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2018

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Articles 1 - 30 of 308

Full-Text Articles in Cell Biology

Hla-Do Modulates The Diversity Of The Mhc-Ii Self-Peptidome, Padma P. Nanaware, Mollie M. Jurewicz, John D. Leszyk, Scott A. Shaffer, Lawrence J. Stern Dec 2018

Hla-Do Modulates The Diversity Of The Mhc-Ii Self-Peptidome, Padma P. Nanaware, Mollie M. Jurewicz, John D. Leszyk, Scott A. Shaffer, Lawrence J. Stern

Open Access Articles

Presentation of antigenic peptides on MHC-II molecules is essential for tolerance to self and for initiation of immune responses against foreign antigens. DO (HLA-DO in humans, H2-O in mice) is a non-classical MHC-II protein that has been implicated in control of autoimmunity and regulation of neutralizing antibody responses to viruses. These effects likely are related to a role of DO in selecting MHC-II epitopes, but previous studies examining the effect of DO on presentation of selected CD4 T cell epitopes have been contradictory. To understand how DO modulates MHC-II antigen presentation, we characterized the full spectrum of peptides presented by ...


Chemically Modified Monolayer Surfaces Influence Valvular Interstitial Cell Attachment And Differentiation For Heart Valve Tissue Engineering, Matthew N. Rush Dec 2018

Chemically Modified Monolayer Surfaces Influence Valvular Interstitial Cell Attachment And Differentiation For Heart Valve Tissue Engineering, Matthew N. Rush

Nanoscience and Microsystems ETDs

As a cell mediated-process, valvular heart disease (VHD) results in significant morbidity and mortality world-wide. In the US alone, valvular heart disease VHD is estimated to affect 2.5% of the population with a disproportionate impact on an increasing elderly populous. It is well understood that the primary driver for valvular calcification is the differentiation of valvular interstitial cells (VICs) into an osteoblastic-like phenotype. However, the factors leading to the onset of osteoblastic-like VICs (obVICs) and resulting calcification are not fully understood and a more complete characterization of VIC differentiation and phenotypic change is required before treatment of valve disease ...


Regulation Of Canonical And Non-Canonical Hippo Pathway Components In Mitosis And Cancer, Seth Stauffer Dec 2018

Regulation Of Canonical And Non-Canonical Hippo Pathway Components In Mitosis And Cancer, Seth Stauffer

Theses & Dissertations

The Hippo pathway is conserved regulator of organ size through control of proliferation, apoptosis, and stem-cell self-renewal. In addition to this important function, many of the canonical signaling members have also been shown to be regulated during mitosis. Importantly, Hippo pathway components are frequently dysregulated in cancers and have attracted attention as possible targets for improved cancer therapeutics. Further exploration of Hippo-YAP (yes-associated protein) signaling has revealed new regulators and effectors outside the canonical signaling network and has revealed a larger non-canonical network of signaling proteins in which canonical Hippo pathway components crosstalk with important cellular homeostasis and apoptosis signaling ...


Manganese Influx And Expression Of Zip8 Is Essential In Primary Myoblasts And Contributes To Activation Of Sod2, Shellaina J. V. Gordon, Daniel E. Fenker, Katherine E. Vest, Teresita Padilla-Benavides Dec 2018

Manganese Influx And Expression Of Zip8 Is Essential In Primary Myoblasts And Contributes To Activation Of Sod2, Shellaina J. V. Gordon, Daniel E. Fenker, Katherine E. Vest, Teresita Padilla-Benavides

University of Massachusetts Medical School Faculty Publications

Trace elements such as copper (Cu), zinc (Zn), iron (Fe), and manganese (Mn) are enzyme cofactors and second messengers in cell signaling. Trace elements are emerging as key regulators of differentiation and development of mammalian tissues including blood, brain, and skeletal muscle. We previously reported an influx of Cu and dynamic expression of various metal transporters during differentiation of skeletal muscle cells. Here, we demonstrate that during differentiation of skeletal myoblasts an increase of additional trace elements such as Mn, Fe and Zn occurs. Interestingly the Mn increase is concomitant with increased Mn-dependent SOD2 levels. To better understand the Mn ...


