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Articles 1 - 30 of 72
Full-Text Articles in Medicine and Health Sciences
Comparisons Between The Nod And Nor Mouse: Insight Into Diabetes Pathogenesis And Protection, Joseph Guy Daft
Comparisons Between The Nod And Nor Mouse: Insight Into Diabetes Pathogenesis And Protection, Joseph Guy Daft
All ETDs from UAB
Type 1 Diabetes (T1D) is defined as the selective immune destruction of insulin producing beta cells within the islet. A new emphasis has been put on the role of the gastrointestinal (GI) tract in T1D; however, there is much more to learn about this relationship. Distinct differences have been observed in the intestinal permeability, barrier function, commensal microbiota, and mucosal innate and adaptive immunity of patients and animals with T1D, when compared to healthy controls. The non-obese diabetic (NOD) mouse and the BioBreeding diabetes prone (BBdp) rat are commonly used to models to study T1D in humans. Most murine studies …
Osteomimmunology Of Bone Fracture Healing And Cell And Gene Therapy Approaches For Nonunion Bone Defects, Seth G. Levy
Osteomimmunology Of Bone Fracture Healing And Cell And Gene Therapy Approaches For Nonunion Bone Defects, Seth G. Levy
All ETDs from UAB
Despite the body's ability to repair bone fractures under normal circumstances, up to 10% of the 7.9 million fractures suffered in the United States each year do not achieve bony union. Bone fractures heal with overlapping phases of inflammation, cell proliferation, and bone remodeling. Osteogenesis and angiogenesis are known to work in concert to control many stages of this process, but when one is impaired it leads to failure of bone healing, referred to as a nonunion. Such nonunion fractures often result from critical-size defects that will not completely heal over the natural lifetime of the animal. Based on this …
Calreticulin Regulates Tgf-Ss Stimulated Extracellular Matrix Production, Kurt Zimmerman
Calreticulin Regulates Tgf-Ss Stimulated Extracellular Matrix Production, Kurt Zimmerman
All ETDs from UAB
Calreticulin (CRT) is an ER chaperone and regulator of Ca2+ signaling which is increased following ER stress and in fibrotic and vascular fibroproliferative disorders. Previously, we demonstrated that ER CRT regulates type I collagen transcript, trafficking, secretion, and processing into the extracellular matrix (ECM). These studies investigated the role of CRT in regulating ECM production through control TGF-ß dependent signaling pathways. Our studies show that CRT -/- mouse embryonic fibroblasts (MEFs), rat lung fibroblasts, and human IPF lung fibroblasts with siRNA knockdown of CRT had impaired production of type I collagen and fibronectin when stimulated with TGF-ß. Similarly, knockdown of …
Actions Of Grape Seed Extract In Rodent Brain And Differences In Metabolism Of Its Polyphenols In A Rodent Model Of Menopause, John Kenneth Cutts
Actions Of Grape Seed Extract In Rodent Brain And Differences In Metabolism Of Its Polyphenols In A Rodent Model Of Menopause, John Kenneth Cutts
All ETDs from UAB
Grape seed extract (GSE), a dietary supplement, has potential in the treatment and prevention of human chronic age-related diseases including cancers, cardiovascular diseases, and neurodegenerative diseases. GSE and adult hippocampal neurogenesis, independently, have enhanced learning and memory in rodents. We hypothesized that GSE enhances learning and memory, at least partially, by enhancing hippocampal neurogenesis. However, adult mice given GSE did not exhibit increased number of progenitor cells or new neurons, established markers of neurogenesis, in the dentate gyrus (DG). Also, 26-day-old pups whose mother was given GSE only while nursing had fewer new neurons in the DG compared to control …
Development Of A Patient-Derived Xenograft Model Of Ovarian Cancer To Characterize The Chemotherapy Resistant Population, Zachary Christopher Dobbin
Development Of A Patient-Derived Xenograft Model Of Ovarian Cancer To Characterize The Chemotherapy Resistant Population, Zachary Christopher Dobbin
All ETDs from UAB
Ovarian cancer while the second most common gynecologic malignancy is the most commons cause of death due to a gynecologic malignancy and the fifth most common cause of death to cancer in women. In 2014, there will be an expected 21,980 cases and 14,270 deaths. Unfortunately, the five-year survival for ovarian cancer is only 40% and this has barely increased over the past 30 years. New approaches need to be developed in order to study ovarian cancer and identify methods of overcoming chemotherapy resistance. This dissertation presents the work conducted in the development of a patient-derived xenograft model of ovarian …
