Cell and Developmental Biology Commons^™

Targeting Wnt/Β-Catenin Pathway In Hepatocellular Carcinoma Treatment, Valery Vilchez, Lilia M. Turcios, Francesc Marti, Roberto Gedaly

Surgery Faculty Publications

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Liver cancer is generally related to hepatitis B or C infection and cirrhosis. Usually, patients with HCC are asymptomatic and are diagnosed at late stages when surgical treatment is no longer suitable. Limited treatment options for patients with advanced HCC are a major concern. Therefore, there is an urge for finding novel therapies to treat HCC. Liver cancer is highly heterogeneous and involved deregulation of several signaling pathways. Wnt/β-catenin pathway is frequently upregulated in HCC and it is implicated in maintenance of tumor initiating cells, drug …

Better Cognitive Control Of Emotional Information Is Associated With Reduced Pro-Inflammatory Cytokine Reactivity To Emotional Stress, Grant S. Shields, Shari Young Kuchenbecker, Sarah D. Pressman, Ken D. Sumida, George M. Slavich

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Stress is strongly associated with several mental and physical health problems that involve inflammation, including asthma, cardiovascular disease, certain types of cancer, and depression. It has been hypothesized that better cognitive control of emotional information may lead to reduced inflammatory reactivity to stress and thus better health, but to date no studies have examined whether differences in cognitive control predict pro-inflammatory cytokine responses to stress. To address this issue, we conducted a laboratory-based experimental study in which we randomly assigned healthy young-adult females to either an acute emotional stress (emotionally evocative video) or no-stress (control video) condition. Salivary levels of …

Long-Term Recovery From Acute Cold Shock In Caenorhabditis Elegans, Joseph D. Robinson, Jennifer R. Powell

Biology Faculty Publications

Background

Animals are exposed to a wide range of environmental stresses that can cause potentially fatal cellular damage. The ability to survive the period of stress as well as to repair any damage incurred is essential for fitness. Exposure to 2 °C for 24 h or longer is rapidly fatal to the nematode Caenorhabditis elegans, but the process of recovery from a shorter, initially non-lethal, cold shock is poorly understood.

Results

We report that cold shock of less than 12-hour duration does not initially kill C. elegans, but these worms experience a progression of devastating phenotypes over the …

Phlpp Negatively Regulates Cell Motility Through Inhibition Of Akt Activity And Integrin Expression In Pancreatic Cancer Cells, Alena J. Smith, Yang-An Wen, Payton D. Stevens, Jingpeng Liu, Chi Wang, Tianyan Gao

Markey Cancer Center Faculty Publications

Pancreatic adenocarcinoma is currently the fourth leading cause for cancer-related mortality. Malignant progression of pancreatic cancer depends not only on rapid proliferation of tumor cells but also on increased cell motility. In this study, we showed that increased PHLPP expression significantly reduced the rate of migration in pancreatic ductal adenocarcinoma (PDAC) cells whereas knockdown of PHLPP had the opposite effect. In addition, cell motility at the individual cell level was negatively regulated by PHLPP as determined using time-lapse imaging. Interestingly, the expression of β1 and β4 integrin proteins were decreased in PHLPP overexpressing cells and increased in PHLPP knockdown cells …

Mir-671-5p Inhibits Epithelial-To-Mesenchymal Transition By Downregulating Foxm1 Expression In Breast Cancer., Xiaohui Tan, Yebo Fu, Liang Chen, Woojin Lee, Yinglei Lai, M. Katayoon Rezaei, Sana Tabbara, Patricia Latham, Christine B Teal, Yan-Gao Man, Robert S. Siegel, Rachel F. Brem, Sidney W. Fu

Medicine Faculty Publications

MicroRNA (miRNA) dysfunction is associated with a variety of human diseases, including cancer. Our previous study showed that miR-671-5p was deregulated throughout breast cancer progression. Here, we report for the first time that miR-671-5p is a tumor-suppressor miRNA in breast tumorigenesis. We found that expression of miR-671-5p was decreased significantly in invasive ductal carcinoma (IDC) compared to normal in microdissected formalin-fixed, paraffin-embedded (FFPE) tissues. Forkhead Box M1 (FOXM1), an oncogenic transcription factor, was predicted as one of the direct targets of miR-671-5p, which was subsequently confirmed by luciferase assays. Forced expression of miR-671-5p in breast cancer cell lines downregulated FOXM1 …

