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Full-Text Articles in Cell Biology

Invitro-Q: A High-Throughput Biosensor Used To Evaluate The Mechanism Of Phagocytosis Of Macrophages Using Different Particles, Marynawal Abdou, Abiche H. Dewilde May 2017

Invitro-Q: A High-Throughput Biosensor Used To Evaluate The Mechanism Of Phagocytosis Of Macrophages Using Different Particles, Marynawal Abdou, Abiche H. Dewilde

UMass Center for Clinical and Translational Science Research Retreat

The method of phagocytosis of a particle can provide information on how macrophages respond to a detected particle. The response elicited varies based on the nature of the particle and in turn changes which receptor-mediated phagocytosis is initiated. We have developed a multi-well cell-based sensor that can monitor real-time biological changes in living cells, such as mass redistribution, and viscoelasticity. This system provides unique kinetic information regarding the phenotypic change in the cells post treatment. As a proof of principle study, we evaluate macrophage phagocytosis using three different particles: latex beads, Zymosan A, and Staphylococcus aureus. These studies show the ...


Broad Repertoire Of T Cell Autoreactivity Directly From Islets Of Donors With Type 1 Diabetes (T1d), Jenny Aurielle B. Babon, Megan E. Denicola, David M. Blodgett, Inne Crevecoeur, Thomas S. Buttrick, Rene Maehr, Rita Bottino, Ali Naji, John Kaddis, Wassim Elyaman, Eddie A. James, Rachana Haliyur, Marcela Brissova, Lut Overburgh, Chantal Mathieu, Thomas Delong, Kathryn Haskins, Alberto Pugliese, Martha Campbell-Thompson, Clayton Mathews, Mark A. Atkinson, Alvin C. Powers, David Harlan, Sally C. Kent May 2017

Broad Repertoire Of T Cell Autoreactivity Directly From Islets Of Donors With Type 1 Diabetes (T1d), Jenny Aurielle B. Babon, Megan E. Denicola, David M. Blodgett, Inne Crevecoeur, Thomas S. Buttrick, Rene Maehr, Rita Bottino, Ali Naji, John Kaddis, Wassim Elyaman, Eddie A. James, Rachana Haliyur, Marcela Brissova, Lut Overburgh, Chantal Mathieu, Thomas Delong, Kathryn Haskins, Alberto Pugliese, Martha Campbell-Thompson, Clayton Mathews, Mark A. Atkinson, Alvin C. Powers, David Harlan, Sally C. Kent

UMass Center for Clinical and Translational Science Research Retreat

Type 1 diabetes (T1D) is an autoimmune disease characterized by the infiltration of lymphocytes into the insulin-producing β-cells in the pancreas. We have isolated live T cells sorted or grown directly from the isolated, handpicked islets of human donors with T1D. We received ~500 islet equivalent EQ of variable purity (10-90%) from 12 donors with T1D (disease duration 0.42-20 years) and from seven control donors and two donors with type 2 diabetes (T2D). A total of 321 T cell lines and clones were derived from the islets of donors with T1D (3 lines from the 9 control donors). These ...


C1qbp Inhibits Dux4-Dependent Gene Activation And Can Be Targeted With 4mu, Alec M. Desimone, Genila Bibat, Kathryn Wagner, Guido Stadler, Woodring E. Wright, John D. Leszyk, Charles P. Emerson Jr. May 2017

C1qbp Inhibits Dux4-Dependent Gene Activation And Can Be Targeted With 4mu, Alec M. Desimone, Genila Bibat, Kathryn Wagner, Guido Stadler, Woodring E. Wright, John D. Leszyk, Charles P. Emerson Jr.

UMass Center for Clinical and Translational Science Research Retreat

FSHD is linked to the misexpression of the DUX4 gene contained within the D4Z4 repeat array on chromosome 4. The gene encodes the DUX4 protein, a cytotoxic transcription factor that presumably causes the symptoms of the disease. However, individuals have been identified who express DUX4 in their muscle biopsies, but who remain asymptomatic, suggesting that there are other factors that modify FSHD penetrance or severity. We hypothesized that an FSHD-modifying factor would physically interact with DUX4, and we took a proteomic approach to identify DUX4-interacting proteins. We identified the multifunctional C1QBP protein as one such factor. C1QBP is known to ...


