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Herbal Marijuana Alternatives Investigation: K2 And Spice: A Masters Thesis, Christopher D. Rosenbaum Dec 2011

Herbal Marijuana Alternatives Investigation: K2 And Spice: A Masters Thesis, Christopher D. Rosenbaum

GSBS Dissertations and Theses

Background

Herbal marijuana alternatives (HMA), legal plant products adulterated with synthetic cannabinoid receptor agonists, represent a growing public health concern. Only a few case reports describe HMA and synthetic cannabinoid’s clinical toxicity. We describe an outbreak of HMA abuse primarily in the Midwest, the clinical presentation of HMA toxicity, and clinical and forensic testing.

Methods

During the course of ongoing surveillance for emerging drugs of abuse between November 2009 and August 2010, we retrospectively and prospectively identified a convenience sample comprising 81 cases of abuse of HMA products. Subject demographics, vital signs, lab results and urine were obtained (when ...


Intestine Homeostasis And The Role Of Tumor Suppressor Gene 101 In Drosophila Melanogaster: A Dissertation, Madhurima Chatterjee Dec 2011

Intestine Homeostasis And The Role Of Tumor Suppressor Gene 101 In Drosophila Melanogaster: A Dissertation, Madhurima Chatterjee

GSBS Dissertations and Theses

Tissue homeostasis in the adult Drosophila melanogaster intestine is maintained by controlling the proper balance of stem cell self-renewal and differentiation. In the adult fly midgut, intestinal stem cells (ISCs) are the only dividing cells and their identity maintenance is crucial to the proper functioning of the fly gut. Various pathways such as Notch, JAK-STAT and Wingless are known to regulate ISC division and differentiation.

Here I used a pathogen feeding model to study conditions that accelerate ISC division and guide intestinal cell differentiation favoring enterocyte development. I also examined the role of Tumor Suppressor Gene 101 (TSG101) in ISC ...


Comparative Effectiveness Of Alendronate And Risedronate On The Risk Of Non-Vertebral Fractures In Older Women: An Instrumental Variables Approach: A Dissertation, Yong Chen Dec 2011

Comparative Effectiveness Of Alendronate And Risedronate On The Risk Of Non-Vertebral Fractures In Older Women: An Instrumental Variables Approach: A Dissertation, Yong Chen

GSBS Dissertations and Theses

Osteoporosis is a significant public health problem in the U.S. It not only affects the physical well-being of the older women but also creates a substantial financial burden for the health care system. The mainstay of osteoporosis medications is bisphosphonate treatment of which alendronate and risedronate are the most commonly prescribed in clinical practice. However, there have been no head-to-head randomized controlled trials (RCTs) evaluating the effects of these two bisphosphonates on fracture outcomes.

In the absence of RCTs, observational studies are necessary to provide alternative evidence on the comparative effectiveness between alendronate and risedronate on fracture outcomes. However ...


Cannabis Use And Bipolar Disorder: Bipolar Disorder Case Identification And Cannabis Use Risk Assessment: A Dissertation, Patrick J. Mccabe Dec 2011

Cannabis Use And Bipolar Disorder: Bipolar Disorder Case Identification And Cannabis Use Risk Assessment: A Dissertation, Patrick J. Mccabe

GSBS Dissertations and Theses

Bipolar disorders (BD) are characterized by symptoms of grandiosity, decreased need for sleep, pressure to keep talking, flight of ideas, distractibility, increased goal-directed activities, psychomotor agitation, and excessive involvement in pleasurable activities. Those with a bipolar disorder have a high degree of psychiatric comorbidity including substance use disorders, and they also experience increased mortality. Despite the widespread recognition of BD as an important psychiatric condition, available population-based estimates for BD prevalence differs across data sources.

Cannabis is one of the most widely-used illicit substances. Evidence supports it as a risk factor for psychotic symptoms and disorders. Because populations with psychotic ...


