Digital Commons Network^™

Bioengineering In Vitro Human Trabecular Meshwork Models For Glaucoma Therapeutic Screening, Karen Yud Torrejon

Legacy Theses & Dissertations (2009 - 2024)

Glaucoma refers to a group of slowly progressing eye disorders that lead to damage to the optic nerve, resulting in irreversible vision loss. Recent statistics by the World Health Organization places glaucoma as a leading cause of blindness worldwide, affecting nearly 80 million people. Lowering intraocular pressure (IOP) is currently the only effective target for therapeutic intervention in glaucoma. IOP is mostly controlled by the outflow of the aqueous humor (AH) through the trabecular meshwork (TM). The TM and adjacent endothelium of Schlemm’s canal, known as the conventional outflow-tract, control AH outflow and thus determine IOP.

Joint Attention Intervention With Assisting Parent­ Mediated Techniques To Increase A Toddler With Autism Spectrum Disorders' Use Of Joint Attention: A Single Case Study, Rebecca Schulz

All Graduate Theses, Dissertations, and Other Capstone Projects

Attention Intervention (JAI) conducted by graduate researcher, parent, and caregiver, would change the use of joint attention (JA) by a three-year-old suspected of having Autism Spectrum Disorder (ASD). The participant was a three-­year-­old child suspected of having ASD. Intervention was conducted twice per week for 30-45 minute duration by the student graduate researcher at a university clinic under the supervisor of Dr. Bonnie Berg, CCC­SLP. The parent and child's caregiver were trained in JAI and implemented the intervention daily in the home environment. The author's research question was, "Will the use of a JAI parent­mediated intervention model increase the JA …

Extensive And Persistent Disruption Of Neurovascular Coupling By A Single Cerebral Microinfarct, Philipp Mcconnell Summers

MUSC Theses and Dissertations

Cerebral microinfarcts (CMI), microscopic brain lesions caused by blockade of small blood vessels, have recently emerged as a potential determinant of cognitive decline. Though small in size, our recent work demonstrated that a single, strategically placed CMI was sufficient to disrupt sensory input in a behavioral task. However, the means by which such small lesions disrupt brain function remain poorly understood. We imaged vascular function in awake, head-fixed mice using two-photon microscopy to examine the impact of CMI on neurovascular coupling. CMI were generated in cortex by photothrombotic occlusion of single penetrating vessels through a thinned-skull cranial window. Vibrissa-evoked dilation …

Coffee: A Selected Overview Of Beneficial Or Harmful Effects On The Cardiovascular System?, Thomas F. Whayne Jr.

Internal Medicine Faculty Publications

With a history that began in 800 A.D., coffee is the most popular drink known and as a result, the issues regarding its physiologic effects deserve attention. Maintaining alertness is a well-known benefit and in addition, the cardiovascular (CV) effects of the active compounds, which include polyphenols and caffeine, must be considered. Genetics are relevant and where slow caffeine metabolism is inherent, the risk of nonfatal myocardial (MI) has been shown to be increased. Overall risk for coronary heart disease (CHD) is not supported and unless there is excessive intake, congestive heart failure (CHF) is not adversely affected; in moderation, …

Hiv And Minority Youth, Mandakini Sadhir, Hatim A. Omar

Pediatrics Faculty Publications

Human Immunodeficiency virus (HIV) infection is a major public health problem with the burden of disease increasing in adolescents and young adults particularly among black males and males who have sex with males (MSM).

Paper I: Stress In Adolescents, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

It is well known that adolescents experience stress. In this article, sources of adolescent stress will be discussed as well as the physiological effects of stress on the body. Stress disorders will also be briefly reviewed. Mainly, research on stress management strategies that have been evaluated in adolescents will be presented. Many studies have a small number of participants and lack control groups. Therefore, there is a need for ongoing research in this important area.

Part Ii - Stress And Stress Management Strategies In Adolescents, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

It is well known that adolescents experience stress. In this article, sources of adolescent stress will be discussed as well as the physiological effects of stress on the body. Stress disorders will also be briefly reviewed. Mainly, research on stress management strategies that have been evaluated in adolescents will be presented. Many studies have a small number of participants and lack control groups. Therefore, there is a need for ongoing research in this important area.