Type I Interferons-Induced Follicular Translocation Of Lymphotoxin-Expressing Marginal Zone B Cells Initiates Lupus, Hao Li
All ETDs from UAB
Systemic lupus erythematosus (SLE) is characterized by elevation of type I interferon (IFN) signature genes and production of autoantibodies against apoptotic self-antigens. The complex nature of SLE, however, suggests that multiple immune dysregulations must integrate to initiate the disease. Here, we provided evidence that lupus can be initiated via type I IFNs-induced follicular translocation of membrane lymphotoxin (mLT)-expressing marginal zone (MZ) B cells in the spleen of lupus prone BXD2 mice. The mislocation of mLT+ MZ B cells induces two important pathogenic effects including deteriorations of marginal zone macrophages (MZMs) in the MZ, leading to defective clearance of apoptotic debris, …
Expression Of The Influenza Protein M2 During Viral Infection Inhibits Cftr Activity, James David Londino
Expression Of The Influenza Protein M2 During Viral Infection Inhibits Cftr Activity, James David Londino
All ETDs from UAB
The purpose of these dissertation studies was to 1) determine whether influenza infection alters CFTR activity in polarized epithelium; 2) measure CFTR expression and activity in cells co-expressing influenza M2 protein; and 3) examine the role of M2 on the alteration of CFTR during viral infection. We determined that infection of polarized primary epithelial cells with influenza decreases CFTR expression and activity. In addition, individual cells infected with influenza had decreased CFTR conductance as measured by whole-cell patch clamp. We also found that the influenza ion channel, matrix protein 2 (M2), alone reduced CFTR expression and activity. M2 is expressed …
Contribution Of Kv4.2 To Neuronal Hyperexcitability In A Mouse Model Of Alzheimer's Disease, Alicia Marie Hall
Contribution Of Kv4.2 To Neuronal Hyperexcitability In A Mouse Model Of Alzheimer's Disease, Alicia Marie Hall
All ETDs from UAB
The incidence of Alzheimer's disease (AD) is increasing with the aging population and an astonishing 5.2 million Americans are affected by AD, the most common cause of dementia. Cognitive impairment worsens with declining hippocampal function. Neuronal hyperexcitability occurs early in the pathogenesis of AD and contributes to network imbalance and the seizure activity seen in AD patients. In other disorders with neuronal hyperexcitability, dysfunction in the dendrites often contributes, but dendritic excitability has not been studied in AD models. We used patch-clamp recordings to directly examine dendritic excitability in the CA1 region of the hippocampus. We found that dendrites, but …
Cd5 Regulation Of T Helper Cell Differentiation And Cytokine Signaling, Donald Mcguire
Cd5 Regulation Of T Helper Cell Differentiation And Cytokine Signaling, Donald Mcguire
All ETDs from UAB
CD5 is expressed on T and B1a cells and is an important regulator of cell survival and activation. Engagement of CD5 promotes cell survival through the activation of the serine threonine kinase CK2. Mice with genetic abrogation of CD5 binding to CK2 (CD5∆CK2bd) exhibited reduced severity of experimental autoimmune encephalomyelitis that was associated with increased activation induced cell death. In addition to inhibiting cell death, CD5 activation of CK2 significantly enhances Th17 differentiation. Loss of CD5-CK2 signaling reduces the generation of Th17 cells despite an unexpected increase in pSTAT3 levels. The mechanisms of CD5's enhancement of Th17 differentiation have not …
Glial Fibrillary Acidic Protein And Gliosis: Is Gfap More Than A Marker?, Heather Renee Minkel
Glial Fibrillary Acidic Protein And Gliosis: Is Gfap More Than A Marker?, Heather Renee Minkel
All ETDs from UAB
Alexander Disease (AxD) is a `gliopathy' caused by toxic, dominant gain-of-function mutations in the gene encoding glial fibrillary acidic protein (GFAP). Two distinct types of AxD exist. Type I AxD affected individuals develop cerebral symptoms by four years of age and generally suffer from macrocephaly, seizures, and physical and mental delays. As detection and diagnosis have improved, a larger portion, now about half of all AxD patients diagnosed, have onset >4 years and brainstem/spinal cord involvement. These type II AxD patients typically experience ataxia, palatal myoclonus, dysphagia and dysphonia. To date no study has examined a mechanistic link between the …
The Role Of Primary Cilia In Mammary Gland And Skeletal Development, Elizabeth Mitchell
