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Full-Text Articles in Medicine and Health Sciences
Early Life Stress And Endothelin Receptor Type A: Separate Roles In Mediating Colitis, Rachel Q. Muir
Early Life Stress And Endothelin Receptor Type A: Separate Roles In Mediating Colitis, Rachel Q. Muir
All ETDs from UAB
Inflammatory bowel disease (IBD) results from the interplay of genetic susceptibility, environmental influences, the microbiota, and aberrant immune responses. Despite the fact that over 200 genetic susceptibility loci have been identified, the genetic contribution to disease onset is believed to be less than 50%. Environmental factors have arisen as key drivers of disease. Early life stress (ELS) is an understudied environmental trigger linked to IBD susceptibility. Utilizing 2 separate models of ELS, we show that ELS results in diminished colonic corticosterone and prolonged intestinal inflammation upon colitogenic insult. ELS-exposed animals consistently demonstrated high levels of colonic Tnf, concurrently with decreased …
Sex-Stratified Genetic Analysis Of Gout And Comorbidities, Nicholas Andrew Sumpter
Sex-Stratified Genetic Analysis Of Gout And Comorbidities, Nicholas Andrew Sumpter
All ETDs from UAB
Gout is a common inflammatory arthritis that is increasing in prevalence globally. It has clear sex differences, being more common among men, though comorbidities appear to be more common among women. It also varies in prevalence between populations, driven by a combination of genetic and socioeconomic factors. Genetic studies have identified gout-associated genetic variants, several of which are shared between different populations. Here, I combined gout-associated genetic variants into a gout polygenic risk score. This score was then used to elucidate the genetic underpinning of gout severity and presence of comorbidities, comparing its effects in different sexes and populations. I …
Biochemical Characterization Of Rna Polymerases I, Ii, And Iii And Its Therapeutic Implications, Ruth Qian Jacobs
Biochemical Characterization Of Rna Polymerases I, Ii, And Iii And Its Therapeutic Implications, Ruth Qian Jacobs
All ETDs from UAB
In contrast to Bacteria and Archaea that express a single DNA-dependent RNA polymerase (RNAP), eukaryotes express at least three structurally distinct, nuclear, DNA-dependent RNA polymerases (Pols I, II, and III) that are responsible for synthesizing all the genome-encoded RNA required by the cell. Despite the discovery of the Pols over 50 years ago, there remains a knowledge gap concerning their enzymatic properties. Over the course of evolution, we know that Pols I, II, and III have diverged in structure and function. They share a 10-subunit core and are each responsible for transcribing unique genetic loci. What remains to be understood …
Regulating Cancer Cell Metabolism During Hypoxia-Reoxygenation: Examing The Interplay Of Gasotransmitters And Glutaminolysis, Dianna L. Xing
Regulating Cancer Cell Metabolism During Hypoxia-Reoxygenation: Examing The Interplay Of Gasotransmitters And Glutaminolysis, Dianna L. Xing
All ETDs from UAB
Oxidative phosphorylation is an oxygen-dependent metabolic process that provides the majority of ATP used to support essential cellular functions. However, in cancer, limitations in oxygen availability occur during the development and metastasis of tumors. To compensate for the demands of rapidly proliferating cells, many cancers exhibit an increased demand for glycolysis, the TCA cycle, and glutaminolysis. In this thesis, extracellular flux technology and metabolomics were applied in a hypoxia-reoxygenation model to investigate the metabolic adaptations that occur in dynamic changes in oxygen and nutrient availability in cancer cells. We show the significance of glutaminolysis and its substrates in regulating cancer …
Understanding The Dual Role Of The Oncolytic Viruses And Natural Killer Cells In Targeting Neuroblastoma, Colin Harrington Quinn
Understanding The Dual Role Of The Oncolytic Viruses And Natural Killer Cells In Targeting Neuroblastoma, Colin Harrington Quinn
All ETDs from UAB
