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Full-Text Articles in Molecular Biology

Investigating The Roles Of Fucosylation And Calcium Signaling In Melanoma Invasion, Tyler S. Keeley Nov 2018

Investigating The Roles Of Fucosylation And Calcium Signaling In Melanoma Invasion, Tyler S. Keeley

Graduate Theses and Dissertations

Melanoma is the deadliest form of skin cancer. Prognosis for early stage melanoma patients is excellent, and surgery is often curative for these patients. However, once patients have presented with invasive disease, the average 5-year survival rate drops significantly from over 90% to between 10 and 15%. Several therapies have been developed to target a commonly mutated oncogene BRAF, or its downstream effectors. Unfortunately, while these treatments show robust initial response, most patients relapse within a year. Moreover, therapy-resistant tumors are often more invasive and metastatic. Therefore, it is important to investigate the molecular mechanisms underlying melanoma invasion and metastasis ...


Investigating The Role Of The Rna Binding Protein Lin28 In The Human Placenta: Implications For Preeclampsia, John Canfield Nov 2018

Investigating The Role Of The Rna Binding Protein Lin28 In The Human Placenta: Implications For Preeclampsia, John Canfield

Graduate Theses and Dissertations

An essential event during early pregnancy is the invasion of trophoblasts into the maternal decidua, which is necessary for proper implantation and establishment of maternal-fetal interface and ultimately allows for proper nutrient exchange and immunological tolerance of the growing fetus. For this invasion to occur, cells originating from the trophectoderm undergo an epithelial to mesenchymal transition to become invasive extravillous trophoblasts and begin invading the uterine decidual tissue. Through the secretion of matrix metalloproteinases and through interactions with many cytokines and cell-adhesion molecules, this well-orchestrated process of trophoblast invasion results in extensive remodeling of the maternal spiral vasculature by the ...


Investigation Of Alcohol-Induced Changes In Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics, Crystina Leah Kriss Apr 2018

Investigation Of Alcohol-Induced Changes In Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics, Crystina Leah Kriss

Graduate Theses and Dissertations

Alcohol liver disease (ALD) is a major health concern throughout the world. Currently, in the United States, 17 million people suffer from alcoholism, of which 1.4 million people are receiving treatment [1, 2]. The link between ethanol metabolism, reactive oxygen species (ROS) and liver injury in ALD has been well characterized over the last couple decades [3-10]. Ethanol metabolism relies on the availability of the cofactor NAD+ for the oxidation of ethanol into acetate, consequently causing alterations in redox potential. Redox dysfunction within the mitochondria can affect multiple pathways important in maintaining cellular homeostasis. Chapter 1 provides an introduction ...


The Role Of Phosphohistidine Phosphatase 1 In Ethanol-Induced Liver Injury, Daniel Richard Martin Apr 2018

The Role Of Phosphohistidine Phosphatase 1 In Ethanol-Induced Liver Injury, Daniel Richard Martin

Graduate Theses and Dissertations

Chronic liver diseases, which includes alcoholic liver disease (ALD), are consistently among the top 15 leading causes of death in the United States. ALD is characterized by progression from a normal liver to fatty liver disease (hepatic steatosis), which can lead to cirrhosis, alcoholic hepatitis, and liver failure. We have identified a novel role of phosphohistidine signaling, mediated through phosphohistidine phosphatase 1 (PHPT1), in the onset of hepatic steatosis. We have identified PHPT1 as a target of selective oxidation following acute ethanol exposure as well as being downregulated following chronic ethanol exposure. We mapped the oxidative modification site and developed ...


Role Of Heat Shock Transcription Factor 1 In Ovarian Cancer Epithelial-Mesenchymal Transition And Drug Sensitivity, Chase David Powell Nov 2017

Role Of Heat Shock Transcription Factor 1 In Ovarian Cancer Epithelial-Mesenchymal Transition And Drug Sensitivity, Chase David Powell

Graduate Theses and Dissertations

The heat shock response (HSR) is a robust cellular reaction to mitigate protein damage from heat and other challenges to the proteome. This protective molecular program in humans is controlled by heat shock transcription factor 1 (HSF1). Activation of HSF1 leads to the induction of an array of cytoprotective genes, many of which code for chaperones. These chaperones, known as heat shock proteins (HSPs), are responsible for maintaining the functional integrity of the proteome. HSPs achieve this by promoting proper folding and assembly of nascent proteins, refolding denatured proteins, and processing for degradation proteins and aggregates which cannot be returned ...