The Effects Of Sugars On Lactobacillus Casei Growth, Alexis Felty, Sidney Gerkin, Taylor Kowalski, Parker Williams Dec 2018

The Effects Of Sugars On Lactobacillus Casei Growth, Alexis Felty, Sidney Gerkin, Taylor Kowalski, Parker Williams

Undergraduate Research Symposium (URS)

The Western culture tends to deem the Eastern culture as obese and unhealthy due to the large amounts of saturated fats and abundance of sugars that it consumes. Some studies argue that Lactobacillus casei can alter health and researchers are attempting to prove that different sugars, natural or artificial, have different effects on the growth of L. casei [1]. L. casei was chosen as the experimental model due to easily replicable growing conditions and the importance of the bacteria in the gut microbiome.

Sugar-bacteria solutions were created and their turbidities were taken to quantify the amount of bacteria growth after ...


Analyzing The Efficacy Of Natural Baby Soaps For The Elimination Of Bacterial Colonization On Bath Toys, Abigail Rost, Jacqueline Benitez, Mira Nicpon, Katelyn Mclaughlin Dec 2018

Analyzing The Efficacy Of Natural Baby Soaps For The Elimination Of Bacterial Colonization On Bath Toys, Abigail Rost, Jacqueline Benitez, Mira Nicpon, Katelyn Mclaughlin

Undergraduate Research Symposium (URS)

Recent studies have discovered that water-retaining bath toys harbor a high amount of potential pathogens due to available nutrients in baby soaps. Unfortunately , these bath toys can be a source for infection or disease for the children playing with them. In order to investigate the efficacy of baby soaps on the elimination of bacteria on bath toys, rubber ducks were coated with E. coli and then were washed with an organic or non-organic baby soap. It was hypothesized that organic soap would be more efficient at eliminating bacteria due to its antibacterial properties. Through this experiment, it was found that ...


Vitamin E: A Possible Preventative Measure For Cte, Dylan Roth, Cameron Dargis Dec 2018

Vitamin E: A Possible Preventative Measure For Cte, Dylan Roth, Cameron Dargis

Undergraduate Research Symposium (URS)

Introduction

This experiment is aimed to aide all future athletes.

•The brain injury known as CTE can only be diagnosed after death and upon autopsy.

•Upon research, what causes this is non-heme Iron deposits in the brain cause radical oxygen species that damage the nerve cells.

•Causes many different mental and physical problems

•Research on Vitamin E showed that it can accept radical oxygen species and increase neurological health.

•We will be testing these affects on yeast samples

Hypothesis

If yeast is treated with Vitamin E before being exposed to radical oxygen species via non-heme iron, then it will have ...


Trisomy Silencing By Xist Normalizes Down Syndrome Cell Pathogenesis Demonstrated For Hematopoietic Defects In Vitro, Jen-Chieh Chiang, Jun Jiang, Peter E. Newburger, Jeanne B. Lawrence Dec 2018

Trisomy Silencing By Xist Normalizes Down Syndrome Cell Pathogenesis Demonstrated For Hematopoietic Defects In Vitro, Jen-Chieh Chiang, Jun Jiang, Peter E. Newburger, Jeanne B. Lawrence

Open Access Articles

We previously demonstrated that an integrated XIST transgene can broadly repress one chromosome 21 in Down syndrome (DS) pluripotent cells. Here we address whether trisomy-silencing can normalize cell function and development sufficiently to correct cell pathogenesis, tested in an in vitro model of human fetal hematopoiesis, for which DS cellular phenotypes are best known. XIST induction in four transgenic clones reproducibly corrected over-production of megakaryocytes and erythrocytes, key to DS myeloproliferative disorder and leukemia. A contrasting increase in neural stem and iPS cells shows cell-type specificity, supporting this approach successfully rebalances the hematopoietic developmental program. Given this, we next used ...


Autophagy In Crop Plants: What's New Beyond Arabidopsis?, Jie Tang, Diane C. Bassham Dec 2018

Autophagy In Crop Plants: What's New Beyond Arabidopsis?, Jie Tang, Diane C. Bassham

Genetics, Development and Cell Biology Publications

Autophagy is a major degradation and recycling pathway in plants. It functions to maintain cellular homeostasis and is induced by environmental cues and developmental stimuli. Over the past decade, the study of autophagy has expanded from model plants to crop species. Many features of the core machinery and physiological functions of autophagy are conserved among diverse organisms. However, several novel functions and regulators of autophagy have been characterized in individual plant species. In light of its critical role in development and stress responses, a better understanding of autophagy in crop plants may eventually lead to beneficial agricultural applications. Here, we ...