Pediatric cancer is the leading cause of death by disease in children, and neuroblastoma accounts for roughly 15% of pediatric cancer related deaths. Neuroblastoma is a malignancy of neural crest origin and develops in the ganglia of the peripheral nervous system, most commonly arising in the adrenal glands. Advancements in therapy have significantly improved outcomes for children with low-risk neuroblastoma but for those with high-risk refractory, or relapsed disease, survival outcomes remain dismal and intervention with toxic chemotherapeutics often result in long term morbidities. The need for improved therapies for this patient population is dire. Immunotherapies offer a novel approach …
Imaging Nanoscale Plasma Membrane Dynamics Reveals Diversity In Clathrin-Coated Vesicle Formation, Tomasz Jacek Nawara
Imaging Nanoscale Plasma Membrane Dynamics Reveals Diversity In Clathrin-Coated Vesicle Formation, Tomasz Jacek Nawara
All ETDs from UAB
Clathrin-mediated endocytosis (CME) is an essential cellular process facilitating the internalization of a variety of cargo. Clathrin polymerization and changes in plasma membrane architecture and composition are necessary steps to mediate the formation of clathrin-coated vesicles (CCVs). However, simultaneous analysis of clathrin dynamics and membrane structure in living cells is challenging due to the limited axial resolution of fluorescence microscopes and the heterogeneity of CME. This has fueled conflicting models of vesicle assembly and obscured the roles of flat clathrin assemblies. Here we use Simultaneous Two-wavelength Axial Ratiometry (STAR) microscopy to bridge this critical knowledge gap by quantifying the nanoscale …
Manipulation And Dependence On Host Cell Cycle By Human Rna And Dna Viruses: Human Coronavirus Oc43 And Bk Polyomavirus, Jason M. Needham
Manipulation And Dependence On Host Cell Cycle By Human Rna And Dna Viruses: Human Coronavirus Oc43 And Bk Polyomavirus, Jason M. Needham
All ETDs from UAB
Cell cycle is a universal necessity of cellular life and impacts nearly every process within the cell. However, despite over one hundred years of research, there still remain questions concerning the mechanisms and regulation of eukaryotic cell cycle. From the beginning, viruses have informed our knowledge of cell cycle. Many key regulators such as the E2F transcription factors, Src kinase, and p53 were originally discovered while studying the interactions between viruses and the cell. Herein, we continue the investigation of viral interactions with cell cycle machinery by researching an RNA virus and a DNA virus. These viruses, human coronavirus OC43 …
A Tale Of Two Waves: The Role Of Genomic Enhancers In Regulating Transcriptional And Epigenetic Responses To Neuronal Activitiy, Robert A. Phillips Iii
A Tale Of Two Waves: The Role Of Genomic Enhancers In Regulating Transcriptional And Epigenetic Responses To Neuronal Activitiy, Robert A. Phillips Iii
All ETDs from UAB
The mesolimbic dopamine (DA) pathway, which consists of dopaminergic neurons that project from the ventral tegmental area (VTA) to the nucleus accumbens (NAc), is heavily implicated in drug addiction. Exposure to drugs of abuse results in increases in extracellular concentrations of DA in the NAc, which in turn activates an immediate early gene (IEG) expression program that primarily consists of activity-dependent transcription factors, such as the AP1 subunits Fos and JunB. IEGs engage a set of temporally and functionally distinct genes, termed the late response gene (LRG) expression program. While gene expression changes are critical for drug-dependent adaptations, two major …
T-Bet Regulates The Maintenance And Asc Differentiation Potential Of The Lymph Node And Lung Memory B Cell Compartments, Christopher A. Risley
T-Bet Regulates The Maintenance And Asc Differentiation Potential Of The Lymph Node And Lung Memory B Cell Compartments, Christopher A. Risley
All ETDs from UAB