The Role Of Sgs1 And Exo1 In The Maintenance Of Genome Stability., Lillian Campos-Doerfler Nov 2017

The Role Of Sgs1 And Exo1 In The Maintenance Of Genome Stability., Lillian Campos-Doerfler

Graduate Theses and Dissertations

Genome instability is a hallmark of human cancers. Patients with Bloom’s syndrome, a rare chromosome breakage syndrome caused by inactivation of the RecQ helicase BLM, result in phenotypes associated with accelerated aging and develop cancer at a very young age. Patients with Bloom’s syndrome exhibit hyper-recombination, but the role of BLM and increased genomic instability is not fully characterized. Sgs1, the only member of the RecQ family of DNA helicases in Saccharomyces cerevisiae, is known to act both in early and late stages of homology-dependent repair of DNA damage. Exo1, a 5′–3′ exonuclease, first discovered to play ...


Mechanism Elucidation And Inhibitor Discovery Against Serine And Metallo-Beta-Lactamases Involved In Bacterial Antibiotic Resistance, Orville A. Pemberton Nov 2017

Mechanism Elucidation And Inhibitor Discovery Against Serine And Metallo-Beta-Lactamases Involved In Bacterial Antibiotic Resistance, Orville A. Pemberton

Graduate Theses and Dissertations

The emergence and proliferation of Gram-negative bacteria expressing β-lactamases is a significant threat to human health. β-Lactamases are enzymes that degrade the β-lactam antibiotics (e.g., penicillins, cephalosporins, monobactams, and carbapenems) that we use to treat a diverse range of bacterial infections. Specifically, β-lactamases catalyze a hydrolysis reaction where the β-lactam ring common to all β-lactam antibiotics and responsible for their antibacterial activity, is opened, leaving an inactive drug. There are two groups of β-lactamases: serine enzymes that use an active site serine residue for β-lactam hydrolysis and metalloenzymes that use either one or two zinc ions for catalysis. Serine ...


Cell Division Regulation In Staphylococcus Aureus, Catherine M. Spanoudis Oct 2017

Cell Division Regulation In Staphylococcus Aureus, Catherine M. Spanoudis

Graduate Theses and Dissertations

Cell division is a fundamental biological process that occurs in all kingdoms of life. Our understanding of cell division in bacteria stems from studies in the rod-shaped model organisms: Gram-negative Escherichia coli and Gram-positive Bacillus subtilis. The molecular underpinnings of cell division regulation in non-rod-shaped bacteria remain to be studied in detail. Rod-shaped bacteria possess many positive and negative regulatory proteins that are essential to the proper placement of the division septa and ultimately the production of two identical daughter cells, many of which are absent in cocci. Given that essential cell division proteins are attractive antibacterial drug targets, it ...


Microfluidic Biopsy Trapping Device For The Real-Time Monitoring Of The Tumor Microenvironment, Angela Holton Oct 2017

Microfluidic Biopsy Trapping Device For The Real-Time Monitoring Of The Tumor Microenvironment, Angela Holton

Graduate Theses and Dissertations

The tumor microenvironment is composed of cellular and stromal components such as tumor cells, mesenchymal cells, immune cells, cancer associated fibroblasts and the supporting extracellular matrix. The tumor microenvironment provides crucial support for growth and progression of tumor cells and affects tumor response to therapeutic interventions. To better understand tumor biology and to develop effective cancer therapeutic agents it is important to develop preclinical platforms that can faithfully recapitulate the tumor microenvironment and the complex interaction between the tumor and its surrounding stromal elements. Drug studies performed in vitro with conventional two-dimensional cancer cell line models do not optimally represent ...


Modeling Of Dynamic Allostery In Proteins Enabled By Machine Learning, Mohsen Botlani-Esfahani Jul 2017

Modeling Of Dynamic Allostery In Proteins Enabled By Machine Learning, Mohsen Botlani-Esfahani

Graduate Theses and Dissertations

Regulation of protein activity is essential for normal cell functionality. Many proteins are regulated allosterically, that is, with spatial gaps between stimulation and active sites. Biological stimuli that regulate proteins allosterically include, for example, ions and small molecules, post-translational modifications, and intensive state-variables like temperature and pH. These effectors can not only switch activities on-and-off, but also fine-tune activities. Understanding the underpinnings of allostery, that is, how signals are propagated between distant sites, and how transmitted signals manifest themselves into regulation of protein activity, has been one of the central foci of biology for over 50 years. Today, the importance ...