Using Arabidopsis Mesophyll Protoplasts To Study Unfolded Protein Response Signaling, Yan Bao, Diane C. Bassham Dec 2018

Using Arabidopsis Mesophyll Protoplasts To Study Unfolded Protein Response Signaling, Yan Bao, Diane C. Bassham

Genetics, Development and Cell Biology Publications

Various environmental stresses or artificial reagents can trigger unfolded protein accumulation in the endoplasmic reticulum (ER) due to the folding capacity of the ER being exceeded. This is termed ER stress, and triggers the unfolded protein response (UPR). Assays for activation of the UPR in plants include Tunicamycin (Tm)- or dithiothreitol (DTT)-mediated root growth inhibition, analysis of splicing of the UPR-responsive transcription factor bZIP60 (basic Leucine Zipper Domain 60), and upregulation of relevant UPR genes. We provide here a quick and robust method to detect UPR signaling in Arabidopsis thaliana protoplasts. This assay can also be applied to other ...


Two Contrasting Classes Of Nucleolus-Associated Domains In Mouse Fibroblast Heterochromatin, Anastassiia Vertii, Jianhong Ou, Jun Yu, Aimin Yan, Hervé Pagès, Haibo Liu, Lihua Julie Zhu, Paul D. Kaufman Dec 2018

Two Contrasting Classes Of Nucleolus-Associated Domains In Mouse Fibroblast Heterochromatin, Anastassiia Vertii, Jianhong Ou, Jun Yu, Aimin Yan, Hervé Pagès, Haibo Liu, Lihua Julie Zhu, Paul D. Kaufman

University of Massachusetts Medical School Faculty Publications

In interphase eukaryotic cells, almost all heterochromatin is located adjacent to the nucleolus or to the nuclear lamina, thus defining Nucleolus Associated Domains (NADs) and Lamina Associated Domains (LADs), respectively. Here, we determined the first genome-scale map of murine NADs in mouse embryonic fibroblasts (MEFs) via deep sequencing of chromatin associated with purified nucleoli. We developed a Bioconductor package called NADfinder and demonstrated that it identifies NADs more accurately than other peak-calling tools, due to its critical feature of chromosome-level local baseline correction. We detected two distinct classes of NADs. Type I NADs associate frequently with both the nucleolar periphery ...


Investigations Of Hp1 And Insulator Partner Protein 1 (Hipp1), Steve Ehren Glenn Dec 2018

Investigations Of Hp1 And Insulator Partner Protein 1 (Hipp1), Steve Ehren Glenn

Theses and Dissertations

Drosophila HP1 and Insulator Partner Protein 1 (HIPP1) is the homologue of the human co-repressor Chromodomain Y family of proteins that repress neuronal gene expression in mammals. HIPP1 was identified by its extensive co-localization with Heterochromatin Protein 1a (HP1a) in heterochromatic regions of the genome and insulator binding proteins in euchromatic regions. The majority of HIPP1 binding to euchromatin is at binding sites for Drosophila Suppressor of Hairy-wing [Su(Hw)]. Su(Hw) is a zinc finger DNA binding protein that functions as an insulator, activator, and repressor. Transcriptional regulation by Su(Hw) is essential in the ovary and testis, where ...


Evaluation Of Motor Cortex Neuronal Morphology In Developmental Hyperserotonemia Rat Model, Colten Z. Dillinger Dec 2018

Evaluation Of Motor Cortex Neuronal Morphology In Developmental Hyperserotonemia Rat Model, Colten Z. Dillinger

MSU Graduate Theses

Fetal serotonin levels are involved in the development of the serotonergic system in an autoregulatory manner as well as the organization and connectivity of non-serotonergic neurons. Insufficient serotonin levels during development result in improper neuronal maturation and decreased synaptogenesis. Conversely, excess developmental serotonin levels can alter the progression of serotonergic neurons, ultimately resulting in a chronic decrease of serotonin in the developed brain via a negative feedback mechanism. There is a known correlation between autistic patients and chronically decreased brain serotonin concentrations; this is potentially implicated in the impaired development of the autistic brain. Incomplete or delayed development of motor ...