Optimizing Microfluidic Design For Cell Separation, Joseph Wakim, Marisel De Jesus Vega, Nese Orbey, Carol Barry May 2017

Optimizing Microfluidic Design For Cell Separation, Joseph Wakim, Marisel De Jesus Vega, Nese Orbey, Carol Barry

UMass Center for Clinical and Translational Science Research Retreat

To evaluate the performance of various designs of crossflow filtration microfluidic devices, blood flow was modeled using computational fluid dynamics software (COMSOL Multiphysics). Velocity profiles were generated and used to analyze four critical design parameters: pillar size, pillar shape, gap size, and wall length. These parameters were optimized to yield greatest flow from an unfiltered main channel into two filtered side channels of the device, thereby maximizing filtration capacity.

Devices containing pillars of 10 µm diameter yielded a significantly greater filtration capacity than devices with pillars of 20 µm diameter. Flow patterns from the main channel to the side channels ...


Microengineering Approaches For Regenerative Medicine, Yubing Sun May 2016

Microengineering Approaches For Regenerative Medicine, Yubing Sun

UMass Center for Clinical and Translational Science Research Retreat

Stem cells, especially human pluripotent stem cells (hPSCs), hold significant promise for modeling developmental and disease processes, drug and toxicology screening, and cell-based regenerative medicine. Most hPSC studies have so far focused on identifying extrinsic soluble factors, intracellular signaling pathways, and transcriptional regulatory networks involved in regulating hPSC behaviors. We focus on the development and applications of some novel synthetic micromechanical systems to understand the mechano-sensitive and -responsive properties of hPSCs and their functional regulation of self-renewal, directed differentiation, and survival of hPSCs. First, we have demonstrated that rigid PDMS micropost arrays (PMAs) support the maintenance of pluripotency of hPSCs ...


Activin Limits Progenitor Capability By Promoting Epithelial Cell Differentiation In The Mammary Gland, Karen A. Dunphy, Thiruppavai Chandrasekaran, Niraj Bhatt, Michelle Chen, Amy L. Roberts, Mary Hagen, D. Joseph Jerry May 2014

Activin Limits Progenitor Capability By Promoting Epithelial Cell Differentiation In The Mammary Gland, Karen A. Dunphy, Thiruppavai Chandrasekaran, Niraj Bhatt, Michelle Chen, Amy L. Roberts, Mary Hagen, D. Joseph Jerry

UMass Center for Clinical and Translational Science Research Retreat

Transforming growth factor beta (TGF-beta) and activin utilize common signaling pathways, via smad2/3 and smad4, to mediate tumor suppression by effecting cell cycle arrest and apoptosis. Differences in temporal expression patterns suggest that each cytokine has specific roles in mammary gland development. Activin is expressed during pregnancy and lactation and is required for branching and lactogenesis, implying a role in mammary gland maturation. In contrast, TGF-beta is expressed during involution during mammary gland regression and functions to re-organize the mammary epithelial content to the non-lactating state. Previously, we found that TGF-beta and activin do share common signaling pathways allowing ...


High Performance Amphiphilic Polymer/Hydroxyapatite Composite Tissue Scaffolds, Artem B. Kutikov, Jie Song May 2014

High Performance Amphiphilic Polymer/Hydroxyapatite Composite Tissue Scaffolds, Artem B. Kutikov, Jie Song

UMass Center for Clinical and Translational Science Research Retreat

There is a critical clinical need for alternatives to autograft and allograft bone for over 500,000 bone grafting operations performed each year in the United States. Current synthetic bone grafts suffer from poor handling characteristics, brittle mechanical properties, and inconsistent bioactivity. By blending a biodegradable amphiphilic polymer with hydroxyapatite (HA), the main mineral component in bone, we developed an improved synthetic bone graft. The polymer/HA composites were fabricated in both 2-D and 3-D forms by electrospinning and 3-D printing. These materials exhibited unique handling characteristics such as high tensile elasticity (>200% failure strain) and self-stiffening properties upon hydration ...