Although human memory B cells (Bmem), including extrafollicular DN2 cells and CD27+ effector Bmem (eBmem), express T-bet, its role in Bmem biology is not understood. We characterized transcriptionally distinct clusters of mature, somatically mutated nucleoprotein (NP)-specific Bmem in LNs of influenza-infected mice. None of the Bmem expressed plasma cell (PC) lineage commitment factors, but one cluster was significantly enriched for Tbx21+ cells that exhibited a molecular signature similar to the previously described human T-bet+ eBmem. Metabolic reprogramming, protein synthesis and the mTOR-dependent unfolded protein response gene networks were all upregulated in Tbx21+ NP+ mouse Bmem. Using constitutive and inducible models …
The Molecular And Structural Basis Of B Cell Epitope Targeting In Transplant Rejection, John T. Killian Jr
The Molecular And Structural Basis Of B Cell Epitope Targeting In Transplant Rejection, John T. Killian Jr
All ETDs from UAB
HLA-reactive antibodies (HLA-Abs) to mismatched polymorphic HLA molecules are one of the major barriers to successful organ transplantation. However, key knowledge gaps remain surrounding the immunology of the anti-HLA B cell response in transplant rejection. This lack of understanding regarding the phenotype and specificity of the anti- HLA B cell response means that the field cannot develop optimal therapies to treat B-cell mediated donor-specific responses and that it lacks the tools to optimally match donors and recipients to prevent rejection events. Therefore, this dissertation aimed to explore the clinical factors associated with the formation of donor-specific antibodies and the molecular …
The Long Non-Coding Rna Neat1 Mediates Astrocyte Gene Expression And Hippocampus-Dependent Memory In Aging And Alzheimer's Disease, Ashleigh Burns Irwin
The Long Non-Coding Rna Neat1 Mediates Astrocyte Gene Expression And Hippocampus-Dependent Memory In Aging And Alzheimer's Disease, Ashleigh Burns Irwin
All ETDs from UAB
Dysregulation of long non-coding RNAs (lncRNAs) is increasingly associated with cognitive dysfunction and neurodegenerative disorders such as Alzheimer’s disease (AD). The highly evolutionarily conserved lncRNA Nuclear-Enriched Abundant Transcript 1 (NEAT1) is expressed not only in a tissue- and temporally-specific manner, but also celltype specific manner. Despite the predominance of NEAT1 in glial populations, and the significant role astrocytes play in memory, relatively little is known about Neat1 regulation of astrocyte transcriptomics during age-related memory. Here, we report a crucial role of the lncRNA Neat1 in astrocyte dysfunction and memory deficits associated with both normal aging and AD. Expression of Neat1 …
Understanding Molecular Mechanisms Of Glioblastoama Resistance To Design Novel Combinatorial Therapies, Amber B. Jones
Understanding Molecular Mechanisms Of Glioblastoama Resistance To Design Novel Combinatorial Therapies, Amber B. Jones
All ETDs from UAB
Treatment options for the universally lethal brain tumor, glioblastoma (GBM), are severely limited and often unsuccessful in fully eradicating the disease. Extremely aggressive in nature, GBM cells often implore suppressive mechanisms to evade therapeutic detection which aids in the dismal 15-month median survival rate. Facilitating disease severity and more importantly, disease recurrence, are the immunosuppressive and chemoresistant phenotypes of GBM cells. Specifically, the DNA alkylating agent, temozolomide (TMZ) possesses lymphodepleting properties shunting robust immune cell infiltration into an immunologically cold tumor microenvironment. Additionally, through inherent or acquired mechanisms, GBM tumors commonly become resistant to the DNA damaging effects of TMZ …
Molecular Influences Of Racial Disparities In Pancreatic Neuroendocrine Tumors, Brendon Herring
Molecular Influences Of Racial Disparities In Pancreatic Neuroendocrine Tumors, Brendon Herring
All ETDs from UAB
Pancreatic Neuroendocrine Tumors (PNETs) are highly heterogeneous neoplasms arising from the hormone-secreting cells of the endocrine pancreas. PNETs are broadly categorized as functional and non-functional based on the presence of symptoms associated with hormone secretion, which occurs in approximately 30% of cases. While functional tumors are all considered for resection because of these symptoms and their associated sequelae, non-functional tumors > 2cm are currently resected based on increased risk of developing metastatic disease. However, this criterion is based on data from predominantly White patients. Recent studies have shown that Black patients have much higher rates of lymph node metastatic disease at …