Epidermal Growth Factor-Like Ligands Regulate Dimer Selection., Jamie S. Rush Dec 2018

Epidermal Growth Factor-Like Ligands Regulate Dimer Selection., Jamie S. Rush

Electronic Theses and Dissertations

There are thirteen known endogenous EGF-like ligands. We previously reported that Betacellulin (BTC) increases ligand-mediated corneal wound healing more than Epidermal Growth Factor (EGF) [Peterson et al. (2014) IOVS 55(5):2870-80], although the molecular reason for this is unknown. Despite being better at promoting wound healing via enhanced cell migration, BTC has reduced receptor affinity and weaker induction of EGFR phosphorylation. These data indicate that BTC’s response is not due to enhanced affinity or EGFR-kinase activity. Receptor phosphorylation and proximity ligation assays indicate that BTC treatment significantly increases ErbB3 phosphorylation and EGFR:ErbB3 heterodimers. BTC traffics EGFR at ...


Il-12 Gene Electrotransfer Triggers A Change In Immune Response Within Mouse Tumors, Guilan Shi, Chelsea Edelblute, Sezgi Arpag, Cathryn Lundberg, Richard Heller Dec 2018

Il-12 Gene Electrotransfer Triggers A Change In Immune Response Within Mouse Tumors, Guilan Shi, Chelsea Edelblute, Sezgi Arpag, Cathryn Lundberg, Richard Heller

Bioelectrics Publications

Metastatic melanoma is an aggressive skin cancer with a relatively low survival rate. Immune-based therapies have shown promise in the treatment of melanoma, but overall complete response rates are still low. Previous studies have demonstrated the potential of plasmid IL-12 (pIL-12) delivered by gene electrotransfer (GET) to be an effective immunotherapy for melanoma. However, events occurring in the tumor microenvironment following delivery have not been delineated. Therefore, utilizing a B16F10 mouse melanoma model, we evaluated changes in the tumor microenvironment following delivery of pIL-12 using different GET parameters or injection of plasmid alone. The results revealed a unique immune cell ...


Prioritizing Chemical Constituents In Tobacco Products And Smoke To Predict Developmental Osteotoxicity In Human Embryonic Stem Cells, Joseph Madrid Dec 2018

Prioritizing Chemical Constituents In Tobacco Products And Smoke To Predict Developmental Osteotoxicity In Human Embryonic Stem Cells, Joseph Madrid

Electronic Theses, Projects, and Dissertations

Though it is well known that tobacco related products can cause prenatal maldevelopment, very little is known on how tobacco products affect bone tissue as it develops in the embryo. Identifying which chemicals can induce the greatest harm to the prenatal skeletal system is an improbable task as there are over 7,000 chemicals in tobacco smoke alone. We hypothesized that the Toxicological Priority Index (ToxPI) program can be used to rank osteogenic cytotoxicity potential to aid in the assessment of what chemicals out of the thousands can cause osteogenic differentiation inhibition. ToxPI aggregates information from various assays and incorporates ...


Data On Spectrum-Based Fluorescence Resonance Energy Transfer Measurement Of E. Coli Multidrug Transporter Acrb, Yuguang Cai, Thomas E. Wilkop, Yinan Wei Dec 2018

Data On Spectrum-Based Fluorescence Resonance Energy Transfer Measurement Of E. Coli Multidrug Transporter Acrb, Yuguang Cai, Thomas E. Wilkop, Yinan Wei

Chemistry Faculty Publications

This paper presented the dataset of correction parameters used in the determination of the energy transfer efficiencies from the spectrum-based fluorescence resonance energy transfer (FRET) measurement in a trimeric membrane protein AcrB. The cyan fluorescent protein (CFP) and yellow fluorescent protein (YPet) were used as the donor and acceptor, respectively. Two AcrB fusion proteins were constructed, AcrB-CFP and AcrB-YPet. The proteins were co-expressed in Escherichia coli cells, and energy transfer efficiency were determined in live cells. To obtain reliable energy transfer data, a complete set of correction parameters need to be first determined to accommodate for factors such as background ...


Detection And Treatment Of Critical Illnesses Using Oligonucleotides, Kevin Thomas Urak Dec 2018

Detection And Treatment Of Critical Illnesses Using Oligonucleotides, Kevin Thomas Urak

Theses and Dissertations

Sepsis is among the most prevalent diagnosed critical illnesses in the United States today. Although advances have reduced the overall morbidity and mortality associated with this illness, the enormous number of deaths associated with it shows a need for improved diagnostic and therapeutic optionsgent. Our laboratory has utilized RNA based technologies to aid in the treatment of histone induced multiple organ dysfunction syndrome seen in sepsis.

