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The Unfolded Protein Response And Calcium Dysregulation In Autosomal Dominant Retinitis Pigmentosa Animal Models., Vishal Madhukar Shinde Jan 2015

The Unfolded Protein Response And Calcium Dysregulation In Autosomal Dominant Retinitis Pigmentosa Animal Models., Vishal Madhukar Shinde

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The photoreceptor cell death in autosomal dominant retinitis pigmentosa (ADRP) is associated with molecular changes that occur due to mutations in a specific gene. S334ter RHO and P23H RHO are two ADRP rat models expressing mutant rhodopsin. The unfolded protein response (UPR) is a cellular stress response involved in the pathophysiology of several retinal disorders including P23H RHO rats. Considering our previous findings, we started our investigation by examining the status of UPR in S334ter RHO rats. As UPR tightly regulates several signaling pathways, we further studied whether UPR activation in S334ter and P23H RHO retina is accompanied by the …

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The Multifactorial Roles Of The Cytokines Il-21 And Il-22 In Mediating Host Defense Against Enteropathogenic Infection, Daniel James Silberger Jan 2015

The Multifactorial Roles Of The Cytokines Il-21 And Il-22 In Mediating Host Defense Against Enteropathogenic Infection, Daniel James Silberger

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Enteropathogenic strains of Escherichia coli are a major public health concern, causing diarrhea and mortality particularly among infants and children in developing countries. Citrobacter rodentium is a murine intestinal pathogen that models pathogenic E. coli infection. Both innate and adaptive immune cells contribute to the clearance of C. rodentium. In particular, B cells and CD4+ T cells but not CD8+ T cells are required for protection during a primary infection with C. rodentium. In addition, T cell-dependent antibody responses are required for clearance. Th17 cells are a major CD4+ T cell population that accumulates in the large intestine during C. …

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Computational Modelling And Surface Charachterization Of Interface In Polymer Composites By Atomic Force Microscopy, Daljeet Kumar Singh Jan 2015

Computational Modelling And Surface Charachterization Of Interface In Polymer Composites By Atomic Force Microscopy, Daljeet Kumar Singh

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Polymer composites are used in numerous industries due to their high specific strength and high specific stiffness. Such composites have markedly different properties than both the reinforcement and the matrix. Of the several factors which govern the final property of the composite, the interface is the single most factor that influences the stress transfer mechanism from the fiber to the matrix. The interface bond strength is also influenced by the surface treatments applied to the fiber during spinning and weaving. The present study is an effort to characterize and model the fiber-matrix interface in polymer matrix composites. Finite element models …

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Comparison Of Gut Microbiomes In Laboratory Cultured Sea Urchins Revealing Selective Attributes Of Microbial Composition Based Upon Their Feed And Surroundings, Joseph Antoine Hakim Jan 2015

Comparison Of Gut Microbiomes In Laboratory Cultured Sea Urchins Revealing Selective Attributes Of Microbial Composition Based Upon Their Feed And Surroundings, Joseph Antoine Hakim

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Bacteria residing in the gastrointestinal tract play important roles in digestive physiology and host health. The advent of NextGen sequencing and bioinformatics has made it possible to establish taxonomic profiles with highest coverage, and map these microbes in the gut ecosystem. Although extensively studied in the context of human health, understanding the microbial profiles associated with other organisms will elucidate the roles of the microbial inhabitants to their respective hosts and environment. The microbes of the sea urchin gut have been linked to digestion, processing, and extraction of nutrients from ingesta while within the gut, and have also been implicated …

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Obesity Weighs Down Memory: Emerging Insights Into The Epigentic Basis Of Obesity-Induced Memory Impairment In Adult Mice, Frankie Darryn Heyward Jan 2015

Obesity Weighs Down Memory: Emerging Insights Into The Epigentic Basis Of Obesity-Induced Memory Impairment In Adult Mice, Frankie Darryn Heyward

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A preponderance of evidence has established that obesity contributes to memory impairments in mid-age adults. Empirical evidence has revealed that diet-induced obesity contributes to memory impairments in adult rodents. Precisely how obesity disrupts memory remains an open question. Bourgeoning data indicate that molecular epigenetic mechanisms mediate the changes in gene transcription that are necessary for hippocampus-dependent memory consolidation. Epigenetic mechanisms, such as DNA methylation, stably regulate gene expression without affecting the DNA sequence. Moreover, DNA methylation of memory-related genes with in the hippocampus is indispensible for memory formation. There is recent evidence of obesity-induced aberrantions in DNA methylation both peripherally …

