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Functional Characterization Of Novel Pfn1 Mutations Causative For Familial Amyotrophic Lateral Sclerosis: A Dissertation, Chi-Hong Wu Dec 2015

Functional Characterization Of Novel Pfn1 Mutations Causative For Familial Amyotrophic Lateral Sclerosis: A Dissertation, Chi-Hong Wu

GSBS Dissertations and Theses

Amyotrophic lateral sclerosis (ALS) is a progressive adult neurodegenerative disease that causes death of both upper and lower motor neurons. Approximately 90 percent of ALS cases are sporadic (SALS), and 10 percent are inherited (FALS). Mutations in the PFN1 gene have been identified as causative for one percent of FALS. PFN1 is a small actin-binding protein that promotes actin polymerization, but how ALS-linked PFN1 mutations affect its cognate functions or acquire gain-of-function toxicity remains largely unknown.

To elucidate the contribution of ALS-linked PFN1 mutations to neurodegeneration, we have characterized these mutants in both mammalian cultured cells and Drosophila models. In ...


Hepatitis C Virus: Structural Insights Into Protease Inhibitor Efficacy And Drug Resistance: A Dissertation, Djade I. Soumana Dec 2015

Hepatitis C Virus: Structural Insights Into Protease Inhibitor Efficacy And Drug Resistance: A Dissertation, Djade I. Soumana

GSBS Dissertations and Theses

The Hepatitis C Virus (HCV) is a global health problem as it afflicts an estimated 170 million people worldwide and is the major cause of viral hepatitis, cirrhosis and liver cancer. HCV is a rapidly evolving virus, with 6 major genotypes and multiple subtypes. Over the past 20 years, HCV therapeutic efforts have focused on identifying the best-in-class direct acting antiviral (DAA) targeting crucial components of the viral lifecycle, The NS3/4A protease is responsible for processing the viral polyprotein, a crucial step in viral maturation, and for cleaving host factors involved in activating immunity. Thus targeting the NS3/4A ...


Single-Molecule Imaging Reveals That Argonaute Re-Shapes The Properties Of Its Nucleic Acid Guides: A Dissertation, William E. Salomon Dec 2015

Single-Molecule Imaging Reveals That Argonaute Re-Shapes The Properties Of Its Nucleic Acid Guides: A Dissertation, William E. Salomon

GSBS Dissertations and Theses

Small RNA silencing pathways regulate development, viral defense, and genomic integrity in all kingdoms of life. An Argonaute (Ago) protein, guided by a tightly bound, small RNA or DNA, lies at the core of these pathways. Argonaute uses its small RNA or DNA to find its target sequences, which it either cleaves or stably binds, acting as a binding scaffold for other proteins. We used Co-localization Single-Molecule Spectroscopy (CoSMoS) to analyze target binding and cleavage by Ago and its guide. We find that both eukaryotic and prokaryotic Argonaute proteins re-shape the fundamental properties of RNA:RNA, RNA:DNA, and DNA ...


Gene Therapy For Amyotrophic Lateral Sclerosis: An Aav Delivered Artifical Microrna Against Human Sod1 Increases Survival And Delays Disease Progression Of The Sod1G93a Mouse Model: A Dissertation, Lorelei I. Stoica Dec 2015

Gene Therapy For Amyotrophic Lateral Sclerosis: An Aav Delivered Artifical Microrna Against Human Sod1 Increases Survival And Delays Disease Progression Of The Sod1G93a Mouse Model: A Dissertation, Lorelei I. Stoica

GSBS Dissertations and Theses

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of motor neurons, resulting in progressive muscle weakness, atrophy, paralysis and death within five years of diagnosis. About ten percent of cases are inherited, of which twenty percent are due to mutations in the superoxide dismutase 1 (SOD1) gene. Since the only FDA approved ALS drug prolongs survival by just a few months, new therapies for this disease are needed. Experiments in transgenic ALS mouse models have shown that decreasing levels of mutant SOD1 protein alters and in some cases entirely prevents disease progression. We explored this potential ...


