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Articles 1 - 30 of 53
Full-Text Articles in Medicine and Health Sciences
Dopamine-Dependent Transcriptional Dynamics In Striatal Physiology And Cocaine Reward, Morgan Elizabeth Zipperly
Dopamine-Dependent Transcriptional Dynamics In Striatal Physiology And Cocaine Reward, Morgan Elizabeth Zipperly
All ETDs from UAB
Exposure to drugs of abuse alters transcriptional programs and neuronal activity, leading to long-lasting cellular and behavioral adaptations that may contribute to addiction. The nucleus accumbens (NAc), part of the mesocorticolimbic dopamine pathway, plays a central role in motivation, reward, and reward-related learning, and this brain region is highly implicated in the development and maintenance of addiction. However, the specific contributions of defined cell populations in the NAc to drug reward processes is still poorly understood. Here, we used electrophysiological, optogenetic, and single-nucleus RNA-sequencing (snRNA-seq) approaches in a rodent model system to define the acute physiological and transcriptional responses of …
Downstream Pathways Of Glucagon Receptor Agonism In Obesity, Shelly Nason
Downstream Pathways Of Glucagon Receptor Agonism In Obesity, Shelly Nason
All ETDs from UAB
Obesity is highly prevalent and strategies to improve weight loss maintenance are critical for healthcare. Behavioral interventions are effective but require major lifestyle changes that are often difficult to maintain long-term. Therefore, modifying energy balance with pharmacotherapy is a strategy to combine with lifestyle modifications for sustained weight loss. Glucagon, a hormone involved in maintaining glucose homeostasis, also regulates energy expenditure, food intake, and lipid metabolism. As such, glucagon-based therapies have gained attention as an attractive clinical target. Glucagon Receptor (GCGR) mono-agonism induces glucose intolerance; therefore, dissecting the mechanisms by which GCGR signaling mediates energy balance are clinically relevant to …
Rab27 And 14-3-3 Mediated Regulation Of Alpha-Synuclein Pathology, Rachel Nicole Underwood
Rab27 And 14-3-3 Mediated Regulation Of Alpha-Synuclein Pathology, Rachel Nicole Underwood
All ETDs from UAB
Alpha-synuclein (αsyn) is the key component of proteinaceous aggregates termed Lewy Bodies (LBs) that pathologically define a group of disorders known as synucleinopathies, including Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). αSyn is thought to misfold and spread throughout the brain in a prion-like fashion. Transmission of αsyn necessitates the release of misfolded αsyn from one cell and the uptake of that αsyn by another, in which it templates the misfolding of endogenous αsyn. Identifying regulators of this process is essential to understanding how αsyn propagates and furthers disease progression. In this study, we investigated Rab27 and 14-3-3θ …
Understanding And Targeting Glucose Transporter 3 In Glioblastoma, Catherine Jeanne Libby
Understanding And Targeting Glucose Transporter 3 In Glioblastoma, Catherine Jeanne Libby
All ETDs from UAB
Glioblastoma (GBM) is the most common adult primary malignant brain tumor with a median survival of about 15 months, even after aggressive treatment. Treatment of GBM is difficult for multiple reasons including the location of the tumor, tumor invasiveness, and the high degree of both inter-and intra-tumoral heterogeneity. Contributing to intratumoral heterogeneity are highly tumorigenic, stem-like tumor cells, with the capacity to self-renew and propagate the tumor, termed brain tumor initiating cells (BTICs). BTICs are also commonly therapy resistant, highly invasive, and metabolically plastic with elevated expression of glucose transporter 3 (GLUT3) allowing them to preferentially survive in low nutrient …
From Pathology To Circuits: Loss Of Pink1 Function In Parkinson’S Disease, Rose Berthe Creed
From Pathology To Circuits: Loss Of Pink1 Function In Parkinson’S Disease, Rose Berthe Creed
All ETDs from UAB