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Statistical Methodology To Improve The Understanding Of Dna Methylation Data, Lindsay Leigh Waite Jones Jan 2015

Statistical Methodology To Improve The Understanding Of Dna Methylation Data, Lindsay Leigh Waite Jones

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The study of epigenetics involves the investigation of genomic elements that do not directly affect DNA sequence but are stable and preserved during cell division. One of the most commonly studied epigenetic elements is DNA methylation, which occurs when a methyl group is added to a cytosine residue in the DNA sequence. The advancement of technology to quantify DNA methylation, including bisulfite sequencing and bisulfite microarrays, has led to a large amount of available data. However, many questions still remain as to how to statistically analyze this data. This dissertation addresses some statistical concerns related to the analysis of DNA …

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Robust Production Of Mature Ribosomal Rna Is Directly Influenced By Multiple Steps Within The Transcription Cycle, Krysta Engel Jan 2015

Robust Production Of Mature Ribosomal Rna Is Directly Influenced By Multiple Steps Within The Transcription Cycle, Krysta Engel

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Cellular growth depends on the capacity for protein synthesis, and likewise ribosome biogenesis. Therefore, robust rRNA synthesis by RNA Polymerase I (Pol I) is a critical component of cell growth. The work reported in this dissertation highlights the contribution of polymerase domains and trans-acting proteins during rRNA synthesis and ribosome biogenesis. Eukaryotes utilize three homologous nuclear RNA polymerases (RNAPs) to express their genomes. The trigger loop (TL) is a well conserved region within the active site of multi-subunit RNAPs that plays a direct role during the nucleotide addition cycle. Analysis of Pol II TL mutants has suggested that catalysis is …

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Assessment Of Student-Created Videos As An Alternate Laboratory Assignment And Design And Implementation Of Classroom Activities Designed To Improve Student Retention And Learning, Mitzy Ann Erdmann Jan 2015

Assessment Of Student-Created Videos As An Alternate Laboratory Assignment And Design And Implementation Of Classroom Activities Designed To Improve Student Retention And Learning, Mitzy Ann Erdmann

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This dissertation presents three educationally based research projects and describes how they are related. The first portion of this manuscript describes the development of an alternate assessment for the general chemistry laboratory that harnessed both the availability of and interest in using smart phone technology in an educational setting. Student-created technique videos were implemented into the general chemistry laboratory curriculum in order to asynchronously monitor student use of standard laboratory equipment. A feasibility study was performed first, which showed that students were able to create videos that showed themselves performing standard laboratory techniques. Teaching assistants reported being able to easily …

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Metabolic And Oxidative Regulation Of Neuronal Autophagy And Survival, Matthew Dodson Jan 2015

Metabolic And Oxidative Regulation Of Neuronal Autophagy And Survival, Matthew Dodson

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Neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease and Huntington's disease are all characterized by metabolic dysfunction, increased oxidative damage to proteins and organelles, formation of proteinaceous inclusions, decreased autophagic and proteasomal function, and eventual neuronal and glial cell death. While our understanding of the mechanisms that underlie many of these pathologies is constantly growing, their exact cause, onset, interplay and progression still remain unclear. The gap between the description of disease pathologies and understanding the fundamental mechanisms of disease pathogenesis, progression and potential therapeutics to mitigate disease progression is still large. Based on the observation that altered glucose utilization, …

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The Characterization Of Human Cytosolic Sulfotransferase 1a1: Interactions With 17Α-Ethinylestradiol, Katie Jo Glowacki Jan 2015

The Characterization Of Human Cytosolic Sulfotransferase 1a1: Interactions With 17Α-Ethinylestradiol, Katie Jo Glowacki

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Human cytosolic sulfotransferases (SULTs) are a family of Phase II conjugating enzymes that facilitate the transfer of a sulfonate moiety from 3’phosphoadenosine 5’phosphosulfate (PAPS) to hydroxyl or amine groups of acceptor substrates. SULT1A1, located in many tissues throughout the human body including the liver, is important in the metabolism of many endogenous, exogenous, xenobiotic, and drug compounds. The majority of substrates for SULT1A1 are small neutral phenols including 1-naphthol and acetaminophen; however, SULT1A1 sulfates larger compounds including 17β-estradiol (E2) and raloxifene. SULT1A1 conjugates E2 with a Km of 2.3 µM and the structure of E2 is almost identical to the …