Discovering Antibacterial And Anti-Resistance Agents Targeting Multi-Drug Resistant Eskape Pathogens, Renee Fleeman Jul 2017

Discovering Antibacterial And Anti-Resistance Agents Targeting Multi-Drug Resistant Eskape Pathogens, Renee Fleeman

Graduate Theses and Dissertations

Antibiotic resistance has been a developing problem for mankind in recent decades and multi-drug resistant bacteria are now encountered that are resistant to all treatment options available. In 2014, the World Health Organization announced that this problem is driving us towards a “post-antibiotic era” that will change the face of modern medicine as we know it. If lack of novel antibiotic development and FDA approval continues, by the year 2050, 10 million people will die each year to an antimicrobial resistant bacterial infection. With lack of pharmaceutical industry involvement in developing novel antibiotics, the responsibility now lies within the academic ...


Functional Roles Of Matrix Metalloproteinases In Bone Metastatic Prostate Cancer, Jeremy S. Frieling May 2017

Functional Roles Of Matrix Metalloproteinases In Bone Metastatic Prostate Cancer, Jeremy S. Frieling

Graduate Theses and Dissertations

Skeletal metastasis is a lethal component of many advanced cancers including prostate, the second most common cancer among men. Patients whose prostate cancer is localized and detected early benefit from multiple treatment options ranging from active surveillance to radiation and surgery, resulting in a 5-year survival rate of nearly 100%. Unfortunately, the prognosis and survival for patients with advanced metastatic disease is much worse due to the highly aggressive nature of the disease and a paucity of treatment options. Understanding the mechanisms and interactions that occur between metastatic cancer cells and the bone will enable the future treatment landscape for ...


Therapeutic Modulation Of Cancer Metabolism With Dichloroacetate And Metformin, Nathan Patrick Ward Apr 2017

Therapeutic Modulation Of Cancer Metabolism With Dichloroacetate And Metformin, Nathan Patrick Ward

Graduate Theses and Dissertations

The robust glycolytic metabolism of glioblastoma multiforme (GBM) has proven them susceptible to increases in oxidative metabolism induced by the pyruvate mimetic dichloroacetate (DCA). Recent reports demonstrate that the anti-diabetic drug metformin enhances the damaging oxidative stress associated with DCA treatment in cancer cells. We sought to elucidate the role of metformin’s reported activity as a mitochondrial complex I inhibitor in the enhancement of DCA cytotoxicity in the VM-M3 model of GBM. We demonstrated that metformin potentiated DCA-induced superoxide production and that this was required for enhanced cytotoxicity towards VM-M3 cells with the combination. Similarly, rotenone enhanced oxidative stress ...


Uncovering Transcriptional Activators And Targets Of Hsf-1 In Caenorhabditis Elegans, Jessica Brunquell Apr 2017

Uncovering Transcriptional Activators And Targets Of Hsf-1 In Caenorhabditis Elegans, Jessica Brunquell

Graduate Theses and Dissertations

In order to survive, cells must be able to cope with a variety of environmental stressors. The heat shock response (HSR) is a pro-survival mechanism employed by cells in response to protein denaturing stress, such as heat. Since its discovery in 1960, the heat shock response has been found to be regulated by the transcription factor heat shock factor 1 (HSF1). During periods of increased stress, HSF1 undergoes a multi-step process of activation that involves homotrimerization, DNA-binding, and post-translational regulatory modifications, all of which ultimately function to control the transcription of chaperone genes. These chaperone genes encode molecular chaperone proteins ...


Mass-Spectrometry Based Proteomics Of Age-Related Changes In Murine Microglia, Antwoine Flowers Mar 2017

Mass-Spectrometry Based Proteomics Of Age-Related Changes In Murine Microglia, Antwoine Flowers

Graduate Theses and Dissertations

The last century has seen a steady increase in the extension of the average lifespan. This has concomitantly produced higher incidences of age-related chronic degenerative diseases like Alzheimer’s and Parkinson’s diseases. Age is the single greatest risk factor for the development of not just these degenerative conditions but cancer as well. The aged niche undergoes a number of maladaptive changes that allow underlying conditions to present and progress. Exactly which changes, contribute to the progression of which disease is currently an area of intense study. However, these answers often present therapeutic targets for disease prevention. Age is characterized ...