Histones are proteins found in the nucleus of every cell in our body and have been shown to be released during sepsis. Such release induces damage to other cells, causing a feed forward cycle ...


Regulator Of G Protein Signaling 2 (Rgs2) In Preeclampsia: Association, Consequence, And Cause, Katherine Perschbacher Dec 2018

Regulator Of G Protein Signaling 2 (Rgs2) In Preeclampsia: Association, Consequence, And Cause, Katherine Perschbacher

Theses and Dissertations

Increased signaling of various hormones through their cognate G Protein-Coupled Receptors (GPCRs), including the angiotensin, endothelin, and vasopressin systems, are implicated in human preeclampsia (PreE) and animal models of the disorder. Cascade-specific termination of GPCR signaling following receptor activation is catalyzed by the Regulator of G protein Signaling (RGS) family members. Within the RGS B/R4 family, RGS5 and RGS2 are implicated in human PreE and gestational hypertensive disorders. Mutations within the RGS2 gene, a B/R4 RGS member, are associated with human hypertensive populations and increased risk of developing PreE and its sequelae. Given the role for the placenta ...


Identification Of Deubiquitinating Enzymes That Control The Cell Cycle In Saccharomyces Cerevisiae, Claudine E. Mapa Nov 2018

Identification Of Deubiquitinating Enzymes That Control The Cell Cycle In Saccharomyces Cerevisiae, Claudine E. Mapa

GSBS Dissertations and Theses

A large fraction of the proteome displays cell cycle-dependent expression, which is important for cells to accurately grow and divide. Cyclical protein expression requires protein degradation via the ubiquitin proteasome system (UPS), and several ubiquitin ligases (E3) have established roles in this regulation. Less is understood about the roles of deubiquitinating enzymes (DUB), which antagonize E3 activity. A few DUBs have been shown to interact with and deubiquitinate cell cycle-regulatory E3s and their protein substrates, suggesting DUBs play key roles in cell cycle control. However, in vitro studies and characterization of individual DUB deletion strains in yeast suggest that these ...


The Roles Of Primary Cilia In Cardiovascular Diseases, Rajasekharreddy Pala, Maha Jamal, Qamar Alshammari, Surya M. Nauli Nov 2018

The Roles Of Primary Cilia In Cardiovascular Diseases, Rajasekharreddy Pala, Maha Jamal, Qamar Alshammari, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are microtubule-based organelles found in most mammalian cell types. Cilia act as sensory organelles that transmit extracellular clues into intracellular signals for molecular and cellular responses. Biochemical and molecular defects in primary cilia are associated with a wide range of diseases, termed ciliopathies, with phenotypes ranging from polycystic kidney disease, liver disorders, mental retardation, and obesity to cardiovascular diseases. Primary cilia in vascular endothelia protrude into the lumen of blood vessels and function as molecular switches for calcium (Ca2+) and nitric oxide (NO) signaling. As mechanosensory organelles, endothelial cilia are involved in blood flow sensing. Dysfunction in endothelial ...


Genome-Wide Crispr Screens For Shiga Toxins And Ricin Reveal Golgi Proteins Critical For Glycosylation, Songhai Tian, Khaja Muneeruddin, Mei Yuk Choi, Liang Tao, Robiul H. Bhuiyan, Yuhsuke Ohmi, Keiko Furukawa, Koichi Furukawa, Sebastian Boland, Scott A. Shaffer, Rosalyn M. Adam, Min Dong Nov 2018

Genome-Wide Crispr Screens For Shiga Toxins And Ricin Reveal Golgi Proteins Critical For Glycosylation, Songhai Tian, Khaja Muneeruddin, Mei Yuk Choi, Liang Tao, Robiul H. Bhuiyan, Yuhsuke Ohmi, Keiko Furukawa, Koichi Furukawa, Sebastian Boland, Scott A. Shaffer, Rosalyn M. Adam, Min Dong

Open Access Articles

Glycosylation is a fundamental modification of proteins and membrane lipids. Toxins that utilize glycans as their receptors have served as powerful tools to identify key players in glycosylation processes. Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans. The Stxs screens identified major glycosyltransferases (GTs) and transporters involved in Gb3 biosynthesis, while the ricin screen identified GTs and transporters involved in N-linked ...