Diabetes Phenotypes In Transgenic Pancreatic Cancer Mouse Models, Toya Albury-Warren

Electronic Theses and Dissertations

Protein Kinase B/AKT, a serine/threonine kinase with three isoforms (AKT1-3), is downstream of phosphatidylinositol 3-kinase (PI3K), and signals through the phosphorylation and subsequent activation or inhibition of downstream substrates, such as mammalian target of rapamycin complex 1 (mTORC1) or glycogen synthase kinase 3 beta (GSK-3?), respectively. The AKT1 isoform is predominantly recognized for regulation of cell survival, growth, and proliferation, due to its constitutive activation in pancreatic cancers (e.g., islet cell carcinoma and pancreatic adenocarcinoma). The progression of pancreatic ductal adenocarcinoma (PDAC), the most lethal common cancer, is initiated by activation mutations of the KRas oncogene. This leads to additional …

Challenges And Opportunities For Implementing Evidence-Based Antenatal Care In Mozambique: A Qualitative Study, Adriano Biza, Ingeborg Jille-Traas, Mercedes Colomar, Maria Belizan, Jennifer Requejo Harris, Beatrice Crahay, Mario Merialdi, My Huong Nguyen, Fernando Althabe, Alicia Aleman, Eduardo Berge, Alicia Carbonell, Leonardo Chavane, Therese Delvaux, Diederike Geelhoed, Metin Gülmezoglu, Celsa Regina Malapende, Armando Melo, Nafissa Bique Osman, Mariana Widmer, Marleen Temmerman, Ana Pilar Betrán

Obstetrics and Gynaecology, East Africa

Background: Maternal mortality remains a daunting problem in Mozambique and many other low-resource countries. High quality antenatal care (ANC) services can improve maternal and newborn health outcomes and increase the likelihood that women will seek skilled delivery care. This study explores the factors influencing provider uptake of the recommended package of ANC interventions in Mozambique.

Methods: This study used qualitative research methods including key informant interviews with stakeholders from the health sector and a total of five focus group discussions with women with experience with ANC or women from the community. Study participants were selected from three health centers located …

Targeting The Tight Junction Protein, Zonula Occludens-1, With The Connexin 43 Mimetic Peptide, Αct-1 Reduces Vegf-Dependent Rpe Pathophysiology, Elizabeth Christa Obert

MUSC Theses and Dissertations

Age-related macular degeneration (AMD) is a multifactorial disease and is regarded as the predominant cause of central vision loss in the elderly in industrialized countries. A critical target tissue in AMD is the retinal pigment epithelium (RPE), which together with Bruch’s membrane forms the outer blood-retina barrier (BRB). RPE-barrier dysfunction in AMD might result from attenuation and disruption of intercellular tight junctions. Zonula occludens-1 (ZO-1) is a major structural protein of intercellular junctions. A connexin-based peptide mimetic, αCT-1 (Alpha Connexin carboxy-Terminal 1), was developed which competitively inhibits ZO-1 interaction with its binding partners. We hypothesized that targeting ZO-1 signaling using …

Mechanisms Of Mitochondrial Dysfunction In Sepsis-Induced Kidney Injury, Joshua Andrew Smith

MUSC Theses and Dissertations

Mitochondrial dysfunction is a well-characterized pathophysiological feature of acute kidney injury (AKI). Our laboratory has previously implicated suppression of mitochondrial biogenesis, the process by which cells generate new and functional mitochondria, as an important contributor to development of mitochondrial dysfunction in multiple experimental models of AKI. However, relatively little is known about the molecular mechanisms responsible for disruption of biogenesis in renal cells. The primary goals of this project were to define signaling pathways mediating acute suppression of renal cortical mitochondrial biogenesis and to characterize changes in glycolytic metabolism that might support both cellular and organ function following sepsis-induced AKI. …

The Role Of The Complement System In Cigarette Smoke Induced Emphysema Development And Progression, Sarah E. Stephenson

MUSC Theses and Dissertations

Emphysema is a complex inflammatory condition of the respiratory tract with an incompletely elucidated pathogenesis. Due to the complexity of the disease, treatment options are limited for patients and have poor efficacy. Therefore a greater understanding of disease pathogenesis is imperative to expand therapeutic strategies. Central to disease development is the activation of the innate and adaptive immune system, however, targeting blockade of only one side of the immune response, has shown little clinical benefit. The complement system, while regarded as an innate immune mechanism, can modulate both innate and adaptive immune responses. Given these dual modulatory effects, the complement …