Parkinson’s disease (PD) is the most common neurogenerative motor disorder, affecting over 10 million people worldwide. Clinically, PD is diagnosed by presentation of hypokinetic movements such as bradykinesia, rigidity, and resting tremor. Additionally, PD patients have non-motor symptoms that include anosmia, constipation, and hypophonia. Current therapeutics have been successful in treating many of the locomotor symptoms, however no therapies stop or slow disease progression and the effectiveness of current medications diminishes as the symptoms invariably become more severe over the course of many years. Histopathologically, PD diagnosis is confirmed postmortem by two pathological hallmarks: 1. loss of dopaminergic neurons in …
T Cells In Synucleinopathies, Gregory Paul Williams
T Cells In Synucleinopathies, Gregory Paul Williams
All ETDs from UAB
Synucleinopathies, which include Parkinson disease (PD), dementia with Lewy Bodies (DLB), and multiple system atrophy (MSA), are a collection of neurodegenerative diseases that are in major part defined by the presence of alpha-synuclein (α-syn) rich protein aggregates in the brain. Increasing evidence has highlighted a neuroinflammatory phenotype also associated with these synucleinopathies. This neuroinflammatory phenotype includes the activation of central nervous system (CNS) microglia, increased pro-inflammatory cytokines, and the infiltration of peripheral T cells into the CNS. We sought to further explore the T cell responses associated with PD and MSA. Using two preclinical mouse models of PD and MSA, …
Role Of Endogenous Tau In Lewy-Like Pathology, Lindsay Stoyka
Role Of Endogenous Tau In Lewy-Like Pathology, Lindsay Stoyka
All ETDs from UAB
Lewy Body Diseases (LBDs) are a group of disorders characterized by intracellular inclusions of misfolded alpha-synuclein (α-synuclein). Of these, Parkinson’s Disease (PD) is the most common neurodegenerative movement disorder, and Dementia with Lewy Bodies (DLB) is the second most common neurodegenerative dementia. PD is characterized clinically by bradykinesia, resting tremor, rigidity, and postural instability. In addition, up to 80% of patients eventually develop dementia, termed Parkinson’s Disease Dementia (PDD). DLB is characterized by onset of dementia before or concurrently with parkinsonism. Currently, no disease-modifying therapies exist for either of these diseases. Lewy pathology is found in regions important for cognition …
Gene–Environment Interaction In Parkinson Disease: The Gut Microbiome, Zachary D. Wallen
Gene–Environment Interaction In Parkinson Disease: The Gut Microbiome, Zachary D. Wallen
All ETDs from UAB
GENE–ENVIRONMENT INTERACTION IN PARKINSON DISEASE: THE GUT MICROBIOME ZACHARY D. WALLEN GENETICS, GENOMICS, AND BIOINFORMATICS ABSTRACTParkinson disease (PD) is a progressive neurodegenerative disease with no cure. Majority of cases are idiopathic, and the cause is unknown. Studies have been conducted in human and animals to identify PD risk factors, resulting in a list of genetic and environmental factors that modestly increases risk of PD. Still, no individual risk factor fully explains the cause of PD, and neither has the combination of these factors. Additional avenues of research are being investigated to find potential triggers of PD, and factors that might …
Lim Transcriptional Complexes That Impact Endocrine Pancreas Development And Function, Maigen Bethea
Lim Transcriptional Complexes That Impact Endocrine Pancreas Development And Function, Maigen Bethea
All ETDs from UAB
The Ldb1:Isl1 LIM transcriptional complex is critical for endocrine pancreas development as well as b-cell terminal differentiation. These complexes have been shown to interact with various proteins to elicit transcriptional regulation in other tissues, yet few interactors have been identified in b-cells. Therefore, the objective of this dissertation was to identify interactors of Ldb1 and Isl1 and assess their contributions to endocrine pancreas development and function. Using a reversible crosslink immunoprecipitation (ReCLIP) and mass spectrometry (MS) strategy to isolate endogenous Ldb1 and/or Isl1 interacting protiens, SSBP3, Rnf20, and Rnf40 (E3 ubiquitin ligases) coregulators were identified. SSBP3 was found to interact …
Immunopathogenesis In Fungal Asthma, Matthew Stephen Godwin
Immunopathogenesis In Fungal Asthma, Matthew Stephen Godwin
All ETDs from UAB