The Nf-Kappab Factor Relish Regulates Atg1 Expression And Controls Autophagy, Anubhab Nandy, Lin Lin, Panagiotis D. Velentzas, Louisa P. Wu, Eric H. Baehrecke, Neal S. Silverman Nov 2018

The Nf-Kappab Factor Relish Regulates Atg1 Expression And Controls Autophagy, Anubhab Nandy, Lin Lin, Panagiotis D. Velentzas, Louisa P. Wu, Eric H. Baehrecke, Neal S. Silverman

Open Access Articles

Macroautophagy and cell death both contribute to innate immunity, but little is known about how these processes integrate. Drosophila larval salivary glands require autophagy for developmentally programmed cell death, and innate immune signaling factors increase in these dying cells. Here, we show that the nuclear factor kappaB (NF-kappaB) factor Relish, a component of the immune deficiency (Imd) pathway, is required for salivary gland degradation. Surprisingly, of the classic Imd pathway components, only Relish and the PGRP receptors were involved in salivary gland degradation. Significantly, Relish controls salivary gland degradation by regulating autophagy but not caspases. In addition, expression of either ...


Fatty Acid Amides And Their Biosynthetic Enzymes Found In Insect Model Systems, Ryan L. Anderson Nov 2018

Fatty Acid Amides And Their Biosynthetic Enzymes Found In Insect Model Systems, Ryan L. Anderson

Graduate Theses and Dissertations

A fatty acid amide is precisely as the name suggests: A fatty acid (CHn-COOH), in which the hydroxyl group of the carboxylic acid is displaced by an amine functional group from a biogenic amine (R-NH2), ultimately forming an amide bond. Furthermore, these fatty acid amides can be composed of a variety of different acyl chain lengths donated by the fatty acid and a myriad of different biogenic amines. Thus, these molecules can be subdivided in a number of different ways including the separation of short chain (acetyl to heptanoyl) and long chain (palmitoyl to arachidonoyl) and also based off the ...


Investigating The Roles Of Fucosylation And Calcium Signaling In Melanoma Invasion, Tyler S. Keeley Nov 2018

Investigating The Roles Of Fucosylation And Calcium Signaling In Melanoma Invasion, Tyler S. Keeley

Graduate Theses and Dissertations

Melanoma is the deadliest form of skin cancer. Prognosis for early stage melanoma patients is excellent, and surgery is often curative for these patients. However, once patients have presented with invasive disease, the average 5-year survival rate drops significantly from over 90% to between 10 and 15%. Several therapies have been developed to target a commonly mutated oncogene BRAF, or its downstream effectors. Unfortunately, while these treatments show robust initial response, most patients relapse within a year. Moreover, therapy-resistant tumors are often more invasive and metastatic. Therefore, it is important to investigate the molecular mechanisms underlying melanoma invasion and metastasis ...


Colorectal Cancer Liver Metastatic Growth Depends On Pad4-Driven Citrullination Of The Extracellular Matrix, A. E. Yuzhalin, A. N. Gordon-Weeks, M. L. Tognoli, K. Jones, B. Markelc, R. Konietzny, R. Fischer, Aaron Muth, E. O'Neill, Paul R. Thompson, P. J. Venables, B. M. Kessler, S. Y. Lim, R. J. Muschel Nov 2018

Colorectal Cancer Liver Metastatic Growth Depends On Pad4-Driven Citrullination Of The Extracellular Matrix, A. E. Yuzhalin, A. N. Gordon-Weeks, M. L. Tognoli, K. Jones, B. Markelc, R. Konietzny, R. Fischer, Aaron Muth, E. O'Neill, Paul R. Thompson, P. J. Venables, B. M. Kessler, S. Y. Lim, R. J. Muschel

Open Access Articles

Citrullination of proteins, a post-translational conversion of arginine residues to citrulline, is recognized in rheumatoid arthritis, but largely undocumented in cancer. Here we show that citrullination of the extracellular matrix by cancer cell derived peptidylarginine deiminase 4 (PAD4) is essential for the growth of liver metastases from colorectal cancer (CRC). Using proteomics, we demonstrate that liver metastases exhibit higher levels of citrullination and PAD4 than unaffected liver, primary CRC or adjacent colonic mucosa. Functional significance for citrullination in metastatic growth is evident in murine models where inhibition of citrullination substantially reduces liver metastatic burden. Additionally, citrullination of a key matrix ...