A Therapeutic Approach For Senile Dementias: Neuroangiogenesis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Alzheimer's disease (AD) and related senile dementias (SDs) represent a growing medical and economic crisis in this country. Apart from cautioning persons about risk factors, no practical, effective therapy is currently available. Much of the recent research in AD has been based on the amyloid cascade theory. Another approach assumes a vascular basis for SDs. This paper presents evidence from a score of studies that cerebral capillary density (CCD) declines during old age in animals and people as well as in AD. Neuroangiogenic (NAG) factors initiate and maintain capillaries in the brain. Thus a waning level of these factors and …

Comprendre Les Grossesses Non Désirées Au Sénégal : Rapport Du Profil Pays [Compte Rendu De L’Atelier De Dissémination Des Résultats Auprès Des Parlementaires], Babacar Mane, Bocar Mamadou Daff, Marie-Jesus Buabey, Abdelylah Lakssir

Reproductive Health

En partenariat avec le Ministère de la Santé et de l'Action Sociale et l’initiative Partners in Population and Development, le bureau du Population Council—Sénégal a organisé une rencontre avec des membres de l’Assemblée Nationale et d’autres acteurs locaux clés pour diffuser les résultats du rapport de l’étude sur le profil pays menée dans le cadre du projet de recherche "Strengthening Evidence for Programming on Unintended Pregnancy” plus connu sous l’acronyme “STEP UP.” A l’issue de la réunion, les recommandations ont été formulées concernant la législation, le renforcement des capacités et la prise en charge des problèmes de santé de la …

The Feasibility Of Implementing A Novel Electrical Stimulation Device In The Self-Management Of Hand Burn Pain, Katrina Liddiard

Theses : Honours

Burns are widely acknowledged as one of the most painful injuries experienced, and poorly controlled pain following burn injury has been linked to reduced psychological adjustment, lower quality of life, and increased risk of developing a chronic pain state. Transcutaneous electrical nerve stimulation has been used for pain relief in a range of medical conditions, and may have the potential to reduce pain and analgesic consumption for burns patients. The burn care environment presents unique challenges to the introduction of new interventions, and the feasibility of introducing a novel form of electrical stimulation into this environment has not been tested. …

The Association Between Environmental Cadmium Exposure And All-Cause Mortality And Cardiovascular Disease In A Cohort Of Elderly Western Australian Women, Kane Deering

Theses : Honours

Introduction: Recent research suggests an association between environmental cadmium exposure and increased risk of, and death from, cardiovascular disease, the number one cause of mortality in Australia and worldwide. However, the research to date is neither comprehensive nor have there been any studies conducted on an Australian population. This study identified whether increasing concentrations of urinary cadmium in elderly West Australian women was associated with an increased odds of incidence of, and deaths from CVD, as well as all-cause mortality.

Method: Cadmium excretion was measured in urine samples collected at baseline (1998) from 1359 women from Perth who …

Ethanol At Low Concentrations Protects Glomerular Podocytes Through Alcohol Dehydrogenase And 20-Hete., Ellen T. Mccarthy, Jianping Zhou, Ryan Eckert, David Genochio, Rishi Sharma, Olurinde Oni, Alok De, Tarak Srivastava, Ram Sharma, Virginia J. Savin, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

Clinical studies suggest cardiovascular and renal benefits of ingesting small amounts of ethanol. Effects of ethanol, role of alcohol dehydrogenase (ADH) or of 20-hydroxyeicosatetraenoic acid (20-HETE) in podocytes of the glomerular filtration barrier have not been reported. We found that mouse podocytes at baseline generate 20-HETE and express ADH but not CYP2e1. Ethanol at high concentrations altered the actin cytoskeleton, induced CYP2e1, increased superoxide production and inhibited ADH gene expression. Ethanol at low concentrations upregulated the expression of ADH and CYP4a12a. 20-HETE, an arachidonic acid metabolite generated by CYP4a12a, blocked the ethanol-induced cytoskeletal derangement and superoxide generation. Ethanol at high …