Pericyte Nf-Κb Activation Enhances Endothelial Cell Proliferation And Proangiogenic Cytokine Secretion, Katherine E. Labarbera, Robert D. Hyldahl, Sarah Witkowski May 2014

Pericyte Nf-Κb Activation Enhances Endothelial Cell Proliferation And Proangiogenic Cytokine Secretion, Katherine E. Labarbera, Robert D. Hyldahl, Sarah Witkowski

UMass Center for Clinical and Translational Science Research Retreat

Pericytes are skeletal muscle resident, multipotent stem cells that are localized to capillaries. They respond to damage through activation of nuclear-factor kappa-B (NF-κB), a transcription factor that regulates many cellular processes including inflammation. Research has shown that pericyte NF-κB activation positively affects myoblast proliferation. It is unknown how pericyte NF-κB affects signaling and proliferation of endothelial cells, an important component of muscle tissue microcirculation.

PURPOSE: To determine the effects of altered pericyte NF-κB activity on endothelial cell proliferation and identify inflammatory factors involved in this cell-cell signaling.

METHODS: Human primary pericytes were transfected with vectors designed to increase or decrease ...


Exosome-Mediated Delivery Of Rna Interference And Mirna Mimic, Fatemeh Momen-Heravi, Shashi Bala, Terence N. Bukong, Gyongyi Szabo May 2014

Exosome-Mediated Delivery Of Rna Interference And Mirna Mimic, Fatemeh Momen-Heravi, Shashi Bala, Terence N. Bukong, Gyongyi Szabo

UMass Center for Clinical and Translational Science Research Retreat

Exosomes, membranous nanovesicles, naturally carry bio-macromolecules and play pivotal roles in both physiological intercellular crosstalk and disease pathogenesis. Here, we showed that B cell-derived exosomes can function as vehicles to deliver exogenous miRNA-155 mimic or inhibitor into hepatocytes or macrophages, respectively. Stimulation of B cells significantly increased exosome production. Unlike in parental cells, baseline level of miRNA-155 was very low in exosomes derived from stimulated B cells. Exosomes loaded with a miRNA-155 mimic significantly increased miRNA-155 levels in primary mouse hepatocytes and the liver of miRNA-155 knockout mice. Treatment of RAW macrophages with miRNA-155 inhibitor loaded exosomes resulted in statistically ...


Anti-Ppkcθ (T538) Delivery Via Cell Penetrating Peptide Mimics As A Novel Treatment Of Aplastic Anemia, Emrah Ilker Ozay, Gabriela Gonzalez-Perez, Joe Torres, Gregory N. Tew, Lisa M. Minter May 2014

Anti-Ppkcθ (T538) Delivery Via Cell Penetrating Peptide Mimics As A Novel Treatment Of Aplastic Anemia, Emrah Ilker Ozay, Gabriela Gonzalez-Perez, Joe Torres, Gregory N. Tew, Lisa M. Minter

UMass Center for Clinical and Translational Science Research Retreat

The objective of this study is to deliver anti-pPKCθ (T538) into T cells (hPBMCs) by using cell penetrating peptide mimics (CPPMs) to neutralize PKCθ activity both in vitro and in vivo, with the eventual goal of treating aplastic anemia (AA). AA is an immune-mediated bone marrow failure disease caused by T helper type 1 (Th1) autoimmune responses, which destroy blood cell progenitors. It was previously reported that protein kinase C theta (PKCθ), expressed specifically in T cells, plays an important role in T cell signaling by mediating Th1 differentiation. Mice treated with Rottlerin, a pharmacological inhibitor of PKCθ, are rescued ...