Gender Differences In Choice Of Procedure And Case Fatality Rate For Elderly Patients With Acute Cholecystitis: A Masters Thesis, Courtney E. Collins Dec 2015

Gender Differences In Choice Of Procedure And Case Fatality Rate For Elderly Patients With Acute Cholecystitis: A Masters Thesis, Courtney E. Collins

GSBS Dissertations and Theses

Background: Treatment decisions for elderly patients with gallbladder pathology are complex. Little is known about what factors go into treatment decisions in this population. We used Medicare data to examine gender-based differences in the use of cholecystectomy vs. cholecystostomy tube placement in elderly patients with acute cholecystitis.

Methods: We queried a 5% random sample of Medicare data (2009-2011) for patients >65 admitted for acute cholecystitis (by ICD-9 code) who subsequently underwent a cholecystectomy and/or cholecystostomy tube placement. Demographic information (age, race), clinical characteristics (Elixhauser index, presence of biliary pathology), and hospital outcomes (case fatality rate, length of stay, need ...


Diet Quality And Evening Snacking In Relation To Sleep Duration And Quality Among Women With Young Children: A Dissertation, Rui Sherry Xiao Nov 2015

Diet Quality And Evening Snacking In Relation To Sleep Duration And Quality Among Women With Young Children: A Dissertation, Rui Sherry Xiao

GSBS Dissertations and Theses

Background: Mothers’ diets impact their health and the health of their children, but diet quality is suboptimal among women with young children. Evening snacking among women with young children, especially consumption of high-calorie, high-carbohydrate snacks, may impact overall diet quality and glucose metabolism. Short sleep duration and poor sleep quality may be potential risk factors. We examined whether sleep duration and poor sleep quality were associated with diet quality and evening snacking among women with young children.

Methods: Data were from the National Health and Nutrition Examination Survey (NHANES) 2005-2012, nationally representative cross-sectional surveys of noninstitutionalized U.S. population. Eligible ...


The Epithelial Transmembrane Protein Perp Is Required For Inflammatory Responses To S. Typhimurium Infection: A Dissertation, Kelly N. Hallstrom Oct 2015

The Epithelial Transmembrane Protein Perp Is Required For Inflammatory Responses To S. Typhimurium Infection: A Dissertation, Kelly N. Hallstrom

GSBS Dissertations and Theses

Salmonella enterica subtype Typhimurium (S. Typhimurium) is one of many non-typhoidal Salmonella enterica strains responsible for over one million cases of salmonellosis in the United States each year. These Salmonella strains are also a leading cause of diarrheal disease in developing countries. Nontyphoidal salmonellosis induces gastrointestinal distress that is characterized histopathologically by an influx of polymorphonuclear leukocytes (PMNs), the non-specific effects of which lead to tissue damage and contribute to diarrhea.

Prior studies from our lab have demonstrated that the type III secreted bacterial effector SipA is a key regulator of PMN influx during S. Typhimurium infection and that its ...


Roles Of Protein Arginine Methyltransferase 7 And Jumonji Domain-Containing Protein 6 In Adipocyte Differentiation: A Dissertation, Yu-Jie Hu Oct 2015

Roles Of Protein Arginine Methyltransferase 7 And Jumonji Domain-Containing Protein 6 In Adipocyte Differentiation: A Dissertation, Yu-Jie Hu

GSBS Dissertations and Theses

Regulation of gene expression comprises a wide range of mechanisms that control the abundance of gene products in response to environmental and developmental changes. These biological processes can be modulated by posttranslational modifications including arginine methylation. Among the enzymes that catalyze the methylation, protein arginine methyltransferase 7 (PRMT7) is known to modify histones to repress gene expression. Jumonji domain-containing protein 6 (JMJD6) is a putative arginine demethylase that potentially antagonize PRMT7. However, the biological significance of these enzymes is not well understood. This thesis summarizes the investigation of both PRMT7 and JMJD6 in cell culture models for adipocyte differentiation. The ...