Development Of Tools For Stable Transfection In The Human Filarial Parasite Brugia Malayi Via The Piggybac Transposon System, Johan Chabanon Mar 2017

Development Of Tools For Stable Transfection In The Human Filarial Parasite Brugia Malayi Via The Piggybac Transposon System, Johan Chabanon

Graduate Theses and Dissertations

Brugia malayi is one of three species of nematode known to cause lymphatic filariasis (LF) in humans. LF infects over 120 million people, causing debilitating disease. Various global programs have been launched in the past 20 years to eliminate LF. These programs have greatly scaled up the resources and efforts allocated to halting the transmission and reducing disease burden. Only a few drugs are used to treat LF, and resistance is thus a devastating possibility. Research aimed at identifying new drug targets could therefore prove essential in elimination of LF.

Genetic manipulation of B. malayi has been limited to transient ...


A Novel Abi-Domain Protein Controls Virulence Determinant Production In Staphylococcus Aureus, Stephanie Michelle Marroquin Mar 2017

A Novel Abi-Domain Protein Controls Virulence Determinant Production In Staphylococcus Aureus, Stephanie Michelle Marroquin

Graduate Theses and Dissertations

A major factor in the success of Staphylococcus aureus as a pathogen is its vast arsenal of virulence determinants and, more importantly, the tight and precisely- timed regulation of these factors. Here we investigate the product of the S. aureus gene, SAUSA300_1984, encoding a putative transmembrane protein. This as yet uncharacterized protein belongs to the Abi (abortive infection) family, which are commonly annotated as CAAX-proteases, and are significantly understudied in prokaryotes. In S. aureus the disruption of SAUSA300_1984 results in a drastic reduction of proteolytic and hemolytic activity, as well as diminished pigmentation. This phenotype appears to be mediated through ...


Changing The Pathobiological Paradigm In Myelodysplastic Syndromes: The Nlrp3 Inflammasome Drives The Mds Phenotype, Ashley Basiorka Jan 2017

Changing The Pathobiological Paradigm In Myelodysplastic Syndromes: The Nlrp3 Inflammasome Drives The Mds Phenotype, Ashley Basiorka

Graduate Theses and Dissertations

Note: Portions of this abstract have been previously published in the journal Blood, Basiorka et al. Blood. 2016 Oct 13, and has been reproduced in this manuscript with permission from the publisher.

Myelodysplastic syndromes (MDS) are genetically diverse hematopoietic stem cell malignancies that share a common phenotype of cytological dysplasia, ineffective hematopoiesis and aberrant myeloid lineage maturation. Apoptotic cell death potentiated by inflammatory cytokines has been considered a fundamental feature of MDS for over two decades. However, this non-inflammatory form of cell death cannot account for the inflammatory nature of these disorders. We report that a hallmark of lower-risk (LR ...


The Effects Of Phytohormones And Isoprenoids In Dihydroartemisinin-Induced Dormancy In The Erythrocytic Stages Of Plasmodium Falciparum, Marvin Duvalsaint Duvalsaint Nov 2016

The Effects Of Phytohormones And Isoprenoids In Dihydroartemisinin-Induced Dormancy In The Erythrocytic Stages Of Plasmodium Falciparum, Marvin Duvalsaint Duvalsaint

Graduate Theses and Dissertations

Our ability to control malaria has been challenged by increasing antimalarial resistance. Plasmodium falciparum undergoes dormancy in the blood stages which is hypothesized to be a means by which they are able to survive under drug pressure. This helps select for resistant parasites which grow following removal of drug. The mechanisms behind dormancy and the subsequent recrudescence are not fully understood but translating knowledge from related organisms which undergo a similar phenomenon might shed some light. Higher plants utilize dormancy during the early development stages to survive under unfavorable conditions, increasing fitness of the seedling and ensuring viability when this ...


Mitochondrial Heteroplasmy Contributes To The Dynamic Atovaquone Resistance Response In Plasmodium Falciparum, Sasha Victoria Siegel Nov 2016

Mitochondrial Heteroplasmy Contributes To The Dynamic Atovaquone Resistance Response In Plasmodium Falciparum, Sasha Victoria Siegel

Graduate Theses and Dissertations

Of the considerable challenges researchers face in the control and elimination of malaria, the development of antimalarial drug resistance in parasite populations remains a significant hurdle to progress worldwide. Atovaquone is used in combination with proguanil (Malarone) as an antimalarial treatment in uncomplicated malaria, but is rendered ineffective by the rapid development of atovaquone resistance during treatment. Previous studies have established that de novo mutant parasites confer resistance to atovaquone with a substitution in amino acid 268 in the cytochrome b gene encoded by the parasite mitochondrial genome, yet much is still unknown about how this resistance develops, and whether ...