Multiple Approaches To Determine Toxicity Of Micro And Nano-Sized Titanium Dioxide Materials When Exposed To Human Red Blood Cells, Aaron Stella, Shu-Feng Hsieh, Dhimiter Bello, Daniel Schmidt, Eugene Rodgers May 2014

Multiple Approaches To Determine Toxicity Of Micro And Nano-Sized Titanium Dioxide Materials When Exposed To Human Red Blood Cells, Aaron Stella, Shu-Feng Hsieh, Dhimiter Bello, Daniel Schmidt, Eugene Rodgers

UMass Center for Clinical and Translational Science Research Retreat

Introduction: The utility of engineered nanomaterials’ is growing, particularly the titanium dioxide (TiO2) polymorphs. TiO2 is very useful for brightening paints, and coloring foods. Nano-sized TiO2 is also useful for sunscreens, cosmetics, and can be utilized as a photocatalyst. However, the nanometer size and the large specific surface area of the TiO2 materials are physicochemical characteristics which may contribute to human red blood cell (RBC) damage. Using RBCs as a cellular model, we have evaluated the effects of TiO2 nanoparticle exposure to RBCs by quantifying oxidized glutathione, oxidized membrane vitamin E, hemolysis, hemoglobin adsorption, and cellular aggregation. Results: Red blood ...


Transdifferentiation Of Α- To Β-Cells Is Enhanced In Fstl3 Ko Mice, Alan Schneyer, Danielle Andrzejewski, Amy Burnside, Melissa Brown May 2014

Transdifferentiation Of Α- To Β-Cells Is Enhanced In Fstl3 Ko Mice, Alan Schneyer, Danielle Andrzejewski, Amy Burnside, Melissa Brown

UMass Center for Clinical and Translational Science Research Retreat

Both type 1 and type 2 diabetes involve loss of functional pancreatic B-cells which is driving research into potential replacement sources. Expansion of functional B-cell mass, such as through induction of B-cell neogenesis or through transdifferentiation of A-cells into functional B-cells represent appealing therapeutic solutions to restoring glucose control. To date, however, these processes have been induced through genetic manipulation or severe pancreatic injury. It remains to be determined whether transdifferentiation or neogenesis contribute to functional B-cell mass under normal physiological conditions and/or contribute to B-cell expansion and how these processes are regulated.

We have reported that inactivation of ...


Molecular Mechanisms Of Fsh Muscular Dystrophy Pathogenesis, Peter L. Jones, Takako I. Jones May 2013

Molecular Mechanisms Of Fsh Muscular Dystrophy Pathogenesis, Peter L. Jones, Takako I. Jones

UMass Center for Clinical and Translational Science Research Retreat

Discussion of a new research initiative at UMass Medical School focused on the pathogenesis of Facioscapulohumeral Muscular Dystrophy (FSHD) and efforts towards diagnostics and therapeutics. This presentation is part of the retreat mini-symposium entitled: Neuromuscular Diseases: Pathogenesis and the Road to Therapeutics.


Dux4 Target Gene Expression In Mouse Muscle Transplanted With Muscle Cells From Fshd Patients, James A. Windelborn, Charles P. Emerson, Jr. May 2013

Dux4 Target Gene Expression In Mouse Muscle Transplanted With Muscle Cells From Fshd Patients, James A. Windelborn, Charles P. Emerson, Jr.

UMass Center for Clinical and Translational Science Research Retreat

Facioscapulohumeral Muscular Dystrophy (FSHD) is one of the most prevalent forms of muscular dystrophy. However, because of the unique nature of the genetic abnormality underlying the disease, there is currently no widely available laboratory model. In order to gain insights into FSHD molecular pathology, we developed a xenograft model by transplanting myogenic cells from patients with FSHD (4qA contractions) as well as from their unaffected relatives into the tibialis anterior muscles of immunodeficient mice. Our findings show that muscle xenografts derived from FSHD myogenic cells express Dux4 target genes, recapitulating the expression of these disease biomarkers in muscle biopsies of ...