Insights Into Melanocyte Regeneration And Melanoma Initiation Using The Zebrafish Model System: A Dissertation, Sharanya Iyengar Oct 2015

Insights Into Melanocyte Regeneration And Melanoma Initiation Using The Zebrafish Model System: A Dissertation, Sharanya Iyengar

GSBS Dissertations and Theses

During regeneration, cells must coordinate proliferation and differentiation to rebuild tissues that are lost. Understanding how source cells execute the regeneration process has been a longstanding goal in regenerative biology with implications in wound healing and cell replacement therapies. Melanocytes are pigment-producing cells in the skin of vertebrates that can be lost during hair graying, injury and disease-related depigmentation. Melanoma is an aggressive skin cancer that develops from melanocytes, and it is hypothesized that melanoma cells have properties that are similar to melanocyte stem cells.

To gain insight into melanocyte regeneration we set out to identify the source of regeneration ...


The Role Of Vta Gabaergic Nicotinic Acetylcholine Receptors Containing The Α4 Subunit In Nicotine Dependence: A Dissertation, Jennifer Ngolab Oct 2015

The Role Of Vta Gabaergic Nicotinic Acetylcholine Receptors Containing The Α4 Subunit In Nicotine Dependence: A Dissertation, Jennifer Ngolab

GSBS Dissertations and Theses

Nicotine dependence is hypothesized to be due to neuroadaptations that ultimately drive compulsive nicotine use. The studies in this thesis aim to understand how the “upregulation” of nicotinic acetylcholine receptors (nAChRs) caused by chronic exposure to nicotine contributes to nicotine reward and nicotine withdrawal. Previous studies have shown that chronic nicotine induces upregulation of nAChRs containing the α4 subunit (α4* nAChR) within the Ventral Tegmental Area (VTA), a brain region critical for the rewarding properties of all illicit drugs. Curiously, α4* nAChR upregulation occurs specifically in the inhibitory GABAergic neuronal subpopulation of the VTA. To determine if increased expression and ...


Regulation Of Metabolism By Hepatic Oxphos: A Dissertation, Thomas E. Akie Oct 2015

Regulation Of Metabolism By Hepatic Oxphos: A Dissertation, Thomas E. Akie

GSBS Dissertations and Theses

Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent issue in the modern world, predisposing patients to serious pathology such as cirrhosis and hepatocellular carcinoma. Mitochondrial dysfunction, and in particular, diminished hepatic oxidative phosphorylation (OXPHOS) capacity, have been observed in NAFLD livers, which may participate in NAFLD pathogenesis.

To examine the role of OXPHOS in NAFLD, we generated a model of enhanced hepatic OXPHOS using mice with liver-specific transgenic expression of LRPPRC, a protein which activates mitochondrial transcription and augments OXPHOS capacity. When challenged with high-fat feeding, mice with enhanced hepatic OXPHOS were protected from the development of liver steatosis ...


Exploring The Role Of Fus Mutants From Stress Granule Incorporation To Nucleopathy In Amyotrophic Lateral Sclerosis: A Dissertation, Hae Kyung Ko Sep 2015

Exploring The Role Of Fus Mutants From Stress Granule Incorporation To Nucleopathy In Amyotrophic Lateral Sclerosis: A Dissertation, Hae Kyung Ko

GSBS Dissertations and Theses

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by preferential motor neuron death in the brain and spinal cord. The rapid disease progression results in death due to respiratory failure, typically within 3-5 years after disease onset. While ~90% of cases occur sporadically, remaining 10% of ALS cases show familial inheritance, and the number of genes linked to ALS has increased dramatically over the past decade.

FUS/TLS (Fused in Sarcoma/ Translocated to liposarcoma) is a nucleic acid binding protein that may regulate several cellular functions, including RNA splicing, transcription, DNA damage repair and microRNA biogenesis. More than ...