Spatial/Temporal Zonation, Diversification, And Evolutionary Conservation Of Kidney Resident Macrophage Subpopulations In Mice And Humans After Kidney Injury, Elise Nicole Erman
Spatial/Temporal Zonation, Diversification, And Evolutionary Conservation Of Kidney Resident Macrophage Subpopulations In Mice And Humans After Kidney Injury, Elise Nicole Erman
All ETDs from UAB
In the United States, acute kidney injury (AKI) affects nearly 20% of all intensive care unit patients. Additionally, over a third of Americans aged 50 or older suffer from stage 3 chronic kidney disease (CKD) or higher. AKI and CKD are encompassing terms for many etiologies and pathological processes that affect different regions of the kidney but converge at tissue inflammation and fibrosis. Macrophages perform vital homeostatic functions and can initiate or ameliorate inflammation and fibrosis. As the largest component of the kidney immune system, kidney resident macrophages (KRMs) have been implicated in both disease propagation and mitigation, yet the …
Impact Of Arthroplasty Surgery On The Local Immune Composition Of The Knee Joint And Implications For The Periprosthetic Joint Infection, Kyle H. Cichos
Impact Of Arthroplasty Surgery On The Local Immune Composition Of The Knee Joint And Implications For The Periprosthetic Joint Infection, Kyle H. Cichos
All ETDs from UAB
The overall risk of infection after total knee arthroplasty (TKA) has not improved over the past 20 years, remaining 10-40 times greater than the risk of infection of a native knee. Despite extensive research into periprosthetic joint infection (PJI), little is known about the synovial fluid immune homeostasis of the native knee joint and how TKA surgery itself impacts the local immune composition. While many postulate a role for cartilage in maintaining this immune homeostasis, the exact method in which it contributes remains elusive. Therefore, in this dissertation I have investigated the synovial fluid changes occurring in the knee joint …
Investigating The P53 Tumor-Suppressive Network And The Dynamics/Mechanism Of P53 Loss Of Heterozygosity, Jun Wang
All ETDs from UAB
Tumor suppressor gene TP53 is the most frequently mutated gene across human cancers (~50%). Patients with Li-Fraumeni syndrome (LFS) who carry germline p53 mutations exhibit a diverse spectrum of childhood- and adult-onset malignancies. Despite over 40 years of dedicated studies to understand the role of p53 in tumor prevention, there are still many unanswered questions regarding the underlying mechanisms of p53. Previous studies have supported the notion that p53 exerts its tumor-suppressive function through its transcriptional activities. Therefore, strategies to enhance p53’s functions in tumor suppression via manipulating of downstream target gene activities in cancers show promising. To better investigate …
Cis-Regulatory Elements: Relevance For Alzheimer's Disease, Brianne Brazell Rogers
Cis-Regulatory Elements: Relevance For Alzheimer's Disease, Brianne Brazell Rogers
All ETDs from UAB
Alzheimer’s disease (AD) is the most common neurodegenerative disease, currently affecting more than six million Americans with limited treatment options. Identifying genetics contributors to neurodegenerative diseases has contributed critical insights into potential disease mechanisms. The majority of disease-associated genetic variants are located in non-coding regions, likely in regulatory elements, and affect the expression of target genes whose function contributes to neurodegeneration. Here, I performed a case-control study utilizing nuclei from dorsolateral prefrontal cortex postmortem tissue to correlate chromatin accessibility with gene expression and nominate 40,831 AD-specific candidate cis-regulatory elements. Additionally, work in this dissertation nominates ZEB1 and MAFB as candidate …