Renal And Hematological Effects Of Clcf-1, A B-Cell-Stimulating Cytokine Of The Il-6 Family., Virginia J. Savin, Mukut Sharma, Jianping Zhou, David Gennochi, Timothy Fields, Ram Sharma, Ellen T. Mccarthy, Tarak Srivastava, Jos Domen, Aurélie Tormo, Jean-François Gauchat

Manuscripts, Articles, Book Chapters and Other Papers

CLCF-1 is a cytokine known for B-cell stimulation and for neurotrophic properties. We have identified CLCF-1 as a potential injurious factor in the human renal disease focal segmental glomerulosclerosis (FSGS). We investigated its effects on renal cells and renal function in in vitro and in vivo studies. Methods include measurement of the effect of CLCF-1 on phosphorylation of target molecules of the JAK/STAT pathway, on cytoskeleton and cell morphology in cultured podocytes, on albumin permeability of isolated rat glomeruli, and on tissue phosphorylation and urine albumin after acute or chronic CLCF-1 injection. In addition, cell sorting was performed to determine …

Allergen Immunotherapy For Allergic Asthma: Protocol For A Systematic Review., Sangeeta Dhami, Ulugbek Nurmatov, Ioana Agache, Susanne Lau, Antonella Muraro, Marek Jutel, Graham Roberts, Cezmi Akdis, Matteo Bonini, Moises Calderon, Thomas Casale, Ozlem Cavkaytar, Linda Cox, Pascal Demoly, Breda Flood, Eckard Hamelmann, Kenji Izuhara, Ömer Kalayci, Jörg Kleine-Tebbe, Antonio Nieto, Nikolaos Papadopoulos, Oliver Pfaar, Lanny Rosenwasser, Dermot Ryan, Carsten Schmidt-Weber, Stan Szefler, Ulrich Wahn, Roy-Gerth Van Wijk, Jamie Wilkinson, Aziz Sheikh

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for Allergic Asthma. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of allergic asthma.

METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised.

DISCUSSION: The findings from this review will be used …

Nonthermal Atmospheric Pressure Plasma Enhances Mouse Limb Bud Survival, Growth, And Elongation., Natalie Chernets, Jun Zhang, Marla J Steinbeck, Deepa S Kurpad, Eiki Koyama, Gary Friedman, Theresa A. Freeman

Department of Orthopaedic Surgery Faculty Papers

The enhanced differentiation of mesenchymal cells into chondrocytes or osteoblasts is of paramount importance in tissue engineering and regenerative therapies. A newly emerging body of evidence demonstrates that appendage regeneration is dependent on reactive oxygen species (ROS) production and signaling. Thus, we hypothesized that mesenchymal cell stimulation by nonthermal (NT)-plasma, which produces and induces ROS, would (1) promote skeletal cell differentiation and (2) limb autopod development. Stimulation with a single treatment of NT-plasma enhanced survival, growth, and elongation of mouse limb autopods in an in vitro organ culture system. Noticeable changes included enhanced development of digit length and definition of …

The Influence Of Positive And Negative Death Attitudes On Medical Students' Empathy And Attitudes Toward End-Of-Life Care, Elizabeth Palumbo

PCOM Psychology Dissertations

This quantitative study employed a cross-sectional survey research design in order to examine the relationships between medical students’ death attitudes, empathy, and attitudes toward end-of-life care. The participants were 206 medical students currently enrolled in the Doctor of Osteopathic Medicine program at the Philadelphia College of Osteopathic Medicine, Philadelphia campus. Results indicated that there were no significant differences in the level of empathy between medical students who held strong positive death attitudes and medical students with strong negative death attitudes. However, results indicated that significant differences existed in attitudes toward end-of-life care between medical students who held strong positive death …

Neurocognitive Patterns, Symptom Clusters, And Premorbid Factors That Predict Protracted Recovery From Concussion In Females, Sarah Pulaski

PCOM Psychology Dissertations

Concussion is an increasingly diagnosed injury that affects individuals of all ages. Although the underlying cause is unknown, research has demonstrated that females who sustain a concussion experience longer recoveries. Existing research has documented a relationship between age, gender, post-concussive headache and mental health conditions, and recovery; however, limited research has investigated the relationship between premorbid clinical variables and recovery. Research on post-injury neurocognitive declines and recovery has also demonstrated varied findings. Moreover, dizziness has been identified as significantly predictive of prolonged recovery, but no studies have investigated the effect of premorbid headache conditions on the development of dizziness. The …