Asthma patients are increasingly presenting with asthma that is more difficult to control and treat than in years past. A subset of these patients who are sensitive to fungal species are described as having severe asthma with fungal sensitization (SAFS). Given the severity of disease, there is ever increasing interest in identifying the immune processes underlying SAFS disease pathology and the development of novel therapeutics to improve management. While sensitivity to multiple fungal species has been described in SAFS, none is more common than Aspergillus fumigatus. Here, we describe two previously unrecognized contributors to the amelioration of disease pathology in …
Gp44, A Minor Protein With A Major Role In Bacteriophage 80Α Infection, Keith Allen Manning
Gp44, A Minor Protein With A Major Role In Bacteriophage 80Α Infection, Keith Allen Manning
All ETDs from UAB
Bacteriophage 80α is a temperate double-stranded DNA phage that infects Staphylococcus aureus and is capable of mobilizing a variety of mobile genetic elements named S. aureus Pathogenicity Islands. The capsid of the mature virion is composed of subunits of the capsid protein, portal protein, and a minor capsid protein gp44 as well as packaged phage genomic DNA. The loss of the gp44 protein completely eliminates the phage titer of 80α but does not eliminate the transduction of the pathogenicity islands. In this dissertation, I show that the minor capsid protein is primarily active in a post-ejection role. Without gp44 the …
Disease Specific Dysregulation Of Stat1 And Stat5 Activation In Mature Cd4+ And Cd8+ T Cells Influences Enhanced Kinetic Responses And Inflammation In Patients With Treatment-Naïve Relapsing Remitting Multiple Sclerosis (Rrms), Brandon Jay Pope
All ETDs from UAB
Autoimmunity is propagated through the lack of effective mechanisms of central and peripheral tolerance. In relapsing remitting multiple sclerosis (RRMS), dysregulated adaptive immune cells have been shown to contribute to disease morbidity through the influence of immune-modulating cytokines in the peripheral blood. Interleukin-2 (IL-2) is a cytokine with several key functions in regulating homeostatic mechanisms within the human immune system. Interferon gamma (IFNγ) is a type II interferon that is needed for an effective response to intracellular bacteria infection through the actions of Th1 cells. IL-2 and IFNγ signaling occurs primarily through signal transducer and activator of transcription (STAT) activation. …
Investigating The Roles Of The Renal Primary Cilium Through The Use Of Intravital Imaging, Dustin Zachary Revell
Investigating The Roles Of The Renal Primary Cilium Through The Use Of Intravital Imaging, Dustin Zachary Revell
All ETDs from UAB
Primary cilia are small microtubule based appendages present on nearly every cell type in the mammalian body, and are highly conserved from organisms as simple as algae to humans. Cilia function as complex signaling centers integrating a variety of pathways and play critical roles throughout development and in maintaining homeostasis. Mutations to ciliary proteins in humans result in a wide array of diseases termed ciliopathies, which have a broad range of symptoms affecting nearly every organ in the body. Renal primary cilia are present on the apical side of tubular epithelium, where they project into the lumen and are thought …
Novel Mechanisms Of Nitric Oxide Activation In The Kidney, Randee Sedaka
Novel Mechanisms Of Nitric Oxide Activation In The Kidney, Randee Sedaka
All ETDs from UAB
Globally, adult sodium consumption has far exceeded daily intake recommendations, leading to one in ten cardiovascular deaths. Given the rise in hypertension prevalence, uncontrolled hypertension with antihypertensive medication use, and significant associations between high salt intake and high blood pressure, there is a need to better understand the mechanisms involved in hypertension. Nitric oxide synthase 1 (NOS1) is a well-established regulator of fluid and electrolyte balance in the renal collecting duct (CD) with highest activity in the inner medulla (IM). We previously reported that high salt (HS) intake stimulates CD endothelin B receptor (ETBR)/NOS1-dependent generation of NO, thereby inhibiting the …
Diurnal Dysfunction In Control Of Sodium Excretion In Diet-Induced Obesity, Reham Soliman
Diurnal Dysfunction In Control Of Sodium Excretion In Diet-Induced Obesity, Reham Soliman
All ETDs from UAB