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Probing Astrocytes With Carbon Nanotubes And Assessing Their Effects On Astrocytic Structural And Functional Properties, Manoj K. Gottipati Jan 2015

Probing Astrocytes With Carbon Nanotubes And Assessing Their Effects On Astrocytic Structural And Functional Properties, Manoj K. Gottipati

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Single-walled carbon nanotubes, chemically-functionalized with polyethylene glycol (SWCNT-PEG) have been shown to modulate the morphology and proliferation characteristics of astrocytes in culture, when applied to the cells as colloidal solutes or as films upon which the cells can attach and grow. These changes were associated with a change in the immunoreactivity of the astrocyte-specific protein, glial fibrillary acidic protein (GFAP); the solutes and films caused an increase and a decrease in GFAP levels, respectively. To assess if these morpho-functional changes induced by the SWCNT-PEG modalities are dependent on GFAP or if the changes in GFAP levels are independent events, I …

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Emotion Regulation And Neuropathic Pain Following Spinal Cord Injury (Sci): Influence Of Emotional Processes On The Efficacy Of A Novel Treatment Paradigm For Sci-Related Pain, Juliette Galindo Jan 2015

Emotion Regulation And Neuropathic Pain Following Spinal Cord Injury (Sci): Influence Of Emotional Processes On The Efficacy Of A Novel Treatment Paradigm For Sci-Related Pain, Juliette Galindo

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While spinal cord injury (SCI) is a relatively rare in the general population, it has significant implications on functionality, independence, and quality of life for individuals who are affected by it. Common sequelae of SCI include sensorimotor dysfunction and pain symptoms that are often severe. More specifically, approximately 33% of individuals with SCI experience severe, intractable neuropathic pain. Additionally, treatments for neuropathic pain have variable efficacy and/or many side effects. While SCI-related neuropathic pain is thought to be related to cortical reorganization and nerve damage, there may be psychological factors that contribute to increased pain severity and variable treatment response. …

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Bioenergetics As A Biomarker Of Health And Disease, Philip Kramer Jan 2015

Bioenergetics As A Biomarker Of Health And Disease, Philip Kramer

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The increasing prevalence of metabolic syndrome, diabetes, atherosclerosis, and many other diseases only recently associated with aberrant metabolism, have led to a de-mand for clinical assays to determine a patient’s mitochondrial health. With the rapidly growing interest in personalized medicine, such an assay would ideally be able to capture the metabolic changes associated with oxidative stress, inflammation, and therapy of a patient in a swift and non-invasive manner. Short of tissue biopsies, this burgeoning field of Translational Bioenergetics has had minimal success in obtaining sufficient human cells and the means to assess them both accurately and swiftly. The purpose of …

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Defining The Role Of Trps1 In Phosphate Mediated Mineralization, Maria Kuzynski Jan 2015

Defining The Role Of Trps1 In Phosphate Mediated Mineralization, Maria Kuzynski

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Mineralization is a tightly controlled bi-phasic process that occurs when crystals of calcium and phosphate (Pi) are laid down within the extracellular matrix. However, the molecular networks regulating the initiation and progression of this process have not been well characterized. Pi, as one of the components of mineral crystals and a signaling molecule that regulates expression of mineralization-related genes, is essential to the mineralization process. In our studies, we discovered a novel function for Pi in this process: Pi is sufficient to induce secretion of matrix vesicles, which support the initiation of mineralization. Furthermore, we determined that this induction is …

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The Biological And Conservational Implications Of Hatchling Biology In The Kemp's Ridley (Lepidochelys Kempii) Sea Turtle, Amy Nicole Bonka Jan 2015

The Biological And Conservational Implications Of Hatchling Biology In The Kemp's Ridley (Lepidochelys Kempii) Sea Turtle, Amy Nicole Bonka

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The Kemp’s ridley sea turtle is currently listed as critically endangered, and has a very limited range, often found along the Atlantic coast though primarily inhabiting the Gulf of Mexico, with the majority of all nesting occurring near Rancho Nuevo, Mexico. Historically, large numbers of turtles have been reported to nest at Rancho Nuevo; though numbers dropped due to egg take and by-catch in the fishing and shrimping industries. Extensive conservation efforts over the last several decades significantly increased the number of nests; however the recovery status of the Kemp’s ridley is still in question, and the continued research and …