Support Of Mitochondrial Dna Replication By Human Rad51: A Dissertation, Jay M. Sage Dec 2011

Support Of Mitochondrial Dna Replication By Human Rad51: A Dissertation, Jay M. Sage

GSBS Dissertations and Theses

The function of homologous DNA recombination in human mitochondria has been a topic of ongoing debate for many years, with implications for fields ranging from DNA repair and mitochondrial disease to population genetics. While genetic and biochemical evidence supports the presence of a mitochondrial recombination activity, the purpose for this activity and the proteins involved have remained elusive. The work presented in this thesis was designed to evaluate the mitochondrial localization of the major recombinase protein in human cells, Rad51, as well as determine what function it plays in the maintenance of mitochondrial DNA (mtDNA) copy number that is critical ...


Cellular And Molecular Mechanisms Driving Glial Engulfment Of Degenerating Axons: A Dissertation, Johnna E. Doherty Nov 2011

Cellular And Molecular Mechanisms Driving Glial Engulfment Of Degenerating Axons: A Dissertation, Johnna E. Doherty

GSBS Dissertations and Theses

The nervous system is made up of two major cell types, neurons and glia. The major distinguishing feature between neuronal cells and glial cells is that neurons are capable of transmitting action potentials while glial cells are electrically incompetent. For over a century glial cells were neglected and it was thought they existed merely to provide trophic and structural support to neurons. However, in the past few decades it has become increasingly clear that glial cell functions underlie almost all aspects of nervous system development, maintenance, and health. During development, glia act as permissive substrates for axons, provide guidance cues ...


Insights Into Er Translocation Channel Gating. Structural Regulation Of The Transition Between The Closed And Open Channel Conformations: A Dissertation, Steven F. Trueman Oct 2011

Insights Into Er Translocation Channel Gating. Structural Regulation Of The Transition Between The Closed And Open Channel Conformations: A Dissertation, Steven F. Trueman

GSBS Dissertations and Theses

The transition between the closed and open conformations of the Sec61 complex permits nascent protein insertion into the translocation channel. A critical event in this structural transition is the opening of the lateral translocon gate that is formed by four transmembrane (TM) spans (TM2, TM3, TM7 and TM8 in Sec61p) to expose the signal sequence-binding (SSB) site. To gain mechanistic insight into lateral gate opening, mutations were introduced into a lumenal loop (L7) that connects TM7 and TM8. The sec61 L7 mutants were found to have defects in both the posttranslational and cotranslational translocation pathways due to a kinetic delay ...


Autoregulatory And Paracrine Control Of Synaptic And Behavioral Plasticity By Dual Modes Of Octopaminergic Signaling: A Dissertation, Alex C. Koon Oct 2011

Autoregulatory And Paracrine Control Of Synaptic And Behavioral Plasticity By Dual Modes Of Octopaminergic Signaling: A Dissertation, Alex C. Koon

GSBS Dissertations and Theses

Synaptic plasticity—the ability of a synapse to change—is fundamental to basic brain function and behavioral adaptation. Studying the mechanisms of synaptic plasticity benefits our understanding of the formation of neuronal connections and circuitry, which has great implications in the field of learning and memory and the studies of numerous human diseases.

The Drosophila larval neuromuscular junction (NMJ) system is a powerful system for studying synaptic plasticity. The NMJ consists of at least two different types of motorneurons innervating the body wall muscles. Type I motorneurons controls muscle contraction using glutamate as the neurotransmitter, while type II are modulatory ...


Telomere Length Dynamics In Human T Cells: A Dissertation, Joel M. O'Bryan Oct 2011

Telomere Length Dynamics In Human T Cells: A Dissertation, Joel M. O'Bryan

GSBS Dissertations and Theses

Telomere length has been shown to be a critical determinant of T cell replicative capacity and in vivo persistence in humans. We evaluated telomere lengths in virus-specific T cells to understand how they may both shape and be changed by the maintenance of memory T cells during a subsequent virus re-infection or reactivation. We used longitudinal peripheral blood samples from healthy donors and samples from a long-term HCV clinical interferon therapy trial to test our hypotheses.