Removal Of Partly Threaded Cannulated Screws After Treatment Of Slipped Capital Femoral Epiphysis: A Pilot Study, Nathan T. Morrell, Ian A. Power, Dukens Labaze, Elizabeth A. Szalay

UNM Orthopaedic Research Journal

Background: Partly threaded cannulated screws (PTCS) are currently recommended for management of slipped capital femoral epiphysis (SCFE), but no advantage of these screws over fully threaded cannulated screws (FTCS) has been demonstrated. We investigated whether PTCS are more difficult to remove than FTCS.

Methods: The records of 33 patients who underwent implant removal after operative treatment of SCFE were reviewed, and the following data were collected: age and sex of the patient, type of screw used (partly or fully threaded), length of removal operation, and any comments on the difficulty of screw removal.

Results: Sixty-one percent of operative reports for …

Manufacturing Doubt About Endocrine Disrupter Science - A Rebuttal Of Industry-Sponsored Critical Comments On The Unep/Who Report "State Of The Science Of Endocrine Disrupting Chemicals 2012", Åke Bergman, Georg Becher, Bruce Blumberg, Poul Bjerregaard, Riana Bornman, Ingvar Brandt, Stephanie Casey, Heloise Frouin, Linda Giudice, Jerrold J. Heindel, Taisen Iguchi, Susan Jobling, Karen A. Kidd, Andreas Kortenkamp, P. Monica Lind, Derek Muir, Roseline Ochieng, Erik Ropstad, Peter S. Ross, Niels Erik Skakkebaek, Jorma Toppari, Laura N. Vandenberg, Tracey J. Woodruff, R. Thomas Zoeller

Paediatrics and Child Health, East Africa

We present a detailed response to the critique of “State of the Science of Endocrine Disrupting Chemicals 2012” UNEP/WHO, 2013) by financial stakeholders, authored by Lamb et al. (2014). Lamb et al.'s claim that UNEP/WHO (2013) does not provide a balanced perspective on endocrine disruption is based on incomplete and misleading quoting of the report through omission of qualifying statements and inaccurate description of study objectives, results and conclusions. Lamb et al. define extremely narrow standards for synthesizing evidence which are then used to dismiss the UNEP/WHO 2013 report as flawed. We show that Lamb et al. misuse conceptual frameworks …

Adipocyte-Induced Inflammation In Prostate Tumor Progression In Bone: Role Of Cxcr2 And Osteopontin, Aimalie Lynnette Hardaway

Wayne State University Dissertations

Abstract

Prostate cancer (PCa) is the second leading cause of cancer-related deaths among men. Evidence suggests that age and obesity, conditions associated with adipocyte accumulation in the bone marrow, are linked to increased risk of developing PCa and progressing to metastatic disease. Studies presented in this dissertation were based on the hypothesis that metastatic progression in bone is a result of a cooperative effort between bone marrow adipocytes, macrophages, osteoclasts, and PCa cells. We specifically focused on two adipocyte-supplied chemokines, CXCL1 and CXCL2, and bone marrow macrophage-secreted osteopontin as key drivers of pro-inflammatory environment in the bone marrow and important …

Heterometallic Titanium–Gold Complexes Inhibit Renal Cancer Cells In Vitro And In Vivo, Jacob Fernandez-Gallardo, Benelita T. Elie, Tanmoy Sadhukha, Swayam Prabha, Mercedes Sanau, Susan A. Rotenberg, Joe W. Ramos, Maria Contel

Publications and Research

Following recent work on heterometallic titanocene–gold complexes as potential chemotherapeutics for renal cancer, we report here on the synthesis, characterization and stability studies of new titanocene complexes containing a methyl group and a carboxylate ligand (mba ¼ S–C6H4–COO) bound to gold(I)-phosphane fragments through a thiolate group [(h-C5H5)2TiMe(m-mba)Au(PR3)]. The compounds are more stable in physiological media than those previously reported and are highly cytotoxic against human cancer renal cell lines. We describe here preliminary mechanistic data involving studies on the interaction of selected compounds with plasmid (pBR322) DNA used as a model nucleic acid, and with selected protein kinases from a …