Combined High-Speed Single Particle Tracking Of Membrane Proteins And Super-Resolution Of Membrane-Associated Structures, Hanieh Mazloom Farsibaf, Keith A. Lidke Nov 2018

Combined High-Speed Single Particle Tracking Of Membrane Proteins And Super-Resolution Of Membrane-Associated Structures, Hanieh Mazloom Farsibaf, Keith A. Lidke

Shared Knowledge Conference

Many experiments have shown that the diffusive motion of lipids and membrane proteins are slower on the cell surface than those in artificial lipid bilayers or blebs. One hypothesis that may partially explain this mystery is the effect of the cytoskeleton structures on the protein dynamics. A model proposed by Kusumi [1] is the Fence-Picket Model which describes the cell membrane as a set of compartment regions, each ~ 10 to 200 nm in size, created by direct or indirect interaction of lipids and proteins with actin filaments just below the membrane. To test this hypothesis, we have assembled a high-speed ...


The Dynamic Roles Of Mesenchymal Stem Cells In Colon Cancer, Shan Wang, Zhiguo Miao, Qiyuan Yang, Yimin Wang, Jinzhou Zhang Nov 2018

The Dynamic Roles Of Mesenchymal Stem Cells In Colon Cancer, Shan Wang, Zhiguo Miao, Qiyuan Yang, Yimin Wang, Jinzhou Zhang

Open Access Articles

Colon cancer is still one of the most common causes of cancer in human and is characterized by lymphocyte infiltrates and originates from the epithelial cells found in the lining of colon or rectum of the gastrointestinal tract. Mesenchymal stem cells (MSCs) are composed of the multipotent stem cell group of stroma and can be differentiated as various cell lineages, such as fibroblasts, osteoblasts, and adipocytes. MSCs provide mechanical and structural support and have potential functions during tumor growth and metastasis. The efficacy of MSC-based therapies is partly dependent on the migration and homing of MSCs to tumors and metastatic ...


Pyronaridine Exerts Potent Cytotoxicity On Human Breast And Hematological Cancer Cells Through Induction Of Apoptosis, Alberto Martinez, Paulina J. Villanueva, Sarah T. Baca, Rebecca E. Dejesus, Manuel Larragoity, Lisett Contreras, Denisse A. Gutierrez, Armando Varela-Ramirez, Renato J. Aguilera Nov 2018

Pyronaridine Exerts Potent Cytotoxicity On Human Breast And Hematological Cancer Cells Through Induction Of Apoptosis, Alberto Martinez, Paulina J. Villanueva, Sarah T. Baca, Rebecca E. Dejesus, Manuel Larragoity, Lisett Contreras, Denisse A. Gutierrez, Armando Varela-Ramirez, Renato J. Aguilera

Publications and Research

The potent antimalarial drug pyronaridine (PND) was tested for its potential as an anticancer drug. After exposing cancerous (17) and non-cancerous (2) cells to PND for 72 hr, PND was found to exhibit consistent and potent cytotoxic activity at low micromolar (μM) concentrations that ranged from 1.6 μM to 9.4 μM. Moreover, PND exerted a significant selective cytotoxicity index (SCI) on five out of seven breast cancer cell lines tested, with favorable values of 2.5 to 4.4, as compared with the non-cancerous breast MCF-10A cell line. By using the same comparison, PND exhibited a significant SCI ...


Thymic Epithelial Cell Reprogramming And Co-Culture With T-Cell Progenitors, Isabelle Riddle Nov 2018

Thymic Epithelial Cell Reprogramming And Co-Culture With T-Cell Progenitors, Isabelle Riddle

Georgia Undergraduate Research Conference (GURC)

The thymus is a lymphoid organ found in the neck region of vertebrates that produces T-cells critical for the adaptive immune system. However, thymus involution relatively early in the aging process leads to a deterioration in immune function. Models in regenerative medicine have the prospect of replacing lost cells and combating the problem. This experiment is a preliminary step geared towards achieving the overarching goal of boosting long-term maintenance of adaptive immunity over the typical aging process or following therapeutic immune depletion. Specifically, the objective is to show that disparate cell lineages can be reprogrammed—both morphologically and physiologically—using ...