Investigating The Effects Of Mutant Fus On Stress Response In Amyotrophic Lateral Sclerosis: A Thesis, Laura J. Kaushansky Aug 2015

Investigating The Effects Of Mutant Fus On Stress Response In Amyotrophic Lateral Sclerosis: A Thesis, Laura J. Kaushansky

GSBS Dissertations and Theses

During stress, eukaryotes regulate protein synthesis in part through formation of cytoplasmic, non-membrane-bound complexes called stress granules (SGs). SGs transiently store signaling proteins and stalled translational complexes in response to stress stimuli (e.g. oxidative insult, DNA damage, temperature shifts and ER dysfunction). The functional outcome of SGs is proper translational regulation and signaling, allowing cells to overcome stress.

The fatal motor neuron disease Amyotrophic Lateral Sclerosis (ALS) develops in an age-related manner and is marked by progressive neuronal death, with cytoplasmic protein aggregation, excitotoxicity and increased oxidative stress as major hallmarks. Fused in Sarcoma/Translocated in Liposarcoma (FUS) is ...


Exploring New Strategies To Overcome Resistance In Glioblastoma Multiforme: A Dissertation, Yulian P. Ellis Aug 2015

Exploring New Strategies To Overcome Resistance In Glioblastoma Multiforme: A Dissertation, Yulian P. Ellis

GSBS Dissertations and Theses

Glioblastoma multiforme (GBM) tumors are highly malignant in nature and despite an aggressive therapy regimen, long–term survival for glioma patients is uncommon as cells with intrinsic or acquired resistance to treatment repopulate the tumor. This creates the need to investigate new therapies for enhancing GBM treatment outside of the standard of care, which includes Temozolomide (TMZ). Our lab focused on two novel strategies to overcome resistance in GBMs. In our first approach, the cellular responses of GBM cell lines to two new TMZ analogues, DP68 and DP86, are reported. The efficacy of these compounds was independent of DNA repair ...


Attention Deficit/Hyperactivity Disorder, Screen Time, Physical Activity, And Diet Quality: A Dissertation, Carol Curtin Jul 2015

Attention Deficit/Hyperactivity Disorder, Screen Time, Physical Activity, And Diet Quality: A Dissertation, Carol Curtin

GSBS Dissertations and Theses

Background. Emerging evidence suggests that youth with attention deficit/hyperactivity disorder (ADHD) may engage in sub-optimal health behaviors including high levels of screen time, low physical activity participation, and consumption of poor diets. These are independent risk factors for adverse health outcomes, and health-related behavior patterns established in childhood can track into adulthood. Thus, identifying and addressing dietary and physical activity habits in sub-populations of youth have important implications for health over the lifespan. The specific aims of this dissertation were to: (1) compare screen time between youth with and without ADHD and to assess its relationship to ADHD symptomatology ...


Jun Kinases In Hematopoiesis, And Vascular Development And Function: A Dissertation, Kasmir Ramo Jul 2015

Jun Kinases In Hematopoiesis, And Vascular Development And Function: A Dissertation, Kasmir Ramo

GSBS Dissertations and Theses

Arterial occlusive diseases are major causes of morbidity and mortality in industrialized countries and represent a huge economic burden. The extent of the native collateral circulation is an important determinant of blood perfusion restoration and therefore the severity of tissue damage and functional impairment that ensues following arterial occlusion. Understanding the mechanisms responsible for collateral artery development may provide avenues for therapeutic intervention. Here, we identify a critical requirement for mixed lineage kinase (MLK) – cJun-NH2-terminal kinase (JNK) signaling in vascular morphogenesis and native collateral artery development. We demonstrate that Mlk2-/-Mlk3-/- mice or mice with compound JNK-deficiency in the vascular ...


Identifying, Targeting, And Exploiting A Common Misfolded, Toxic Conformation Of Sod1 In Als: A Dissertation, Melissa S. Rotunno Jun 2015

Identifying, Targeting, And Exploiting A Common Misfolded, Toxic Conformation Of Sod1 In Als: A Dissertation, Melissa S. Rotunno

GSBS Dissertations and Theses

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a loss of voluntary movement over time, leading to paralysis and death. While 10% of ALS cases are inherited or familial (FALS), the majority of cases (90%) are sporadic (SALS) with unknown etiology. Approximately 20% of FALS cases are genetically linked to a mutation in the anti-oxidizing enzyme, superoxide dismutase (SOD1). SALS and FALS are clinically indistinguishable, suggesting a common pathogenic mechanism exists for both types. Since such a large number of genetic mutations in SOD1 result in FALS (>170), it is reasonable to suspect that non-genetic modifications to SOD1 ...