Gene Expression Profiling And The Role Of Hsf1 In Ovarian Cancer In 3d Spheroid Models, Trillitye Paullin Nov 2016

Gene Expression Profiling And The Role Of Hsf1 In Ovarian Cancer In 3d Spheroid Models, Trillitye Paullin

Graduate Theses and Dissertations

Ovarian cancer is the most lethal gynecological cancer, with over 200,000 women diagnosed each year and over half of those cases leading to death. These poor statistics are related to a lack of early symptoms and inadequate screening techniques. This results in the cancer going undetected until later stages when the tumor has metastasized through a process that requires the epithelial to mesenchymal transition (EMT). In lieu of traditional monolayer cell culture, EMT and cancer progression in general is best characterized through the use of 3D spheroid models. In this study, we examine gene expression changes through microarray analysis ...


Significance Of Pten Phosphorylation And Its Nuclear Function In Lung Cancer, Prerna Malaney Nov 2016

Significance Of Pten Phosphorylation And Its Nuclear Function In Lung Cancer, Prerna Malaney

Graduate Theses and Dissertations

Phosphorylation mediated inactivation of PTEN leads to multiple malignancies with increased severity. However, the consequence of such inactivation on downstream functions of PTEN are poorly understood. Therefore, the objective of my thesis is to ascertain the molecular mechanisms by which PTEN phosphorylation drives lung cancer. PTEN phosphorylation at the C-terminal serine/threonine cluster abrogates its tumor suppressor function. Despite the critical role of the PTEN C-tail in regulating its function, the crystal structure of the C-tail remains unknown. Using bioinformatics and structural analysis, I determined that the PTEN C-tail is an intrinsically disordered region and is a hot spot for ...


Contribution Of Epithelial Hypoxia Signaling To Pulmonary Fibrosis: Role Of Fak1 And Galectin-1 As Driver Molecules, Jaymin J. Kathiriya Oct 2016

Contribution Of Epithelial Hypoxia Signaling To Pulmonary Fibrosis: Role Of Fak1 And Galectin-1 As Driver Molecules, Jaymin J. Kathiriya

Graduate Theses and Dissertations

Idiopathic Pulmonary Fibrosis (IPF) is a deadly disease of unknown origin, which causes 80,000 deaths every year in the US and Europe combined. Unknown etiology and late diagnosis, combined with limited treatment options, contribute to a dismal survival rate of 3-5 years post diagnosis. Although molecular mechanisms underlying IPF pathogenesis and progression have been studied for over two decades, lack of in vivo models that recapitulate chronic, progressive, and irreversible nature of IPF have contributed to limited therapeutic success in clinical trials. Currently, only two drugs, Pirfenidone and Nintedanib, are approved for IPF treatment in the US, with their ...


Cardiovascular Regulation By Kvβ1.1 Subunit, Jared Tur Oct 2016

Cardiovascular Regulation By Kvβ1.1 Subunit, Jared Tur

Graduate Theses and Dissertations

Heterologous expression systems such as COS-7 cells have demonstrated the profound effects of KCNAB1-3 or Kvβ1-3 proteins on voltage gated potassium channels (Kv) channels. Indeed, in the presence of these β-subunits transiently expressed Kv channels are often modulated in multiple ways. Kv channel membrane expression is often increased in the presence of β-subunits. In addition, non-inactivating Kv currents suddenly become fast-inactivating and fast-inactivating channels become even faster. While much research has demonstrated the profound effects the β-subunits in particular the Kvβ1 subunit have on transiently expressed Kv currents little to date is known of the physiological role it may play ...


Regulation Of Nachrs And Stemness By Nicotine And E-Cigarettes In Nsclc, Courtney Schaal Aug 2016

Regulation Of Nachrs And Stemness By Nicotine And E-Cigarettes In Nsclc, Courtney Schaal

Graduate Theses and Dissertations

Lung cancer is the leading cause of cancer-related death in both men and women, nationally and internationally and kills more people each year than breast, prostate, and colon cancers combined. Non-small cell lung carcinoma (NSCLC) is the most common histological subtype of lung cancer, and accounts for 85% of all cases. Cigarette smoking is the single greatest risk factor for lung cancer, and is correlated with 80-90% of all lung cancer deaths. Nicotine, the addictive component of tobacco smoke, is not a carcinogen and cannot initiate tumors itself; however, it is known to act as a tumor promoter, by enhancing ...