The Role Of Primary Cilia In Mammary Gland And Skeletal Development, Elizabeth Mitchell
All ETDs from UAB
Primary cilia (PC) extend from the cell body into the microenvironment detecting chemical and mechanical signals, and are required for proper development. To evaluate loss of primary cilia in mammary gland development, we developed mouse models with deletion of PC in mammary epithelial compartments. No discernable alterations to mammary development were observed in MMTV-Cre- or K14-Cre; Ift88Del lines. PC were expressed at high levels on cells in mammosphere culture; however, PC were not required for mammosphere renewal. The inability to find a significant mammary developmental phenotype in our mouse models suggested primary cilia don't have a significant function in differentiated …
The Role Of The Planar Cell Polarity Pathway In The Second Heart Field During Outflow Tract Morphogenesis, Tanvi Sinha
The Role Of The Planar Cell Polarity Pathway In The Second Heart Field During Outflow Tract Morphogenesis, Tanvi Sinha
All ETDs from UAB
Outflow Tract (OFT) malformations underlie a majority of congenital heart defects (CHD) in humans and are a leading cause of childhood mortality. The OFT, which gives rise to the aorta and pulmonary artery of the heart, relies on the contribution of the Second Heart Field (SHF) progenitors in the pharyngeal and the splanchnic mesoderm, outside of the initial heart. OFT morphogenesis requires highly regulated SHF development involving the proliferation, differentiation and deployment of the SHF progenitors to the heart. Extensive studies elegantly demonstrate how transcriptional networks integrating signaling input from multiple pathways finely balance the proliferation and differentiation of SHF …
Translocation Of Shed Syndecan-1 To The Nucleus: A Novel Mechanism Of Tumor-Host Crosstalk, Mark Stewart
Translocation Of Shed Syndecan-1 To The Nucleus: A Novel Mechanism Of Tumor-Host Crosstalk, Mark Stewart
All ETDs from UAB
Multiple myeloma is a hematological malignancy of plasma cells that disseminates throughout the body. Crosstalk between myeloma and host cells is critical to the establishment of a microenvironment conducive to tumor growth and progression. An important mediator of this crosstalk is syndecan-1, a heparan sulfate proteoglycan. Syndecan-1 is proteolytically shed from the surface of myeloma cells and is abundant in the bone marrow microenvironment and serum of myeloma patients. Shed syndecan-1 facilitates tumor-host crosstalk within the microenvironment to drive tumor growth, angiogenesis, and metastasis. We now report for the first time that shed syndecan-1 can be taken up by a …
Assessing The Active Kinome Of Influenza Virus Infected A549 Cells, Colm Atkins
Assessing The Active Kinome Of Influenza Virus Infected A549 Cells, Colm Atkins
All ETDs from UAB
Influenza A Virus is a respiratory pathogen of the family Orthomyxoviridae and causes significant worldwide morbidity and mortality during seasonal epidemics and periodic pandemics. As with all viruses, influenza's limited coding capacity requires the use of host proteins and processes in its replication and release cycle. Phosphorylation, mediated by cellular kinases and phosphatases, represents a significant mechanism of post-translational modification of cellular products, and is responsible for regulating the activi-ty, lifespan and localization of many lipids and proteins in host-cells. Several cellular kinases have been associated with various steps of the Influenza lifecycle, including PKC-ßII (viral entry), PKR (host defense), …
Il-8 Is Necessary And Sufficient For X-Ray Radiation Enhanced Endothelial Adhesion., Stephen Kyle Babitz
Il-8 Is Necessary And Sufficient For X-Ray Radiation Enhanced Endothelial Adhesion., Stephen Kyle Babitz
All ETDs from UAB
Ionizing radiation (IR) is a potent inflammatory stimulus to the human body. In the vasculature, inflammation is a major contributing factor for atherosclerosis. In addition, radiation from several sources has been linked with increased risk for multiple cardiovascular complications. A key compnent of radiation associated inflammation is an increase in the adhesiveness of the endothelium which leads to a pathogenic accumulation of leukocytes in the vascular wall. This is one of the initial steps in vascular inflammation and leads to a number of adverse complications such as heart disease and stroke. The molecular mechanisms behind radiaton enhanced endothelial adhesion have …
Cd5-Dependent Ck2 Activation Is Critical For The Maintenance Of B-1a B Cells, Kevin S. Cashman