Sentinel Lymph Node Biopsy In Elderly Patients With Intermediate Thickness Melanoma: A Masters Thesis, Kate H. Dinh May 2015

Sentinel Lymph Node Biopsy In Elderly Patients With Intermediate Thickness Melanoma: A Masters Thesis, Kate H. Dinh

GSBS Dissertations and Theses

Background: A landmark study suggested that wide excision of intermediate-thickness melanoma with sentinel lymph node biopsy (SLNB) and subsequent completion lymph node dissection (CLND) for regional disease may improve prognostication and disease-free survival (DFS) compared with those undergoing wide excision alone. However, these benefits were relatively small and not associated with an improvement in disease-specific survival (DSS). It remains unknown if SLNB and subsequent treatments are beneficial in elderly patients who have a decreased overall (OS) due to other causes.

Methods: Adults ≥ 70 years of age, who underwent surgical intervention for intermediate-thickness cutaneous melanoma from 2000-2013 were identified from a ...


Cathosis: Cathepsins In Particle-Induced Inflammatory Cell Death: A Dissertation, Gregory M. Orlowski May 2015

Cathosis: Cathepsins In Particle-Induced Inflammatory Cell Death: A Dissertation, Gregory M. Orlowski

GSBS Dissertations and Theses

Sterile particles underlie the pathogenesis of numerous inflammatory diseases. These diseases can often become chronic and debilitating. Moreover, they are common, and include silicosis (silica), asbestosis (asbestos), gout (monosodium urate), atherosclerosis (cholesterol crystals), and Alzeihmer’s disease (amyloid Aβ). Central to the pathology of these diseases is a repeating cycle of particle-induced cell death and inflammation. Macrophages are the key cellular mediators thought to drive this process, as they are especially sensitive to particle-induced cell death and they are also the dominant producers of the cytokine responsible for much of this inflammation, IL-1β. In response to cytokines or microbial cues ...


Language Proficiency, Citizenship, And Food Insecurity Among Predominantly Immigrant Caribbean Latinos In Massachusetts: A Masters Thesis, Tariana V. Little Apr 2015

Language Proficiency, Citizenship, And Food Insecurity Among Predominantly Immigrant Caribbean Latinos In Massachusetts: A Masters Thesis, Tariana V. Little

GSBS Dissertations and Theses

BACKGROUND: Latinos report higher food insecurity than the national average, and food insecurity has been associated with adverse health outcomes wherein Latinos experience disparities. This study quantified the independent effects of language-speaking proficiency and citizenship on increased food insecurity among a predominantly immigrant Caribbean Latino sample in Lawrence, Massachusetts.

METHODS: The analytic sample comprised 574 participants aged 21-83 who visited a community health center in 2011-2013. Food insecurity was assessed via the 6-item US Household Food Security Survey. Multivariable logistic modeling (adjusted for self-reported age group, gender, education, and marital status) examined the independent associations between language proficiency and citizenship ...


Causal Inference Methods For Assessing Neurodevelopment In Children Following Prenatal Exposure To Triptan Medications: A Dissertation, Mollie E. Wood Apr 2015

Causal Inference Methods For Assessing Neurodevelopment In Children Following Prenatal Exposure To Triptan Medications: A Dissertation, Mollie E. Wood

GSBS Dissertations and Theses

Background: Migraine headache is a chronic pain condition that affects 20% of women of reproductive age, and is often treated with triptans. Triptans are serotonin 1B, 1D, and 1F receptor agonists that act as vasoconstrictors and inhibitors of the trigeminal cervical complex as well as peripheral neurons; they cross the blood brain barrier and placenta, and as such are plausible neurodevelopmental teratogens. No studies have examined risk of neurodevelopmental problems in children with prenatal triptan exposure. This dissertation had three aims: (1) to examine risk of behavioral problems in children using in the presence of time-varying confounding by concomitant medication ...