Impact Of Streptococcus Parasanguinis-Generated Reactive Nitrogen Species On Pseudomonas Aeruginosa Virulence And The Host Response, Joshua J. Baty
Impact Of Streptococcus Parasanguinis-Generated Reactive Nitrogen Species On Pseudomonas Aeruginosa Virulence And The Host Response, Joshua J. Baty
All ETDs from UAB
Streptococcus parasanguinis is an oral commensal bacterium that produces hydrogen peroxide. Hydrogen peroxide can react with endogenous molecules such as nitrite to form reactive nitrogen intermediates (RNI). These S. parasanguinis-mediated RNI have been shown to inhibit oral pathogens such as Streptococcus mutans, Enterococcus faecalis, and Aggregatibacter actinomycetemcomitans. As such, S. parasanguinis plays a protective role in the oral microbial ecosystem by antagonizing and preventing colonization by oral pathogens. In addition to being an important organism for the health of the oral cavity, S. parasanguinis has also been associated with improved outcomes for people with cystic fibrosis. There are two explanations …
The Role Of Tissue- And Cell-Type-Specific Expression And Regulation In Setbp1-Associated Diseases, Jordan Hailey Whitlock
The Role Of Tissue- And Cell-Type-Specific Expression And Regulation In Setbp1-Associated Diseases, Jordan Hailey Whitlock
All ETDs from UAB
SET binding protein 1 (SETBP1) encodes a transcription factor (TF) participating in diverse cellular processes. SETBP1 is an epigenetic hub associated with variants linked to three distinct diseases. Germline variants cause rare pediatric Schinzel Giedion Syndrome (SGS) and SETBP1 haploinsufficiency disorder (SETBP1-HD), featuring multisystemic abnormalities and neurodegeneration or milder brain issues with hypotonia, respectively. On the other hand, somatic variants contribute to hematological malignancies and adult cancer. To understand tissue-specific SETBP1 mechanisms, public RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project were analyzed. SETBP1 and targets were broadly expressed across 31 adult human tissues, revealing three distinct expression patterns: transcription …
Three Heads Are Better Than One: A Structural Look At Staphylococcal Bacteriophage Capsids, N'Toia Chivon Hawkins
Three Heads Are Better Than One: A Structural Look At Staphylococcal Bacteriophage Capsids, N'Toia Chivon Hawkins
All ETDs from UAB
Staphylococcal species such as S. aureus and S. epidermidis are opportunistic pathogens that are the leading causes of nosocomial infections. They have become of growing concern due to the virulence factors that they have acquired as well as their inability to be treated due to resistance to antibiotics. Bacteriophages have increasingly become a popular contender for eliminating these pathogens, however not every phage is suitable for the job. Size of the genome, life cycle, the ability to mobilize genomic material, and host range all factor into how well-suited a phage is to be used as a therapeutic. In this dissertation …
Primary Cilia Regulate Inflammation And Macrophage Accumulation During Injury And Cyst Formation In Mouse Pkd Models, Zhang Li
All ETDs from UAB
Polycystic kidney disease (PKD) is one of the most common inherited renal disorders. The most common form, autosomal dominant polycystic kidney disease (ADPKD), affects more than 13 million people around the world, and over 50% of them will develop end-stage renal disease (ESRD). Although ADPKD genetically is caused by mutations of PKD1 or PKD2 genes, there is increasing evidence showing that non-genetic factors such as renal injury and inflammation play important roles in cyst severity and progression in PKD. Macrophages are cells of the innate immune system known to be involved in kidney injury and repair. Data from our lab …
Induction Of Antibiotic Activity Against Methicillin-Resistant Staphylococcus Aureus In Small Molecules Through Zinc Activation, Rachel Michaela Andrews
Induction Of Antibiotic Activity Against Methicillin-Resistant Staphylococcus Aureus In Small Molecules Through Zinc Activation, Rachel Michaela Andrews
All ETDs from UAB