To assess T cell telomere lengths, I developed novel modifications to the flow cytometry fluorescence in situ hybridization (flowFISH) assay. These flowFISH modifications were ...


Using Light To Observe And Control Cellular Function: Improving Bioluminescence Imaging And Photocontrol Of Rho Gtpase Activation States: A Dissertation, Katryn R. Harwood Sep 2011

Using Light To Observe And Control Cellular Function: Improving Bioluminescence Imaging And Photocontrol Of Rho Gtpase Activation States: A Dissertation, Katryn R. Harwood

GSBS Dissertations and Theses

The dynamic processes that occur at specific times and locations in cells and/or whole organisms during cellular division, migration, morphogenesis and development are critical. When these molecular events are not properly regulated, disease states can develop. Tools that can allow us to better understand the specific events that, when misregulated, result in disease development can also allow us to determine better ways to combat such misregulation. Specifically, tools that could allow us to better visualize cellular processes or those that allow us to control cellular functioning in a spatiotemporal manner could present great insight into the detailed inner workings ...


M.Tb Killing By Macrophage Innate Immune Mechanisms: A Dissertation, Michelle L. Hartman Sep 2011

M.Tb Killing By Macrophage Innate Immune Mechanisms: A Dissertation, Michelle L. Hartman

GSBS Dissertations and Theses

Macrophages infected with a heavy burden of M.tb Erdman undergo a cell death that initially resembles apoptosis but quickly transitions to necrosis. Unlike the previously reported TNF dependent apoptosis induced by avirulent Mycobacterium [1], this form of macrophage cell death is not microbicidal [2]. Microbicidal effects are observed however, when the heavily infected macrophage encounters an uninfected naïve macrophage. My studies describe in part, the crosstalk between the uninfected and infected macrophage that results in the killing of the intracellular M.tb Cell contact between the two cell populations is not necessary for this killing of bacilli to occur ...


Treating Gm1 Gangliosidosis With Ex Vivo Hematopoietic Stem Cell Gene Therapy Without Using Total Body Irradiation: A Masters Thesis, Michael Whalen Aug 2011

Treating Gm1 Gangliosidosis With Ex Vivo Hematopoietic Stem Cell Gene Therapy Without Using Total Body Irradiation: A Masters Thesis, Michael Whalen

GSBS Dissertations and Theses

GM1 gangliosidosis is an autosomal recessive lysosomal storage disease, caused by a deficiency in the enzyme β-galactosidase. The disease affects the CNS, liver, kidney, heart and skeletal system, leading to severe neurodegeneration and death. We propose to treat this disorder using ex vivo hematopoietic stem cell therapy. The effectiveness of this therapy requires the recruitment of transduced donor cells to the CNS. This is only found to occur after mice are conditioned with total body irradiation, due to the increase in CNS cytokine production and blood brain barrier permeability that occurs. As the use of total body irradiation in pediatric ...


Early Detection And Treatment Of Acute Clinical Decline In Hospitalized Patients: An Observational Study Of Icu Transfers And An Assessment Of The Effectiveness Of A Rapid Response Program: A Dissertation, Tanya Lord Aug 2011

Early Detection And Treatment Of Acute Clinical Decline In Hospitalized Patients: An Observational Study Of Icu Transfers And An Assessment Of The Effectiveness Of A Rapid Response Program: A Dissertation, Tanya Lord

GSBS Dissertations and Theses

The Institute for Healthcare Improvement (IHI) has promoted implementing a RRS to provide safer care for hospitalized patients. Additionally, the Joint Commission made implementing a RRS a 2008 National Patient Safety Goal. Although mandated, the evidence to support the effectiveness of a RRS to reduce cardiac arrests on hospital medical or surgical floors and un-anticipated ICU transfers remains inconclusive, partly because of weak study designs and partly due to a failure of published studies to report all critical aspects of their intervention. This study attempted to evaluate the effectiveness and the implementation of a RRS on the two campuses of ...