Cd5-Dependent Ck2 Activation Is Critical For The Maintenance Of B-1a B Cells, Kevin S. Cashman
All ETDs from UAB
CD5 has classically been shown to act as a negative regulator of antigen receptor signaling, however recent evidence has discerned that the CD5 molecule contains a previously undefined cytoplasmic domain which constitutively binds inactive CK2 and facilitates its activation through CD5 ligation. With the development of a mouse model which contains a micro-deletion knock-in form of CD5 which lacks the amino acids necessary to facilitate this CD5-CK2 interaction, it is now understood that CD5 plays a more significant role in cellular physiology than previously appreciated. T cells from this mouse model show increased AICD and dysregulation in T helper subset …
Role Of Immunoregulatory Cytokines Il-12 And Il-23 In Skin Cancer, Tahseen H. Nasti
Role Of Immunoregulatory Cytokines Il-12 And Il-23 In Skin Cancer, Tahseen H. Nasti
All ETDs from UAB
The incidence of new cases of skin cancer, which includes non-melanoma epithelial tumors and melanoma, has increased dramatically over the last few decades. Approximately 75% of all skin cancer-related deaths is due to melanoma, which is one of the most aggressive and difficult cancers to treat. The initiating events and mechanisms that influence melanoma development are not fully known, due in part to a paucity of animal models amenable to identifying new oncogenic mutations, and investigating mechanisms of immunosurveillance. Transgenic mouse models often harbor an activating mutation in a known oncogene in all somatic cells, and its widespread expression from …
Targeted Delivery Of Osteoinductive Peptides To Bone Graft Utilizing A Calcium Binding Domain To Enhance The Regenerative Potential, Jennifer Leigh Bain
Targeted Delivery Of Osteoinductive Peptides To Bone Graft Utilizing A Calcium Binding Domain To Enhance The Regenerative Potential, Jennifer Leigh Bain
All ETDs from UAB
Bone grafting procedures are common practice. Autogenous bone is considered optimal, however, complications associated with bone harvesting often lead clinicians to use off-the-shelf materials that have limited osteoinductivity. Alternatively, bioactive factors passively adsorbed onto various carriers are available. These materials, while effective, are expensive to produce, require supraphysiological doses, and have adverse side effects due to dissemination from the graft site. This dissertation aims to reintroduce osteoinductive factors to bone grafts to enhance regenerative capacity. Specifically, we utilized negatively-charged calcium-binding domains (polyglutamate) to anchor two osteoinductive peptides bone graft materials including an allograft, xenograft, alloplast, and bone cement. The peptides …
Recognition Of Hiv-1 Cryptic Epitopes During Infection And Following Vaccination, Anne Bet
Recognition Of Hiv-1 Cryptic Epitopes During Infection And Following Vaccination, Anne Bet
All ETDs from UAB
Cryptic epitopes (CE) are a unique set of human leukocyte antigen class I (HLA-I)-restricted peptides that are encoded by alternative reading frames (ARFs) of genes. During human immunodeficiency virus-1 (HIV-1) infection, CE translated from either sense or antisense transcripts elicit epitope-specific CD8 T cell responses. Previous studies using simian immunodeficiency virus (SIV)-vaccinated animals have shown that an increased breadth of CD8 T cell responses is correlated with controlling viral replication, therefore stressing the potential clinical benefit of vaccine-induced T cell responses to a diverse set of viral epitopes. Yet, the genetic profiles and immunological significance of CE remain poorly understood. …
The Modulation Of High Density Lipoprotein Metabolism In Systemic Lupus Erythematosus, Leland Latham Black
The Modulation Of High Density Lipoprotein Metabolism In Systemic Lupus Erythematosus, Leland Latham Black
All ETDs from UAB
Apolipoprotein A-I (ApoA-I), the major lipid-binding protein of high-density lipoprotein (HDL), can suppress inflammation and autoimmunity in hypercholesterolemic mice by modulating cellular cholesterol homeostasis and lipid oxidation. However, the cellular and molecular mechanisms involved are poorly understood, and whether ApoA-I or ApoA-I mimetic peptides can similarly exert immunosuppressive effects or improve inflammatory organ disease in SLE under normolipidemic conditions remains unresolved. We therefore first took a genetic approach in which bone marrow from SLE-prone Sle123 mice was transferred into wild-type, ApoA-I knockout (ApoA-I-/-) and ApoA-I transgenic (ApoA-Itg) mice. Transgenic expression of ApoA-I suppressed CD4+ T and B lymphocyte activation, reduced …