Characterization Of Fluorescent Proteins For Three- And Four-Color Live-Cell Imaging In S. Cerevisiae, Ryo Higuchi-Sanabria, Enrique J. Garcia, Delia Tomoiaga, Emilia L. Munteanu, Paul Feinstein, Liza A. Pon

Publications and Research

Saccharomyces cerevisiae are widely used for imaging fluorescently tagged protein fusions. Fluorescent proteins can easily be inserted into yeast genes at their chromosomal locus, by homologous recombination, for expression of tagged proteins at endogenous levels. This is especially useful for incorporation of multiple fluorescent protein fusions into a single strain, which can be challenging in organisms where genetic manipulation is more complex. However, the availability of optimal fluorescent protein combinations for 3-color imaging is limited. Here, we have characterized a combination of fluorescent proteins, mTFP1/mCitrine/ mCherry for multicolor live cell imaging in S. cerevisiae. This combination can be used with …

Uncovering New Roles For The Aryl Hydrocarbon Receptor (Ahr) In Breast Cancer, Justin Kirk Tomblin

Theses, Dissertations and Capstones

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is responsive to many exogenous and endogenous ligands. AHR is of particular interest in cancer, and has been shown to play roles in tumor progression. As such, it has received growing attention as a possible chemotherapeutic target. Obesity increases the risk of breast cancer, complicates treatment of breast cancer, and stimulates the growth of larger, more aggressive mammary tumors. Many breast tumors in obese women are estrogen receptor (ER)-positive and, while targeting hormone receptors like ER is beneficial, many obese women see a recurrence of their cancer after standard …

Adult Neural Stem Cell Differentiation And Signaling Is Disrupted By Low-Level Silver Nanoparticle Exposure In Vitro, Robert Jefferson Cooper

Theses, Dissertations and Capstones

Silver nanoparticles (AgNP) are an emerging environmental contaminant with unique chemical and physical properties. They are utilized in products like medical dressings and children’s toys for their antimicrobial action. Though AgNP’s bioaccumulative nature and high-level toxicity are established, low-level effects from chronic exposure to AgNP-containing products and environmental AgNP remain unclear. This study uses adult neural stem cells, a model for neural cell function and neurodevelopment, to assess changes in cell differentiation and behavior following low-level AgNP exposure. In vitro, low-level AgNP produced dose- and timedependent formation of co-localized f-actin inclusions and β-catenin puncta. Neurite extension and arborization were also …

3,5-Dichloroaniline: Biotransformation And Mechanistic Aspects Of Nephrotoxicity In Vitro, Christopher Robert Racine

Theses, Dissertations and Capstones

Chlorinated anilines have been used as important chemical intermediates in the production of a wide variety of pharmaceutical, industrial, and agricultural products. Exposure to chloroanilines can arise in both occupational and environmental settings and can lead to toxicity to multiple organs, including the kidney. Previous studies have established that of the mono- and dichlorinated anilines, 3,5-dichloroaniline (3,5-DCA) possesses the most nephrotoxic potential both in vitro and in vivo. However, little is known concerning the role of renal metabolism in nephrotoxicity. The studies presented in the following dissertation are the first to explore the toxicity, metabolism, and bioactivation of 3,5-DCA in …

Single-Cell Mass Spectrometry For Discovery Proteomics: Quantifying Translational Cell Heterogeneity In The 16-Cell Frog (Xenopus) Embryo, Camille Lombard-Banek, Sally Ann Moody, Peter Nemes

Anatomy and Regenerative Biology Faculty Publications

We advance mass spectrometry from a cell population-averaging tool to one capable of quantifying the expression of diverse proteins in single embryonic cells. Our instrument combines capillary electrophoresis (CE), electrospray ionization, and a tribrid ultrahigh-resolution mass spectrometer (HRMS) to enable untargeted (discovery) proteomics with ca. 25 amol lower limit of detection. CE-μESI-HRMS enabled the identification of 500–800 nonredundant protein groups by measuring 20 ng, or <0.2% of the total protein content in single blastomeres that were isolated from the 16-cell frog (Xenopus laevis) embryo, amounting to a total of 1709 protein groups identified between n=3 biological replicates. By quantifying ≈150 nonredundant protein groups between all blastomeres and replicate measurements, we found significant translational cell heterogeneity along multiple axes of the embryo at this very early stage of development when the transcriptional program of the embryo has yet to begin.