Methicillin-resistant Staphylococcus aureus (MRSA) is a serious human pathogen with a staggering potential for multi-drug resistance. Because of this, the Centers for Disease Control and Prevention and the World Health Organization monitor the spread of MRSA and encourage antibiotic development efforts targeting this pathogen. Despite this, few antibiotics have been developed and brought to market in recent decades. To continue treating infections caused by this organism, we must identify novel antibiotic molecules with different mechanisms of action from known antibiotics. Bacterial copper-dependent inhibitors (CDIs), molecules that become antibacterial in the presence of copper (Cu), have been studied as a novel …
The Roles Of Repressive And Activating Epigenetic Factors In Vertebrates Neural And Neural Crest Development, Saeid Mohammad Parast
The Roles Of Repressive And Activating Epigenetic Factors In Vertebrates Neural And Neural Crest Development, Saeid Mohammad Parast
All ETDs from UAB
The vertebrate nervous system comes from specific regions of the ectoderm that comprises of the neural plate and the neural crest. Although genetic mechanisms governing vertebrate neural development have been investigated in depth, there is a knowledge gap regarding the roles of epigenetic mechanisms in this process. As epigenetic modulators, the COMPASS (also known as SET1/MLL complex) and HP1 proteins are responsible for regulating chromatin accessibility to transcription factors. COMPASS is responsible for deposition of activating histone H3K4 methylation marks at promoters and enhancers and thus creates open chromatin domains. The critical structural and regulatory subunits of COMPASS, Dpy30 and …
Regulation Of Stromal Cells Through Inflammatory Signalling, Victoria Matkins
Regulation Of Stromal Cells Through Inflammatory Signalling, Victoria Matkins
All ETDs from UAB
The bone marrow is a complex organization of hematopoietic and nonhematopoietic cells that form niches to maintain systemic homeostasis during stress and disease. Stromal cells are non-hematopoietic cells first proposed in 1978 in the bone marrow to be essential for hematopoietic stem cells (HSC). Since then, mesenchymal stromal cells (MSC) have been shown to be critical for the HSC self-renewal, retention, and differentiation through chemokines, cytokines, and adhesion molecules. However, like HSCs, MSCs are multipotent progenitors that differentiate into osteoblasts, adipocytes, and chondrocytes to from tissues of the skeletal, endocrine, and connective systems. These multipotent progenitors are tightly regulated in …
The Role Of Protein Translation And Degradation In Aging And Alzheimer Disease Pathogenesis, Harper S. Kim
The Role Of Protein Translation And Degradation In Aging And Alzheimer Disease Pathogenesis, Harper S. Kim
All ETDs from UAB
Protein translation (PT) is an essential cellular process playing crucial roles in growth and development. PT precipitously declines with age in multiple animal species, including humans. It has been implicitly assumed that elevated PT at young ages is beneficial to health while PT ends up dropping as a passive byproduct of aging. However, whether this holds true and how dynamic fluctuations in PT over time impact aging remain unknown. In Drosophila, we show that a transient PT spike in early-adulthood drives aging by triggering dysfunction in protein homeostasis (proteostasis) at old ages. We propose the early-adulthood spike in PT to …
Transcriptional Regulation Of Metabolism And Synaptic Function In Neurons, Stephanie N. Fox
Transcriptional Regulation Of Metabolism And Synaptic Function In Neurons, Stephanie N. Fox
All ETDs from UAB
Mitochondrial dysfunction, transcriptional dysregulation, and protein aggregation are all unifying features of neurodegenerative disorders, including Parkinson’s Disease. Parkinson’s Disease is a debilitating movement disorder with no known cure, leading sci-entists to explore the underlying etiological contributors to neuronal dysfunction and loss to devise strategies for neuroprotection. Estrogen-related receptor gamma (ERRγ) is a member of a family of transcription factors which regulate the expression of mitochondrial genes. To determine whether ERRγ modulation can provide insight into transcriptional and mitochondrial dysfunction with neurodegeneration, the experiments in this thesis project determined 1) the importance of transcription of mitochondrial genes in disease as regu-lated …