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Preliminary Characterization Of The Microbial Community In The Bonneville Salt Flats, Garner Lansing Boogaerts Jan 2015

Preliminary Characterization Of The Microbial Community In The Bonneville Salt Flats, Garner Lansing Boogaerts

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Hypersaline environments (salt concentrations greater than two molar) are found on all continents and represent a woefully understudied ecosystem. To date, most of the hypersaline environments studied have been either lakes (e.g. The Great Salt Lake, Utah) or deep ocean/sea brine pools (e.g. Red Sea), both of which have an abundance of accessible water for the organisms living there. However, more extreme hypersaline environments have not been characterized as thoroughly. One of these environments is the Bonneville Salt Flats (BSF) in Western Utah. The BSF is 80 square miles in size and consists of a salt crust of varying thickness …

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Transferring Virtual Reality Training To Real World Settings In Individuals With Low Vision And Dual-Sensory Impairments, Ellen Lambert Bowman Jan 2015

Transferring Virtual Reality Training To Real World Settings In Individuals With Low Vision And Dual-Sensory Impairments, Ellen Lambert Bowman

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TRANSFERRING VIRTUAL REALITY TRAINING TO REAL WORLD SETTINGS IN INDIVIDUALS WITH LOW VISION AND DUAL-SENSORY IMPAIRMENTS ELLEN LAMBERT BOWMAN VISION SCIENCE GRADUATE PROGRAM ABSTRACT The goal of this study was to determine if individuals with low vision could learn useful visual skills in Virtual Reality and could transfer these skills to the real world. To achieve this goal, one set of Orientation & Mobility (O&M) skills, using the near lane parallel traffic surge to decide the safest timing to cross a signal controlled street, was selected. Twelve participants with vision too poor to use pedestrian signals were randomly assigned to …

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Predictive Modeling Of Ocular Surface Disease States Using Multiple Inflammatory Biomarkers, John L. Bradley Jan 2015

Predictive Modeling Of Ocular Surface Disease States Using Multiple Inflammatory Biomarkers, John L. Bradley

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ABSTRACT Purpose The aim of this study was to adapt conjunctival impression cytology (CIC) and RNA isolation and processing procedures for gene expression analysis of ocular surface inflammatory biomarkers. The RNA yield and quality should be sufficient to enable quantitative real-time PCR of no less than 12 key target genes, with the goal of differentiating among dry eye groups. This study used the optimized inflammatory biomarker gene expression assay in a patient study to identify differences between dry eye and control participants. Materials and Methods CIC was used to collect conjunctival surface cells from 53 qualifying dry eye and control …

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Transient-State Kinetic Analysis Of The Rna Polymerase I Nucleotide Incorporation Mechanism, Francis Dean Appling Jan 2015

Transient-State Kinetic Analysis Of The Rna Polymerase I Nucleotide Incorporation Mechanism, Francis Dean Appling

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The diversity of enzymes and the reactions which they catalyze is enormous. Careful study of enzymatic reaction mechanisms has taught us a great deal about chemical reactivity and has given us insight into the chemical and physical basis of life. One particularly ubiquitous class of enzymes, the RNA polymerases, are expressed in all forms of life. RNA polymerases are central components of nucleic acid metabolism and display a variety of distinctive enzymatic features; two points which solicit their thorough study. The central theme of this dissertation is the use of kinetic techniques to describe enzymatic reaction mechanisms. Although the main …

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Assessment Of Streams And Aquatic Organisms In The Vicinity Of Birmingham, Alabama For The Presence And Biological Activity Of Endocrine-Disrupting Chemicals, Bryan Stuart Arwood Jan 2015

Assessment Of Streams And Aquatic Organisms In The Vicinity Of Birmingham, Alabama For The Presence And Biological Activity Of Endocrine-Disrupting Chemicals, Bryan Stuart Arwood

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Freshwater ecosystems play a central role in the environment. Through various processes such as nutrient recycling, groundwater recharging, and the attenuation of many pollutants these biological systems help to maintain environmental health. Unfortunately, many recent studies have identified emerging threats to these special environments and the life they sustain. One source of mounting concern is a group of compounds that interact with the endocrine systems of humans and wildlife. Known as endocrine disrupting chemicals (EDCs), these natural and synthetic chemicals may mimic or interfere with the action of natural hormones—thus disrupting the endocrine system. Multiple studies have reported negative effects …