Neuronal Diversification In The Postembryonic Drosophila Brain: A Dissertation, Suewei Lin Aug 2011

Neuronal Diversification In The Postembryonic Drosophila Brain: A Dissertation, Suewei Lin

GSBS Dissertations and Theses

A functional central nervous system (CNS) is composed of numerous types of neurons. Neurons are derived from a limited number of multipotent neural stem cells. Previous studies have suggested three major strategies nature uses to diversify neurons: lineage identity specification that gives an individual neural stem cell distinct identity based on its position in the developing CNS; temporal identity specification that gives neurons derived from a neural stem cell distinct identities based on their birth-order within the lineage; and binary cell fate specification that gives different identities to the two sister postmitotic neurons derived from the terminal division of a ...


Intranasal Colonization By Streptococcus Pneumoniae Induces Immunological Protection From Pulmonary And Systemic Infection: A Dissertation, Nang H. Maung Aug 2011

Intranasal Colonization By Streptococcus Pneumoniae Induces Immunological Protection From Pulmonary And Systemic Infection: A Dissertation, Nang H. Maung

GSBS Dissertations and Theses

Given that Streptococcus pneumoniae can cause life-threatening pulmonary and systemic infection, an apparent paradox is that the bacterium resides, usually harmlessly, in the nasopharynx of many people. Humoral immunity is thought to be the primary defense against serious pneumococcal infection, and we hypothesized that nasopharyngeal colonization of mice results in the generation of an antibody response that provides long-term protection against lung infection. We found that survival of of C57L/6 mice after intranasal inoculation with wild-type serotype 4 strain TIGR4 pneumococci required B cells but not T cells, suggesting that nasopharyngeal colonization elicited a protective humoral immune response. In ...


Role Of Protein Flexibility In Function, Resistance Pathways And Substrate Recognition Specificity In Hiv-1 Protease: A Dissertation, Seema Mittal Aug 2011

Role Of Protein Flexibility In Function, Resistance Pathways And Substrate Recognition Specificity In Hiv-1 Protease: A Dissertation, Seema Mittal

GSBS Dissertations and Theses

In the 30 years since the Center for Disease Control's Morbidity and Mortality Weekly Report published the first mention of what later was determined to be AIDS (Acquired immunodeficiency syndrome) and HIV (Human immunodeficiency virus) recognized as the causative pathogen, much has been done to understand this disease’s pathogenesis, development of drugs and emergence of drug resistance under selective drug therapy. Highly Active Antiretroviral Therapy (HAART), a combination of drugs that includes HIV-1 reverse transcriptase, protease, and more recently, integrase and entry inhibitors, have helped stabilize the HIV prevalence at extraordinarily high levels. Despite the recent stabilization of ...


Two Distinct Modes Of Signaling By Vascular Endothelial Growth Factor C Guide Blood And Lymphatic Vessel Patterning In Zebrafish: A Dissertation, Jacques A. Villefranc Aug 2011

Two Distinct Modes Of Signaling By Vascular Endothelial Growth Factor C Guide Blood And Lymphatic Vessel Patterning In Zebrafish: A Dissertation, Jacques A. Villefranc

GSBS Dissertations and Theses

Vascular Endothelial Growth Factor Receptor-3 (VEGFR3/Flt4) and its ligand Vegfc are necessary for development of both blood and lymphatic vasculature in vertebrates. In zebrafish, Vegfc/Flt4 signaling is essential for formation of arteries, veins, and lymphatic vessels. Interestingly, Flt4 appears to utilize distinct signaling pathways during the development of each of these vessels. To identify components of this pathway, we performed a transgenic haploid genetic screen in zebrafish that express EGFP under the control of a blood vessel specific promoter. As a result, we indentified a mutant allele of vascular endothelial growth factor c (vegfc), vegfcum18. vegfcum18 ...