Distinct Clinical Manifestations Associated With Autoantibodies And Cytokines In Systemic Lupus Erythematosus, Fatima K. Alduraibi
Distinct Clinical Manifestations Associated With Autoantibodies And Cytokines In Systemic Lupus Erythematosus, Fatima K. Alduraibi
All ETDs from UAB
Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by production of autoantibodies (autoAbs) and cytokines. Moreover, lupus nephritis (LN) occurs in approximately 50% of SLE patients. AutoAb and cytokine levels produced by B and T cells are high in LN patients, although their relationship with histological patterns requires investigation. Methods: We analyzed the relationship between B cell cytokines and major T cell cyto-kines, including their association with autoAbs, and the clinical manifestations of SLE, especially LN. We also analyzed endogenous intracellular interferon beta (IFNβ) expression in the peripheral blood mononuclear cells and serum circulating nephritogenic autoAbs from …
Targeting The Frataxin Transcriptional Defect As A Therapeutic Approach For Friedreich's Ataxia, Anna Maria Schreiber
Targeting The Frataxin Transcriptional Defect As A Therapeutic Approach For Friedreich's Ataxia, Anna Maria Schreiber
All ETDs from UAB
Friedreich’s ataxia (FRDA) is the most common inherited ataxia worldwide. This autosomal recessive neurodegenerative disorder manifests in the central and peripheral nervous system but also affects the cardiovascular and endocrine systems. No effective treatment is available. FRDA is caused by expansion of GAA repeat tracts in intron 1 of the frataxin (FXN) gene on both alleles. An inverse correlation between FXN levels and GAA repeat length exists. Frataxin is a mitochondrial protein participating in iron-sulfur (Fe-S) cluster formation. Frataxin deficiency results in reduced activity of Fe-S-containing enzymes involved in critical biological processes, such as cellular respiration and DNA repair. Expansion …
Applying Pet Imaging To Cancer Immunotherapy To Improve Clinical Outcomes, Kirsten M. Reeves
Applying Pet Imaging To Cancer Immunotherapy To Improve Clinical Outcomes, Kirsten M. Reeves
All ETDs from UAB
The use of biomarkers has significantly enhanced patient outcome by improving diagnosis, personalizing therapy, and monitoring therapeutic response yet most cancers remain non-responsive. Thus, there is a need to better understand the underlying biological mechanisms and tumor microenvironment to enhance therapeutic efficacy. Molecular imaging, including magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) are used to assess response during oncology therapy. Molecular imaging can also provide a noninvasive approach to accurately quantify biomarkers correlated with the tumor microenvironment, including glucose metabolism and hypoxia. 18F-Fluoromisonidazole (18F-FMISO) hypoxia targeted cellular uptake has been shown to correlate with negative …
The Role Of Dock3 In Normal Skeletal Muscle Function And Metabolism, Adrienne Samani
The Role Of Dock3 In Normal Skeletal Muscle Function And Metabolism, Adrienne Samani
All ETDs from UAB
DOCK (dedicator of cytokinesis) are proteins of an 11-member family of typical guanine exchange factors (GEFs) expressed almost exclusively in the brain and spinal cord. Human pathogenic DOCK3 variants have been identified to cause debilitating neuromuscular phenotypes such as muscle hypotonia, ataxia, and intellectual disability. Our lab identified DOCK3 as being strongly upregulated in Duchene muscular dystrophy (DMD), specifically in the skeletal muscles of DMD patient and mouse skeletal muscles. Global Dock3 KO mice on the dystrophin-deficient background exacerbated skeletal muscle and cardiac phenotypes. Similarly, DOCK3 KO mice appeared to have poor muscle architecture, locomotive activity, reduced myogenic fusion, impaired …