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Transcriptional Regulation Of The Human Ribosomal Rna Gene, Blake L. Atwood Jan 2015

Transcriptional Regulation Of The Human Ribosomal Rna Gene, Blake L. Atwood

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The ribosome has the major role of synthesizing almost all the proteins of the cell. One of the main structural components of the ribosome are the ribosomal RNAs 18S, 28S, 5.8S and the 5S which are bound by numerous proteins to make up a fully functional unit. In the human genome there are approximately 400 copies of the rRNA gene, which contains all but the 5S rRNA in one long transcription unit. This gene is found in tandem repeats on the acrocentric arm of chromosomes 13, 14, 15, 21 and 22. It is critical that this gene is tightly regulated …

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The I507-Atc→Att Silent Codon Change Contributes To The Misfolding Of ∆F508 Cftr, Vedrana Bali Jan 2015

The I507-Atc→Att Silent Codon Change Contributes To The Misfolding Of ∆F508 Cftr, Vedrana Bali

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Synonymous codon changes (SCCs) do not alter the amino acid sequence of proteins, but may significantly change the phenotype. The frequency of synonymous codons is species- and gene-specific, described as codon usage bias (CUB). Over the past 50 years, research has shown that SCCs affect protein biogenesis, development of human disorders and the function of recombinant proteins developed for therapeutic applications. However, the molecular mechanisms by which SCCs alter the function of gene products are not completely understood. In Chapter 2 we summarize present knowledge in this field. The most common cause of cystic fibrosis (CF) is the deletion of …

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In- Vitro Wear Of Four Cad-Cam Materials In The Uab Wear Simulating Device, Ritika Bansal Jan 2015

In- Vitro Wear Of Four Cad-Cam Materials In The Uab Wear Simulating Device, Ritika Bansal

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In- vitro Wear of Four CAD- CAM Materials in the UAB Wear Simulating Device RITIKA BANSAL MS IN CLINICAL DENTISTRY ABSTRACT Hybrid ceramic/polymer blocks represent a new category of CAD/CAM materials that do not require heat treatment following milled fabrication and limited clinically relevant mechanical properties of these materials are available. Purpose: This study measures the hardness, flexural strength, modulus, and wear of 3 ceramic/polymer hybrid materials (LAVA Ultimate, Enamic, and Cerasmart), 2 reference glass ceramics (IPS e.max and Celtra Duo), and 1 reference composite material (Paradigm MZ100). Methods: Flexural strength specimens (n=10) (2.5 × 2.5 × 16 mm) were …

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Innovative Dart™ Ms Applications For Rapid Opioid Detection In Ante- And Post-Mortem Specimens, Rachel Crocker Beck Jan 2015

Innovative Dart™ Ms Applications For Rapid Opioid Detection In Ante- And Post-Mortem Specimens, Rachel Crocker Beck

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The studies presented herein were born through the observations of the challenges that are faced by forensic toxicology laboratories. While these challenges were first observed in the forensic toxicology field, they are common across clinical, workplace drug testing, and pain management laboratories alike. The challenge is how to increase efficiency without sacrificing quality. Current drug screening protocols such as immunoassays (IA), gas chromatography mass spectrometry (GC/MS), and liquid-liquid chromatography tandem mass spectrometry (LC/MS/MS) are robust but inefficient and limited, with some analyses providing only class information. These analyses when coupled require up to four days to complete for a confirmed, …

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Modulation Of The Unfolded Protein Response To Delay Apoptosis In An Autosomal Dominant Retinitis Pigmentosa Animal Model, Yogesh Bhootada Jan 2015

Modulation Of The Unfolded Protein Response To Delay Apoptosis In An Autosomal Dominant Retinitis Pigmentosa Animal Model, Yogesh Bhootada

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Retinitis pigmentosa (RP) is a group of retinal degenerative diseases characterized by the loss of rod photoreceptor cells that can be followed by cone degeneration eventually culminating in total photoreceptor cell loss. This disease affects approximately 1.5 million people worldwide and can be transmitted in an autosomal dominant (ADRP) manner accounting for nearly 30% of all RP cases. Dominant rhodopsin mutations have been divided into class I and class II based on the folding of rhodopsin protein, thermal stability, and chromophore regeneration. A threonine-17-methionine (T17M) mutation in rhodopsin is a class II mutation, characterized by a thermal instability/folding defect and …