The Role Of The Developing Microbiome In Mucosal Defense Of The Neonatal Gut, Emily G. Blosser
The Role Of The Developing Microbiome In Mucosal Defense Of The Neonatal Gut, Emily G. Blosser
All ETDs from UAB
Neonatal late-onset sepsis is invasive infection occurring after the first 48 hours of life, and one of the leading causes of death among preterm infants in the United States and abroad. Infections with Gram-negative bacteria, such as Klebsiella pneumonia, occurring when bacteria translocate across premature gut epithelium into the bloodstream, can be particularly severe. Preterm infants in the neonatal intensive care unit undergo intense antibiotic regimens due to high risk of infection. Paradoxically, prolonged exposure of preterm infants to empiric antibiotic therapy early in the hospital stay is associated with increased risk of intestinal infection and death after adjustment for …
The Involvement Of The Ca2+-Independent Phospholipase A2ss In The Pathogenesis Of Type 1 Diabetes, Robert N. Bone
The Involvement Of The Ca2+-Independent Phospholipase A2ss In The Pathogenesis Of Type 1 Diabetes, Robert N. Bone
All ETDs from UAB
Type 1 diabetes is a metabolic disease characterized by hyperglycemia, an absolute deficiency in insulin, and the autoimmune-mediated destruction of pancreatic islet ß-cells. Since exogenous insulin does not effectively duplicate native ß-cell function and the need persists for life, strategies to prevent ß-cell death or promote ß-cell survival are expected to provide beneficial outcomes. Based on reports that Akt1 promotes ß-cell survival and proliferation, administration of viral vectors modified to effectively deliver constitutively active (CA)-Akt1 to ß-cells would be expected to be beneficial for the ß-cell. In freshly isolated islets, CA-Akt1 promoted ex vivo islet cell survival and ß-cell survival. …
Engineering Fibroblast-Remodeled Electrospun Matrices For Full-Thickness Skin Regeneration, Paul Bonvallet
Engineering Fibroblast-Remodeled Electrospun Matrices For Full-Thickness Skin Regeneration, Paul Bonvallet
All ETDs from UAB
Skin is often severely damaged, resulting in the need for surgical intervention. There are many limitations to current therapies, therefore a synthetic skin graft would be invaluable for skin regeneration. The focus of the current study is on developing engineered scaffolds with embedded dermal fibroblasts that can be remodeled into native skin tissue upon implantation. To achieve this goal we created electrospun scaffolds composed of collagen I and polycaprolactone (PCL), and then introduced pores to allow fibroblast infiltration. In initial experiments performed to optimize pore size and collagen to PCL concentration, we determined that a 160 µm pore diameter, and …
The Multifaceted Role Of Neutrophils In Hiv-1-Infection, Nathan Bowers
The Multifaceted Role Of Neutrophils In Hiv-1-Infection, Nathan Bowers
All ETDs from UAB
In recent years, a new appreciation of the role of neutrophils in regulating the immune system has emerged. Neutrophils are the most abundant leukocyte population and are traditionally recognized as essential effector cells of the innate immune system in the host defense against invading organisms. Neutrophils play a critical role in controlling bacterial and fungal infections by multiple mechanisms including phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs). Neutrophils have been shown to play important roles in viral pathogenesis, a knowledge gap exists in our understanding of the function of neutrophils in individuals infected with human immunodeficiency virus-1 (HIV-1). …
Synaptic And Circuit Mechanisms Of Glutamate Spillover Signaling, Luke Teichert Coddington
Synaptic And Circuit Mechanisms Of Glutamate Spillover Signaling, Luke Teichert Coddington
All ETDs from UAB
Glutamate is the most prominent fast excitatory neurotransmitter released at mammalian central synapses, where point-to-point activation of receptors in postsynaptic densities is accepted to be the primary pathway for information flow through neural circuits. More controversial are the activities of synaptically-released glutamate outside the synaptic cleft of origin, as "spillover" glutamate may signal through neighboring synapses or through extrasynaptic receptors. The role of such extrasynaptic signaling in physiological neuronal communication is unproven and its inappropriate occurrence has been proposed to underlie a range of neurodegenerative conditions. Elucidation of spillover signaling mechanisms thus benefits our understanding of the brain in both …