Nuclear Import Of Smad: A Dissertation, Xiaochu Chen Aug 2011

Nuclear Import Of Smad: A Dissertation, Xiaochu Chen

GSBS Dissertations and Theses

Signal transduction by transforming growth factor β (TGF-β) cytokines is mediated by an evolutionarily conserved mechanism that depends on the Smad proteins to transduce an extracellular stimulus into the nucleus. In the unstimulated state, Smads spontaneously shuttle across the nuclear envelope and distribute throughout the cell. Upon TGF-β or bone morphogenetic protein (BMP) stimulation, the receptor-activated Smads are phosphorylated, assemble into complexes with Smad4, and become mostly localized in the nucleus. Such signal-induced nuclear translocation of activated Smads is essential for TGF-β–dependent gene regulation that is critical for embryonic development and homeostasis. The molecular machinery responsible for this process ...


Digital And Analog Stat5 Signaling In Erythropoiesis: A Dissertation, Ermelinda Porpiglia Aug 2011

Digital And Analog Stat5 Signaling In Erythropoiesis: A Dissertation, Ermelinda Porpiglia

GSBS Dissertations and Theses

Erythropoietin (Epo) modulates red blood cell production (erythropoiesis) by binding to its receptor and activating STAT5, a Signal Transducer and Activator of Transcription (STAT) protein implicated in both basal and stress erythropoiesis. Epo concentration in serum changes over three orders of magnitude, as it regulates basal erythropoiesis and its acceleration during hypoxic stress. However, it is not known how STAT5 translates the changes in Epo concentration into the required erythropoietic rates. We addressed this question by studying STAT5 phosphorylation, at the single cell level, in developing erythroblasts.

We divided erythroid progenitors in tissue into several flow-cytometric subsets and found that ...


Structural Studies Of The Anti-Hiv Human Protein Apobec3g Catalytic Domain: A Dissertation, Shivender Shandilya Aug 2011

Structural Studies Of The Anti-Hiv Human Protein Apobec3g Catalytic Domain: A Dissertation, Shivender Shandilya

GSBS Dissertations and Theses

HIV/AIDS is a disease of grave global importance with over 33 million people infected world-wide and nearly 2 million deaths each year. The rapid emergence of drug resistance, due to viral mutation, renders anti-retroviral drug candidates ineffective with alarming speed and regularity. Instead of targeting mutation prone viral proteins, an alternative approach is to target host proteins that interact with viral proteins and are critical for the HIV life-cycle. APOBEC3G is a host anti-HIV restriction factor that can exert tremendous negative pressure by hypermutating the viral genome and has the potential to be a promising candidate for anti-retroviral therapeutic ...


Regulation And Function Of Neuronal Nicotinic Acetylcholine Receptors In Lung Cancer: A Dissertation, Ma. Reina D. Improgo Aug 2011

Regulation And Function Of Neuronal Nicotinic Acetylcholine Receptors In Lung Cancer: A Dissertation, Ma. Reina D. Improgo

GSBS Dissertations and Theses

Lung cancer is the leading cause of cancer-related mortality worldwide. The main risk factor associated with lung cancer is cigarette smoking. Research through the years suggests that nicotine in cigarettes promotes lung cancer by activating signaling pathways that lead to cell proliferation, cell survival, angiogenesis, and metastasis. Nicotine’s cellular actions are mediated by its cognate receptors, nicotinic acetylcholine receptors (nAChRs). Here, I describe the expression levels of all known human nAChR subunit genes in both normal and lung cancer cells. Of note, the genes encoding the α5, α3, and β4 subunits (CHRNA5/A3/B4) are over-expressed in small cell ...