Gentamicin Differentially Alters Cellular Metabolism Of Cochlear Hair Cells As Revealed By Nad(P)H Fluorescence Lifetime Imaging, Lyandysha V. Zholudeva, Kristina G. Ward, Michael G. Nichols, Heather Jensen Smith

Journal Articles: Eppley Institute

Aminoglycoside antibiotics are implicated as culprits of hearing loss in more than 120,000 individuals annually. Research has shown that the sensory cells, but not supporting cells, of the cochlea are readily damaged and/or lost after use of such antibiotics. High-frequency outer hair cells (OHCs) show a greater sensitivity to antibiotics than high- and low-frequency inner hair cells (IHCs). We hypothesize that variations in mitochondrial metabolism account for differences in susceptibility. Fluorescence lifetime microscopy was used to quantify changes in NAD(P)H in sensory and supporting cells from explanted murine cochleae exposed to mitochondrial uncouplers, inhibitors, and an ototoxic antibiotic, gentamicin (GM). …

Characterization Of Cd8+ T Cell Differentiation Following Sivδnef Vaccination By Transcription Factor Expression Profiling, James M. Billingsley, Premeela A. Rajakumar, Michelle A. Connole, Nadine C. Salisch, Sama Adnan, Yury V. Kuzmichev, Henoch S. Hong, R. Keith Reeves, Hyung-Joo Kang, Wenjun Li, Qingsheng Li, Ashley T. Haase, R. Paul Johnson

Nebraska Center for Virology: Faculty Publications

The onset of protective immunity against pathogenic SIV challenge in SIVΔnef-vaccinated macaques is delayed for 15-20 weeks, a process that is related to qualitative changes in CD8⁺ T cell responses induced by SIVΔnef. As a novel approach to characterize cell differentiation following vaccination, we used multi-target qPCR to measure transcription factor expression in naïve and memory subsets of CD8+⁺ T cells, and in SIV-specific CD8⁺ T cells obtained from SIVΔnef-vaccinated or wild type SIVmac239-infected macaques. Unsupervised clustering of expression profiles organized naïve and memory CD8⁺ T cells into groups concordant with cell surface phenotype. Transcription factor …

Escherichia Coli Surface Display Of Single-Chain Antibody Vrc01 Against Hiv-1 Infection, Lin-Xu Wang, Michael Mellon, Dane Bowder, Meghan Quinn, Danielle Shea, Charles Wood, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus type 1 (HIV-1) transmission and infection occur mainly via the mucosal surfaces. The commensal bacteria residing in these surfaces can potentially be employed as a vehicle for delivering inhibitors to prevent HIV-1 infection. In this study, we have employed a bacteria-based strategy to display a broadly neutralizing antibody VRC01, which could potentially be used to prevent HIV-1 infection. The VRC01 antibody mimics CD4-binding to gp120 and has broadly neutralization activities against HIV-1. We have designed a construct that can express the fusion peptide of the scFv-VRC01 antibody together with the autotransporter β-barrel domain of IgAP gene from …

The Hippo/Yap Pathway Interacts With Egfr Signaling And Hpv Oncoproteins To Regulate Cervical Cancer Progression, Chunbo He, Dagan Mao, Guohua Hua, Xiangmin Lv, Xingcheng Chen, Peter C. Angeletti, Jixin Dong, Steven W. Remmenga, Kerry J. Rodabaugh, Jin Zhou, Paul F. Lambert, Peixin Yang, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

The Hippo signaling pathway controls organ size and tumorigenesis

through a kinase cascade that inactivates Yes-associated

protein (YAP). Here, we show that YAP plays a central role in

controlling the progression of cervical cancer. Our results suggest

that YAP expression is associated with a poor prognosis for cervical

cancer. TGF-α and amphiregulin (AREG), via EGFR, inhibit the Hippo

signaling pathway and activate YAP to induce cervical cancer cell

proliferation and migration. Activated YAP allows for up-regulation

of TGF-α, AREG, and EGFR, forming a positive signaling loop to

drive cervical cancer cell proliferation. HPV E6 protein, a major

etiological molecule of …