Computational Modeling Of Allosteric Stimulation Of Nipah Virus Host Binding Protein, Priyanka Dutta Jul 2016

Computational Modeling Of Allosteric Stimulation Of Nipah Virus Host Binding Protein, Priyanka Dutta

Graduate Theses and Dissertations

Nipah belongs to the family of paramyxoviruses that cause numerous fatal diseases in humans and farm animals. There are no FDA approved drugs for Nipah or any of the paramyxoviruses. Designing antiviral therapies that are more resistant to viral mutations require understanding of molecular details underlying infection. This dissertation focuses on obtaining molecular insights into the very first step of infection by Nipah. Such details, in fact, remain unknown for all paramyxoviruses. Infection begins with the allosteric stimulation of Nipah virus host binding protein by host cell receptors. Understanding molecular details of this stimulation process have been challenging mainly because ...


A Caenorhabditis Elegans Model To Detect Developmental Teratogens With Adverse Reproductive And Metabolic Effects, Alexis Ann Killeen Jul 2016

A Caenorhabditis Elegans Model To Detect Developmental Teratogens With Adverse Reproductive And Metabolic Effects, Alexis Ann Killeen

Graduate Theses and Dissertations

Obesity is a current epidemic in the United States. Greater than one third of adults and nearly one fifth of children are classified as obese (Ogden, 2014). Increased awareness of this problem has triggered interest into the potentially causal agents in our environment. These agents, termed obesogens, are a type of teratogen hypothesized to work during embryonic development by programming offspring to store excess fat. A type of teratogen, obesogens are also typically reprotoxic, affecting germline development and embryonic viability. These noxious teratogens span a variety of different chemical classes including estrogen mimics, metals and metalloids, biocides, and even voluntary ...


Cell Cycle Arrest By Tgfß1 Is Dependent On The Inhibition Of Cmg Helicase Assembly And Activation, Brook Samuel Nepon-Sixt Jun 2016

Cell Cycle Arrest By Tgfß1 Is Dependent On The Inhibition Of Cmg Helicase Assembly And Activation, Brook Samuel Nepon-Sixt

Graduate Theses and Dissertations

Tumorigenesis is a multifaceted set of events consisting of the deregulation of several cell-autonomous and tissue microenvironmental processes that ultimately leads to the acquisition of malignant disease. Transforming growth factor beta (TGFß) and its family members are regulatory cytokines that function to ensure proper organismal development and the maintenance of homeostasis by controlling cellular differentiation, proliferation, adhesion, and survival, as well as by modulating components of the cellular microenvironment and immune system. The pleiotropic control by TGFß of these cell intrinsic and extrinsic factors is intimately linked to the prevention of tumor formation, the specifics of which are dependent on ...


Intrinsic Disorder Where You Least Expect It: The Incidence And Functional Relevance Of Intrinsic Disorder In Enzymes And The Protein Data Bank, Shelly Deforte Jun 2016

Intrinsic Disorder Where You Least Expect It: The Incidence And Functional Relevance Of Intrinsic Disorder In Enzymes And The Protein Data Bank, Shelly Deforte

Graduate Theses and Dissertations

Intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs) exist as interconverting conformational ensembles, without a single fixed three-dimensional structure in vivo. The focus in the literature up to this point has been primarily on IDPs that are mostly or entirely disordered. Therefore, we have an incomplete understanding of the incidence and functional relevance of IDPRs in proteins that have regions of both order and disorder. This work explores these populations, by examining IDPRs in the Protein Data Bank (PDB) and in enzymes. By applying disorder prediction methods combined with an analysis of missing regions in crystal structure data ...


Inhibiting The Interaction Between Grp94 And Myocilin To Treat Primary Open-Angle Glaucoma, Andrew Stothert Jun 2016

Inhibiting The Interaction Between Grp94 And Myocilin To Treat Primary Open-Angle Glaucoma, Andrew Stothert

Graduate Theses and Dissertations

Glaucoma is a neurodegenerative protein misfolding disorder classified by increases in IOP, damage to retinal ganglion cells (RGCs), optic nerve (ON) head damage, and progressive irreversible blindness. Primary open-angle glaucoma (POAG) is the most common form of glaucoma, constituting over 90% of clinical cases. POAG is observed in patients where normal outflow channels, mainly the trabecular meshwork (TM), are exposed at the angle formed by the iris and cornea. However, due to TM cellular dysfunction, aqueous outflow resistance is increased preventing normal circulation of aqueous humor. Recent studies have shown that in 2-4% of POAG cases, increased intracellular levels of ...