Asymmetric Inheritance And Post-Mitotic Fate Of Midbodies: A Dissertation, Chun-Ting Chen Aug 2011

Asymmetric Inheritance And Post-Mitotic Fate Of Midbodies: A Dissertation, Chun-Ting Chen

GSBS Dissertations and Theses

Cytokinesis is the final chapter of cell division and its last page is abscission, the physical separation of two daughter cells. During cytokinesis of vertebrate cells, two future daughter cells are connected by an intercellular bridge within which the midbody (MB) is positioned. Since becoming the focus of intense investigations on cytokinesis completion, MB is now perceived as a complicated organelle where multiple pathways for abscission are targeted and coordinated. However, whether post-mitotic midbodies, the midbody derivatives (MBds), would be retained by either daughter cell post-abscission remains unexplored. In addition, how cells manage the fate of inherited MB ...


Tyraminergic G Protein-Coupled Receptors Modulate Locomotion And Navigational Behavior In C. Elegans: A Dissertation, Jamie L. Donnelly Aug 2011

Tyraminergic G Protein-Coupled Receptors Modulate Locomotion And Navigational Behavior In C. Elegans: A Dissertation, Jamie L. Donnelly

GSBS Dissertations and Theses

An animal’s ability to navigate through its natural environment is critical to its survival. Navigation can be slow and methodical such as an annual migration, or purely reactive such as an escape response. How sensory input is translated into a fast behavioral output to execute goal oriented locomotion remains elusive. In this dissertation, I aimed to investigate escape response behavior in the nematode C. elegans. It has been shown that the biogenic amine tyramine is essential for the escape response. A tyramine-gated chloride channel, LGC-55, has been revealed to modulate suppression of head oscillations and reversal behavior in response ...


Cooperativity In Mammalian Rna Silencing: A Dissertation, Jennifer A. Broderick Jul 2011

Cooperativity In Mammalian Rna Silencing: A Dissertation, Jennifer A. Broderick

GSBS Dissertations and Theses

Argonaute proteins are the core component of an RNA silencing complex. The human genome encodes four Argonaute paralogs –Ago1, Ago2, Ago3 and Ago4– proteins that are guided to target mRNAs by microRNAs. More than 500 miRNAs are conserved between mammals, and each microRNA can repress hundreds of genes, regulating almost every cellular process. We still do not fully understand the molecular mechanisms by which miRNAs regulate gene expression. Although we understand many aspects of microRNA biogenesis and formation of the RNA-induced silencing complex, much less is known about the subsequent steps leading to target mRNA regulation.

Mammalian microRNAs rarely have ...


Use Of Multinational Registries To Assess And Compare Outcomes Of Patients With An Acute Coronary Syndrome: A Dissertation, Hamza H. Awad Jul 2011

Use Of Multinational Registries To Assess And Compare Outcomes Of Patients With An Acute Coronary Syndrome: A Dissertation, Hamza H. Awad

GSBS Dissertations and Theses

Background
Acute coronary syndromes (ACS) are a major cause of mortality and morbidity in the developed world. By 2020, ACS will be the leading cause of morbidity and mortality worldwide, largely due to substantial increases in ACS burden in developing countries. The developing world has been under-represented in international ACS registries. The Arabian Gulf area is a part of the developing world where little is known about the epidemiology of ACS. The first aim of the dissertation is to compare ACS patient characteristics, current practice patterns, and in-hospital outcomes in the Arabian Gulf area to a large multinational sample. Patients ...


Chromosome-Biased Binding And Function Of C. Elegans Drm Complex, And Its Role In Germline Sex-Silencing: A Dissertation, Tomoko M. Tabuchi Jul 2011

Chromosome-Biased Binding And Function Of C. Elegans Drm Complex, And Its Role In Germline Sex-Silencing: A Dissertation, Tomoko M. Tabuchi

GSBS Dissertations and Theses

DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in the cell cycle and cancer. Recent work has unveiled a new aspect of DRM function in regulating genes involved in development and differentiation. These studies, however, were performed with cultured cells and a genome-wide study involving intact organisms undergoing active proliferation and differentiation was lacking. Our goal was to extend the knowledge of the role of DRM in gene regulation through development and in multiple tissues. To accomplish this, we employed genomic approaches to determine genome-wide targets of DRM using ...