Characterization Of The Three Zebrafish Orthologs Of The Mitochondrial Gtpase Miro/Rhot, Brittany M. Hollister, Kelsey A. Oonk, Douglas C. Weiser, Susan Walsh

Faculty Publications

Mitochondria exhibit dynamic locomotion and spatial rearrangement. This movement is necessary for a cell to maintain basic metabolic functions, and disruption of motility often results in cell death. Miro is a mitochondrial outer membrane Rho GTPase essential for mitochondrial movement and distribution in diverse systems, including yeast, animals, and plants. We sought to study the previously uncharacterized Miro protein family in zebrafish. We confirmed that, like human Miro, the zebrafish Miro proteins (Rhot1a, Rhot1b, and Rhot2) localize to mitochondria in mammalian tissue culture cells by both biochemical fractionation and immunofluorescent colocalization. In addition, using whole mount in situ hybridization, we …

Noninvasive Assessment Of Cardiac Abnormalities In Experimental Autoimmune Myocarditis By Magnetic Resonance Microscopy Imaging In The Mouse, Chandirasegaran Massilamany, Vahid Khalilzad-Sharghi, Arunakumar Gangaplara, David Steffen, Shadi F. Othman, Jay Reddy

Jay Reddy Publications

Myocarditis is an inflammation of the myocardium, but only ~10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-α 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-α 334-352 is shown. EAM and healthy mice …

Hexokinase Ii Localization Is Independent Of Ampk Activation In Hela Cells, Alyssa Brown

Graduate School of Biomedical Sciences Theses and Dissertations

In order for a cancer cell to thrive, it must alter its metabolism to produce the energy needed for rapid growth. Cells accomplish this by the Warburg Effect, or switching metabolism to aerobic glycolysis, where a cell can rapidly break down sugar into ATP, lactic acid and additional byproducts. Hexokinase 2, the enzyme that catalyzes the first committed step of glycolysis, may also be upregulated in cancer cells to increase glucose breakdown. Similar proteins for metabolism are found in both S. cerevisiae and mammalian cells. S. cerevisiae regulates metabolism through glucose repression, by Snf1 (mammalian homolog: AMPK) activation, which aids …

Utility And Origin Of Blood-Based Autoantibodies For Early Detection And Diagnosis Of Neurodegenerative Diseases, Cassandra Demarshall

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies are self-reactive antibodies that have been widely implicated as causal agents of autoimmune diseases. They are found in the blood of all human sera, regardless of age, gender, or the presence or absence of disease. While the underlying reason for their ubiquity remains unknown, it has been hypothesized that they participate in the clearance of blood-borne cell and tissue debris generated in both healthy and diseased individuals on a daily basis. Although much evidence supports this debris clearance role, recent studies also suggest a causal role for autoantibodies in disease. My thesis work has focused on this "cause and/or …

The Ecology And Evolution Of Rare, Soil Specialist Astragalus Plants In The Arid Western U.S., Joseph M. Statwick

Electronic Theses and Dissertations

Organisms that specialize in uncommon habitats are, by their very nature, inherently uncommon. Specialization has its advantages, namely reduced competition and predation, but it also incurs costs. Specialists often have small population sizes, narrow ranges, and fragmented habitat, all of which engender negative consequences on an evolutionary timescale. Herein, I examine benefits and costs of specialization in selenium-hyperaccumulating plants in the genus Astragalus (Fabaceae). These plants are disproportionately likely to be rare and of conservation concern. Thus, I optimized germination pretreatments for Astragalus species such that seed loss can be minimized during ex situ cultivation, and found that physical scarification …

Potential Role Of P21 Activated Kinase 1 (Pak1) In The Invasion And Motility Of Oral Cancer Cells., Muraleedharan Parvathy, Sreeharshan Sreeja, Rakesh Kumar, M. Radhakrishna Pillai