Latent Variable Approaches For Understanding Heterogeneity In Depression: A Dissertation, Christine M. Ulbricht Apr 2015

Latent Variable Approaches For Understanding Heterogeneity In Depression: A Dissertation, Christine M. Ulbricht

GSBS Dissertations and Theses

Background: Major depression is one of the most prevalent, disabling, and costly illnesses worldwide. Despite a 400% increase in antidepressant medication use since 1988, fewer than half of treated depression patients experience a clinically meaningful reduction in symptoms and uncertainty exists regarding how to successfully obtain symptom remission. Identifying homogenous subgroups based on clinically observable characteristics could improve the ability to efficiently predict who will benefit from which treatments.

Methods: Latent class analysis and latent transition analysis (LTA) were applied to data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study to explore how to efficiently identify subgroups ...


Hospital Treatment Practices, 30-Day Hospital Readmissions, And Long-Term Prognosis In Patients Hospitalized With Acute Myocardial Infarction: A Dissertation, Han-Yang Chen Apr 2015

Hospital Treatment Practices, 30-Day Hospital Readmissions, And Long-Term Prognosis In Patients Hospitalized With Acute Myocardial Infarction: A Dissertation, Han-Yang Chen

GSBS Dissertations and Theses

Background: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the U.S. Acute myocardial infarction (AMI), with or without ST-segment elevation, is a common presentation of coronary heart disease and affected more than 800,000 American adults in 2010. The overall goal of this dissertation was to examine decade-long trends in the extent of delay in the receipt of a primary percutaneous coronary intervention (PCI) among patients hospitalized with ST-segment elevation myocardial infarction (STEMI), 30-day hospital readmission rates in patients having survived an AMI, and multiple decade long trends in 1-year post-hospital all-cause mortality, as well ...


Yeast Upf1 Associates With Ribosomestranslating Mrna Coding Sequences Upstream Of Normal Termination Codons: A Dissertation, Ei Ei Min Apr 2015

Yeast Upf1 Associates With Ribosomestranslating Mrna Coding Sequences Upstream Of Normal Termination Codons: A Dissertation, Ei Ei Min

GSBS Dissertations and Theses

Nonsense-mediated mRNA decay (NMD) specifically targets mRNAs with premature translation termination codons for rapid degradation. NMD is a highly conserved translation-dependent mRNA decay pathway, and its core Upf factors are thought to be recruited to prematurely terminating mRNP complexes, possibly through the release factors that orchestrate translation termination. Upf1 is the central regulator of NMD and recent studies have challenged the notion that this protein is specifically targeted to aberrant, nonsense-containing mRNAs. Rather, it has been proposed that Upf1 binds to most mRNAs in a translation-independent manner. In this thesis, I investigated the nature of Upf1 association with its substrates ...


Rapid Access To Perinatal Psychiatric Care In Depression (Rappid): A Master’S Thesis, Nancy Byatt Apr 2015

Rapid Access To Perinatal Psychiatric Care In Depression (Rappid): A Master’S Thesis, Nancy Byatt

GSBS Dissertations and Theses

Depression is the leading cause of disability among women of reproductive age worldwide. Upwards of 1 in 5 women suffer from perinatal depression. This condition has deleterious effects on several birth outcomes, infant attachment, and children’s behavior/development. Maternal suicide causes 20% of postpartum deaths in depressed women. Although the vast majority of perinatal women are amenable to being screened for depression, screening alone does not improve treatment rates or patient outcomes. Obstetrics/Gynecology (Ob/Gyn) clinics need supports in place to adequately address depression in their patient populations. The primary goal of this thesis is to develop, refine ...