Global Dna Demethylation During Erythropoiesis: A Dissertation, Jeffrey R. Shearstone Jul 2011

Global Dna Demethylation During Erythropoiesis: A Dissertation, Jeffrey R. Shearstone

GSBS Dissertations and Theses

In the mammalian genome, 5‟-CpG-3‟ dinucleotides are frequently methylated, correlating with transcriptional silencing. Genome-wide waves of demethylation are thought to occur only twice during development, in primordial germ cells and in the pre-implantation embryo. They are followed by de novo methylation, setting up a pattern that is inherited throughout development. No global methylation changes are thought to occur during further somatic development, although methylation does alter at gene-specific loci, contributing to tissue-specific patterns of gene expression. Here we studied DNA methylation in differentiating mouse erythroblasts in vivo using several approaches including genomic-scale, reduced representation bisulfite sequencing (RRBS). Surprisingly, demethylation ...


Biomimetic Synthetic Tissue Scaffolds For Bone Regeneration: A Dissertation, Tera M. Filion Potts Jul 2011

Biomimetic Synthetic Tissue Scaffolds For Bone Regeneration: A Dissertation, Tera M. Filion Potts

GSBS Dissertations and Theses

Injury to bone is one of the most prevalent and costly medical conditions. Clinical treatment of volumetric bone loss or hard-to-heal bony lesions often requires the use of proper bone grafting materials, with or without adjuvant anabolic therapeutics. Despite significant problems associated with autografting (donor site morbidity, limited supplies) and allografting (disease transmissions, high graft failure rates) procedures, synthetic bone grafts remain the least utilized clinically. Existing synthetic orthopaedic biomaterials rarely possess a combination of bone-like structural and biochemical properties required for robust osteointegration, scalable and user-friendly characteristics indispensable for successful clinical translations. This thesis tests the hypothesis that by ...


Regulation Of Runx Proteins In Human Cancers: A Dissertation, Sandhya Pande Jul 2011

Regulation Of Runx Proteins In Human Cancers: A Dissertation, Sandhya Pande

GSBS Dissertations and Theses

Runt related transcription factors (Runx) play an important role in mammalian development by regulating the expression of key genes involved in cell proliferation, differentiation and growth. The work described in this thesis details the mechanisms by which the activity of two members of this family are regulated in human cells. Chapter One provides a brief introduction of Runx transcription factors.

Chapter Two describes the regulation of Runx2 protein by the PI3 kinase/Akt pathway in human breast cancer cells. The PI3 kinase/Akt pathway is one of the major signal transduction pathways through which growth factors influence cell proliferation and ...


Dissection Of Α6Β4 Integrin-Dependent Signaling And Breast Carcinoma Invasion: A Dissertation, Xiaoqing Yang Jul 2011

Dissection Of Α6Β4 Integrin-Dependent Signaling And Breast Carcinoma Invasion: A Dissertation, Xiaoqing Yang

GSBS Dissertations and Theses

Breast cancer is one of the most prevalent cancers in the world. Each year, over 400,000 women die from breast cancer world wide and metastasis is the main cause of their mortality. Tumor cell invasion into the adjacent tissue is the first step in the multistep process of cancer metastasis and it involves multiple protein changes. The α6β4 integrin, a transmembrane heterodimeric laminin receptor is associated with poor prognosis in many tumor types, including breast cancer. Src family kinase (SFK) activity is elevated in many cancers and this activity also correlates with invasive tumor behavior. The α6β4 integrin can ...