Activation Of The Epidermal Growth Factor Receptor (Egrf) Is Required For Cxcl12 Mediated Erk And Akt Signaling During Prostate Myofibroblast Phenoconversion, Jose A. Rodriguez-Nieves, Jill A. Macoska May 2013

Activation Of The Epidermal Growth Factor Receptor (Egrf) Is Required For Cxcl12 Mediated Erk And Akt Signaling During Prostate Myofibroblast Phenoconversion, Jose A. Rodriguez-Nieves, Jill A. Macoska

UMass Center for Clinical and Translational Science Research Retreat

Benign prostate hyperplasia (BPH), a condition of the prostate common in aging in men, is associated with urinary voiding dysfunction, or Lower Urinary Tract Symptoms (LUTS). Although inflammation and abnormal muscle contraction are known to be key players in the development of LUTS, tissue fibrosis may also be an important and previously unrecognized contributing factor. Tissue fibrosis arises from the differentiation of fibroblasts into myofibroblasts, which produce and secrete collagens and fibronectins that remodel the extracellular matrix (ECM). This differentiation process is usually accomplished by activation of the TGF-β/TGFβRII axis. However, in this study we report that the CXC-type ...


Obesity-Induced Diabetes And Lower Urinary Tract Fibrosis Promote Urinary Voiding Dysfunction In A Mouse Model, Mehrnaz Gharaee−Kermani, Jose A. Rodriguez-Nieves, Jill A. Macoska May 2013

Obesity-Induced Diabetes And Lower Urinary Tract Fibrosis Promote Urinary Voiding Dysfunction In A Mouse Model, Mehrnaz Gharaee−Kermani, Jose A. Rodriguez-Nieves, Jill A. Macoska

UMass Center for Clinical and Translational Science Research Retreat

Background: Progressive aging- and inflammation-associated fibrosis effectively remodels the extracellular matrix to increase prostate tissue stiffness and reduce urethral flexibility, resulting in urinary flow obstruction and Lower Urinary Tract Symptoms (LUTS). In the current study we sought to test whether senescence-accelerated mouse prone (SAMP)6 mice, which were reported to develop prostatic fibrosis, would also develop LUTS, and whether these symptoms would be exacerbated by diet-induced obesity and concurrent Type 2 Diabetes Mellitus (T2DM).

Methods: To accomplish this, SAMP6 and AKR/J background strain mice were fed regular mouse chow, low fat diet chow, or high fat diet chow for ...


Cxcl-Type Chemokines−Induced Fibrosis In The Lower Urinary Tract, Mehrnaz Gharaee−Kermani, Jill A. Macoska May 2013

Cxcl-Type Chemokines−Induced Fibrosis In The Lower Urinary Tract, Mehrnaz Gharaee−Kermani, Jill A. Macoska

UMass Center for Clinical and Translational Science Research Retreat

No abstract provided.


Estrogen Receptor Beta Selectively Restricts Proliferation And Favors Surveillance In Mammary Epithelial Cells, Karen A. Dunphy, Erick Roman-Perez, Rehaneh Hooshyar, Mary J. Hagen, Amy L. Roberts, Mara Isel Guerrero-Zayas, D. Joseph Jerry May 2013

Estrogen Receptor Beta Selectively Restricts Proliferation And Favors Surveillance In Mammary Epithelial Cells, Karen A. Dunphy, Erick Roman-Perez, Rehaneh Hooshyar, Mary J. Hagen, Amy L. Roberts, Mara Isel Guerrero-Zayas, D. Joseph Jerry

UMass Center for Clinical and Translational Science Research Retreat

Estrogen (17β-estradiol) has paradoxical effects in both promoting and preventing breast cancer as estrogen activates proliferation, but also promotes p53-mediated surveillance pathways. Estrogen mediates its effects in target tissues through the activation of estrogen receptor subtypes: ERα and ERβ. To examine the capability of these receptors in mediating surveillance as opposed to proliferation, selective estrogen receptor agonists were compared with 17β-estradiol for induction of proliferation and radiation induced apoptosis in vivo. Transcriptional regulation of estrogen-responsive genes was also compared in mouse mammary epithelium in vivo and in the human mammary MCF7 cell line transduced with a repressible ERβ. Selective activation ...