Dissecting The Role Of A Lncrna And Involvement Of Plasmodium Infections In The Innate Immune Response: A Dissertation, Jennie Chan Apr 2015

Dissecting The Role Of A Lncrna And Involvement Of Plasmodium Infections In The Innate Immune Response: A Dissertation, Jennie Chan

GSBS Dissertations and Theses

The innate immune system is a multicomponent response governed by intricate mechanisms of induction, regulation and resolution to elicit antimicrobial defenses. In recent years, the complexity of eukaryotic transcriptomes has become the subject of intense scrutiny and curiosity. It has been established, that RNA polymerase II (RNAPII) transcribes hundreds to thousands of long noncoding RNAs (lncRNAs), often in a stimulus and cell-type specific manner. However, the functional significance of these transcripts has been particularly controversial. While the number of identified lncRNAs is growing, our understanding of how lncRNAs themselves regulate other genes is quite limited. In chapter 2, a novel ...


Subtle Controllers: Micrornas Drive Pancreatic Tumorigenesis And Progression: A Dissertation, Brian J. Quattrochi Apr 2015

Subtle Controllers: Micrornas Drive Pancreatic Tumorigenesis And Progression: A Dissertation, Brian J. Quattrochi

GSBS Dissertations and Theses

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies in the United States, with an average five-year survival rate of just 6.7%. One unifying aspect of PDAC is mutational activation of the KRAS oncogene, which occurs in over 90% of PDAC. Therefore, inhibiting KRAS function is likely an effective therapeutic strategy for this disease, and current research in our lab and others is focused on identifying downstream effectors of KRAS signaling that may be therapeutic targets. miRNAs are powerful regulators of gene expression that can behave as oncogenes or tumor suppressors. Dysregulation of miRNA expression is commonly observed ...


Use Of Opioids For Pain Management In Nursing Homes: A Dissertation, Camilla B. Pimentel Apr 2015

Use Of Opioids For Pain Management In Nursing Homes: A Dissertation, Camilla B. Pimentel

GSBS Dissertations and Theses

Nursing homes are an essential yet understudied provider of cancer-related care for those with complex health needs. Nine percent of nursing home residents have a cancer diagnosis at admission, and it is estimated that one-third of them experience pain on a daily basis. Although pain management is an essential component of disease treatment, few studies have evaluated analgesic medication use among adults with cancer in this setting. Use of opioids, which are the mainstay of pain management in older adults because of their effectiveness in controlling moderate to severe pain, may be significantly related to coverage by the Medicare Part ...


Predicting Other Cause Mortality Risk For Older Men With Localized Prostate Cancer: A Dissertation, Daniel M. Frendl Mar 2015

Predicting Other Cause Mortality Risk For Older Men With Localized Prostate Cancer: A Dissertation, Daniel M. Frendl

GSBS Dissertations and Theses

Background: Overtreatment of localized prostate cancer (PCa) is a concern as many men die of other causes prior to experiencing a treatment benefit. This dissertation characterizes the need for assessing other cause mortality (OCM) risk in older men with PCa and informs efforts to identify patients most likely to benefit from definitive PCa treatment.

Methods: Using the linked Surveillance Epidemiology and End Results-Medicare Health Outcomes Survey database, 2,931 men (mean age=75) newly diagnosed with clinical stage T1a-T3a PCa from 1998-2009 were identified. Survival analysis methods were used to compare observed 10-year OCM by primary treatment type. Age and ...


Function And Regulation Of The Α6 Integrins In Mammary Epithelial Biology And Breast Cancer: A Dissertation, Cheng Chang Feb 2015

Function And Regulation Of The Α6 Integrins In Mammary Epithelial Biology And Breast Cancer: A Dissertation, Cheng Chang

GSBS Dissertations and Theses

Integrins have the ability to impact major aspects of epithelial biology including adhesion, migration, invasion, signaling and differentiation, as well as the formation and progression of cancer (Hynes 2002; Srichai and Zent 2010; Anderson et al. 2014). This thesis focuses on how integrins are regulated and function in the context of mammary epithelial biology and breast cancer with a specific focus on the α6 integrin heterodimers (α6β1 and α6β4). These integrins function primarily as receptors for the laminin family of extracellular matrix (ECM) proteins and they have been implicated in mammary gland biology and breast cancer (Friedrichs et al. 1995 ...