Biochemistry and Molecular Medicine Faculty Publications

Background

Oral cancer malignancy consists of uncontrolled division of cells primarily in and around the floor of the oral cavity, gingiva, oropharynx, lower lip and base of the tongue. According to GLOBOCAN 2012 report, oral cancer is one of the most common cancers among males and females in India. Even though significant advancements have been made in the field of oral cancer treatment modalities, the overall prognosis for the patients has not improved in the past few decades and hence, this demands a new thrust for the identification of novel therapeutic targets in oral cancer. p21 Activated Kinases (PAKs) are …

Mitosis In Circulating Tumor Cells Stratifies Highly Aggressive Breast Carcinomas., Daniel L. Adams, Diane K. Adams, Steingrimur Stefansson, Christian Haudenschild, Stuart S. Martin, Monica Charpentier, Saranya Chumsri, Massimo Cristofanilli, Cha-Mei Tang, R Katherine Alpaugh

Pathology Faculty Publications

BACKGROUND: Enumeration of circulating tumor cells (CTCs) isolated from the peripheral blood of breast cancer patients holds promise as a clinically relevant, minimally invasive diagnostic test. However, CTC utility has been limited as a prognostic indicator of survival by the inability to stratify patients beyond general enumeration. In comparison, histological biopsy examinations remain the standard method for confirming malignancy and grading malignant cells, allowing for cancer identification and then assessing patient cohorts for prognostic and predictive value. Typically, CTC identification relies on immunofluorescent staining assessed as absent/present, which is somewhat subjective and limited in its ability to characterize these cells. …

Examination Of Reticulocytosis Among Chronically Transfused Children With Sickle Cell Anemia., Megha Kaushal, Colleen Byrnes, Zarir Khademian, Natalie Duncan, Naomi L.C. Luban, Jeffery L Miller, Ross M. Fasano, Emily Riehm Meier

Pediatrics Faculty Publications

Sickle cell anemia (SCA) is an inherited hemolytic anemia with compensatory reticulocytosis. Recent studies have shown that increased levels of reticulocytosis during infancy are associated with increased hospitalizations for SCA sequelae as well as cerebrovascular pathologies. In this study, absolute reticulocyte counts (ARC) measured prior to transfusion were analysed among a cohort of 29 pediatric SCA patients receiving chronic transfusion therapy (CTT) for primary and secondary stroke prevention. A cross-sectional flow cytometric analysis of the reticulocyte phenotype was also performed. Mean duration of CTT was 3.1 ± 2.6 years. Fifteen subjects with magnetic resonance angiography (MRA) -vasculopathy had significantly higher …

Functional Analysis Of Rpl22: Coordinating Differentiation Signals And Developmental Gene Translation To Promote Cell Fate Decisions, Stephen Kim

Graduate School of Biomedical Sciences Theses and Dissertations

The execution of meiosis and spore formation in S. cerevisiae requires a transient transcription program that is initiated by Ime I-dependent destruction of the repressor Ume6. IMEJ transcription is tightly contro1led by both cell type and nutritional cues but how its translation is regulated has been unknown. This study demonstrates that Rpl22A and Rpl22B, eukaryotic-specific ribosomal protein paralogs of the 60S large subunit, are required for efficient Ime I translation. While IME1 mRNA is induced normally in the absence of both para logs following transfer to sporulation medium, Ume6 remains stabilized, downstream early meiotic gene remain repressed, and development is …

The Role Of Cyclic Nucleotide Gated Channels, Retrograde Ift Rate Change, And Chemical Concentration In The Olfactory Habituation Of C. Elegans, Michaela A. O'Driscoll

Honors Program Theses

The cilium is an organelle utilized by the cell for signaling purposes. Olfaction is a process that utilizes cilia for cell signaling, specifically as the starting point of the neuronal olfactory pathway, by which volatile odorant molecules trigger neuronal depolarization and subsequent behavioral modification. Related to cilia function and development is the process of intraflagellar transport (IFT): the bidirectional movement of channels, receptors, and other proteins by motors along the microtubules of the cilia, including odorant receptors. The phenomenon of odorant habituation upon continuous exposure to an attractant chemical has been previously confirmed, but the role of IFT in this …