischemic pre-conditioning induce signal networks aimed at survival or cell death if the ischemic period is prolonged. These pathways are mediated by protein post-translational modifications that are hypothesized to cross-talk with and regulate each other. Phosphopeptides and lysine-acetylated peptides were quantified in isolated rat hearts subjected to ischemia or ischemic pre-conditioning, with and without splitomicin inhibition of lysine deacetylation. We show lysine acetylation (acetyl-Lys)-dependent activation of AMP-activated protein kinase, AKT, and PKA kinases during ischemia. Phosphorylation and acetyl-Lys sites mapped onto tertiary structures were proximal in >50% of proteins investigated, yet they were mutually ...


Engineered Materials To Measure And Regulate Cell Mechanotransduction, Brandon Lou Blakely Jan 2014

Engineered Materials To Measure And Regulate Cell Mechanotransduction, Brandon Lou Blakely

Publicly Accessible Penn Dissertations

The extracellular environment plays a key role in a wide array of cellular functions including migration, tissue formation, and differentiation. This thesis overviews the design of a molecular sensor to measure cellular forces and a hydrogel system to engineer angiogenic sprouting. We developed molecular force probes (FPs) that report traction forces of adherent cells with high spatial resolution, can be linked to virtually any surface, and do not require monitoring deformations of elastic substrates. FPs consist of DNA hairpins conjugated to fluorophore-quencher pairs that unfold and fluoresce when subjected to specific amounts of force. In chapter two we overview the ...


Regulation Of Cell Signaling By Mig6 And Sprouty2 In Cancers With Egfr Mutations, Alice Macdonald Walsh Jan 2014

Regulation Of Cell Signaling By Mig6 And Sprouty2 In Cancers With Egfr Mutations, Alice Macdonald Walsh

Publicly Accessible Penn Dissertations

Epidermal growth factor receptor (EGFR) mutation and overexpression promote tumorigenesis in multiple cancers. Understanding the complex EGFR regulatory network is critical for developing effective therapeutic interventions. To this end, this work investigated the functions of two incompletely characterized regulators of EGFR trafficking and signaling, mitogen-inducible gene 6 (MIG6) and Sprouty2 (SPRY2), in two cancer settings where EGFR mutation is common, non-small cell lung cancer (NSCLC) and glioblastoma multiforme (GBM). In NSCLC cells, results indicate that MIG6, an endogenous inhibitor of EGFR activity and endocytic adaptor, is surprisingly responsible for at least half of EGFR endocytosis, suggesting that a substantial fraction ...