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The Effect Of Bone-Implant Contact And Elastic Modulus In The Biomechanical Stability Of Temporary Anchorage Devices, Ghada Nimeri Jan 2015

The Effect Of Bone-Implant Contact And Elastic Modulus In The Biomechanical Stability Of Temporary Anchorage Devices, Ghada Nimeri

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ABSTRACT The purpose of this study was to analyze the microstrains of compact and trabecular bone caused by loading of different miniscrews at different healing times, and to compare these results to the limits of bone stability maintenance based on the Frost Mechanostat Theory. Materials and Methods: Theoretical calculations of microstrains of bone surrounding 10 different miniscrews were done. These miniscrews were considered under loading forces of 500 gm., and the microstains of both trabecular and compact bone were calculated separately when the thickness of the compact bone was at 1mm or 2mm. The microstrains were calculated at 4 different …

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Presence And Mobilization Of Staphylococcus Aureus Pathogenicity Islands (Sapis) Among Bovine Mastitis Isolates, Laura Kate Parker Jan 2015

Presence And Mobilization Of Staphylococcus Aureus Pathogenicity Islands (Sapis) Among Bovine Mastitis Isolates, Laura Kate Parker

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Bovine mastitis is inflammation of the mammary gland that occurs in cattle, as a result of invading bacteria. Staphylococcus aureus, a causative agent of bovine mastitis, produces toxins such as the toxic shock syndrome toxin (TSST-1) and the staphylococcal enterotoxins (SEs). The genes for these toxins are coded on S. aureus pathogenicity islands (SaPIs), which are mobile genetic elements associated with virulence factors. SaPIs can be mobilized by bacteriophages, resulting in the production of transducing particles that can spread virulence factors throughout a bacterial population. This research assessed the role and prevalence of SaPIs among bovine mastitis samples. In this …

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Gsk3 Regulation Of Suprachiasmatic Neuronal Excitability And Light Entrainment, Jodi Paul Jan 2015

Gsk3 Regulation Of Suprachiasmatic Neuronal Excitability And Light Entrainment, Jodi Paul

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Circadian rhythms are approximately 24-hour cycles in behavioral and physiological processes, such as sleep/wake cycles and cognition. In mammals, these rhythms are endogenously generated and entrained to the external light cycle by the primary circadian pacemaker, the suprachiasmatic nucleus (SCN). A hallmark characteristic of SCN neurons is the daily rhythm in the spontaneous action potential frequency, with high activity during the day and low activity at night. These SCN firing rate patterns are critical for maintaining robust, consolidated behavioral rhythms, and persistent changes in SCN neuronal activity are involved light-induced behavioral shifts. Many of the ionic components underlying daily and …

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The Mspa Nanopore As A Sensor For Dna Sequencing, Mikhail Pavlenok Jan 2015

The Mspa Nanopore As A Sensor For Dna Sequencing, Mikhail Pavlenok

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Nanopore sequencing is a novel and promising DNA sequencing method. This single molecule technique is capable of long reads, retains epigenetic information, and is inexpensive and fast. In this method ionic current is measured while single-stranded DNA is electrophoretically translocated through a nanometer-scale pore. Each passing nucleotide blocks current with characteristic amplitude and duration which are used to identify DNA sequence. MspA is the primary porin of M. smegmatis and mediates the diffusion of small, hydrophilic nutrients across the outer membrane. MspA is an octameric, channel-forming protein and represents the founding member of a new class of mycobacterial outer membrane …

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Exploiting Novel Interactions With Parp1 In Dna Repair Proficient Human Breast Cancers, Jennifer Anne Stanley Jan 2015

Exploiting Novel Interactions With Parp1 In Dna Repair Proficient Human Breast Cancers, Jennifer Anne Stanley

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Breast cancer remains the most frequently diagnosed cancer amongst women worldwide. Despite advances in treatment, patients with more aggressive basal-like and HER2-positive cancer experience high rates of recurrence and necessitate novel therapeutic approaches. A class of inhibitors targeted against poly (ADP-ribose) polymerases (PARP), important DNA repair proteins, are effective in cancers with a defective DNA repair response. As such, extensive preclinical and clinical research has examined their efficacy in these cancers. Although this data is promising, it is only applicable to a lim-ited patient population. The main goal of this dissertation is to expand the utility of these well-tolerated drugs …

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