Alpha-Camkii-Induced Vegf Expression Is Critical For The Growth Of Human Osteosarcoma, Paul Glenn Daft
Alpha-Camkii-Induced Vegf Expression Is Critical For The Growth Of Human Osteosarcoma, Paul Glenn Daft
All ETDs from UAB
Osteosarcoma (OS) is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. Despite improvements in OS treatment, more specific molecular targets are needed. One target of interest is alpha-Ca2+/calmodulin-dependent protein kinase II (α-CaMKII), a ubiquitous mediator of Ca2+-linked signaling, which has been shown to regulate tumor cell proliferation. Here, we show that α-CaMKII is highly expressed in primary OS tissue, and α-CaMKII deletion in human OS cell lines significantly reduces tumor burden in vivo. This inhibition of α-CaMKII results in decreased vascular endothelial growth factor (VEGF) protein secretion. Highly aggressive OS cells express VEGF receptor …
Examining The Role Of G Protein-Coupled Estrogen Receptor 1 (Gper) Activation In 17beta-Estradiol-Mediated Protection In Traumatic Brain Injury, Nicole Day
All ETDs from UAB
Traumatic brain injury (TBI) affects millions of persons per year, potentially leading to permanent disability or death, and exacts a staggering financial toll. Despite the severity of this public health problem, there are no clinically proven pharmacotherapeutics available that effectively attenuate the secondary neurochemically-mediated damage that follows the initial biomechanical insult. In addition, the heterogeneous nature of TBI and complexity of secondary injury cascades suggest that a polytherapeutic approach could be a powerful strategy with which to simultaneously target more than one deleterious pathway. Recently, sex steroid hormones have sparked interest as possible neuroprotective agents after traumatic injury. One of …
Evidence Of Altered Ampa Receptor Localization And Regulation In Schizophrenia, Jana Drummond
Evidence Of Altered Ampa Receptor Localization And Regulation In Schizophrenia, Jana Drummond
All ETDs from UAB
Although the glutamate hypothesis of schizophrenia posits altered glutamatergic transmission is occurring in this illness, the precise mechanisms be-hind these proposed changes in schizophrenia brain remain elusive. Recent evidence from our laboratory supports a model of altered forward trafficking of glutamate receptors to synaptic membranes in schizophrenia, which could contribute to changes in neurotransmission. The AMPA subtype of ionotropic glutamate receptor (AMPAR), is the main facilitator of fast, excitatory neurotransmission in the brain, and changes in AMPAR number at synapses may control synaptic strength and plasticity. One mechanism that could alter AMPAR trafficking to synapses is abnormal expression of AMPAR …
Mitochondrial Genetics Modify Body Composition, Metabolic Efficiency And Myocardial Metabolism, Kimberly Joanne Dunham
Mitochondrial Genetics Modify Body Composition, Metabolic Efficiency And Myocardial Metabolism, Kimberly Joanne Dunham
All ETDs from UAB
Obesity and cardiometabolic pathologies have reached epidemic levels worldwide over the last 30 years. Currently, the majority of research investigating possible genetic causes of obesity is focused on nuclear DNA (nDNA). While this has lead to the development of numerous animal models, it is apparent the etiology of obesity is more complex than single gene mutations. Recently it has also been suggested that mitochondrial DNA (mtDNA) mutations sustained during evolution as a consequence of our prehistoric environment may influence individual propensity and risk of disease. Contemporary human populations are no longer faced with the challenges of our ancestors such as …
The Role Of Wnt5a In Tumor Suppression And Differentiation, Stephanie Easter
The Role Of Wnt5a In Tumor Suppression And Differentiation, Stephanie Easter
All ETDs from UAB
TGF-beta and the Wnt signaling pathways play key roles in regulating ductal growth and branching morphogenesis in the mammary gland. Disruption to this signaling can cause deregulation of the normal mammary stem cell population and foster an environment favorable for tumorigenesis and recurrence. Recent studies show that TGF-beta up-regulates expression of the non-canonical Wnt, Wnt5a, in the mammary gland and that Wnt5a antagonizes canonical Wnt/beta-catenin signaling in mammary epithelial cells. Canonical Wnt/beta-catenin signaling has been strongly implicated in expanding the mammary stem/progenitor cell pool. Here, we test the hypothesis that Wnt5a suppresses the expansion of the mammary stem and progenitor …