The renal endothelin system plays a key role in sodium excretion, particularly under high salt (HS) diet. HS stimulates renal endothelin-1 (ET-1), which binds and activates the endothelin receptor B (ETB) to excrete the excess salt. Loss of ETB receptor is linked to the development of hypertension under HS. Central clock genes are important in maintaining rhythmic patterns of sodium excretion and ET-1 is identified as a target for clock genes, including Period and Bmal1. ET-1 excretion follows a diurnal rhythm along with sodium excretion. Sexual dimorphism is evident in the diurnal regulation of endothelin-mediated natriuresis and its downstream targets. …
Enhancer Rnas As Regulators Of Gene Expression And Neuronal Function, Nancy Verena Nicole Carullo
Enhancer Rnas As Regulators Of Gene Expression And Neuronal Function, Nancy Verena Nicole Carullo
All ETDs from UAB
Genomic enhancers are cis-regulatory elements in the DNA that exhibit spatial and temporal control over intricate gene expression programs shaping fate and function of heterogeneous cell populations in the developing and adult brain. In addition to their role in cellular development and maintenance, enhancer activity drives transcriptional changes in response to stimulation. Active enhancers are subject to bidirectional transcription that yields non-coding enhancer RNAs (eR-NAs). However, the functional role of eRNAs in transcriptional regulation remains controversial. Therefore, we used primary neuronal cultures to investigate en-hancers and eRNAs in the rat genome. We identified and verified enhancer-gene pairs, characterized their response …
Toxin Secretion By Mycobacterium Tuberculosis, Uday Tak
Toxin Secretion By Mycobacterium Tuberculosis, Uday Tak
All ETDs from UAB
Mycobacterium tuberculosis (Mtb) is a highly infectious airborne bacterial pathogen, and the causative agent of human tuberculosis. Mtb infects approximately one-third of the human population, and is responsible for more deaths than any other infectious disease in the history of mankind. Mtb is an intracellular pathogen and primarily infects myeloid cells, such as macrophages in the human lung. In macrophages, Mtb establishes a replication niche within membrane-bound vacuoles named phagosomes, while subverting immunity. The intracellular survival of Mtb depends on manipulation of host cellular processes through secreted effector proteins. Ultimately, this intracellular vacuole is ruptured by the type VII secretion …
Copper Dependent Inhibitors Subvert Common Resistance Mechanisms In Staphylococcus Aureus And Inhibit Crucial Metabolic Pathways, Cameron Crawford
Copper Dependent Inhibitors Subvert Common Resistance Mechanisms In Staphylococcus Aureus And Inhibit Crucial Metabolic Pathways, Cameron Crawford
All ETDs from UAB
The effective antibiotic pool is shrinking with antibiotic resistance a constant problem that threatens to make our current therapies obsolete. To combat this, new drug screening methodologies are required since the traditional drug screens are offering limited results or only improvements upon current treatments. This work expands upon the idea that transition metal toxicity can be preferentially targeted towards bacteria. Specifically, the focus is on copper dependent inhibitors that quickly work to eliminate Staphylococcus aureus. S. aureus is a particularly threatening bacteria with high strain variability, a litany of survival and virulence factors, and multiple drug resistance mechanisms that are …
Structural And Biophysical Investigations Into The Mechanism Of Hiv-1 Envelope Incorporation, Richard Elliot Murphy
Structural And Biophysical Investigations Into The Mechanism Of Hiv-1 Envelope Incorporation, Richard Elliot Murphy
All ETDs from UAB
Recent advancements in drug therapies and patient care have drastically improved upon the mortality rates of HIV-1 infected individuals. Many of these therapies were developed or improved upon using structure-based techniques, which underscores the importance of obtaining atomic level structural data critical to the understanding of essential mechanisms in the replication cycle of HIV-1. One such process which remains poorly understood on the structural level is the incorporation of the envelope glycoprotein (Env) into budding virus particles. The Env protein mediates viral infection of host cells, and there is strong evidence suggesting that incorporation of Env is mediated by an …
Contribution Of Adaptive Immune Responses In Chronic Lung Diseases, Thi Kim Tran-Nguyen
Contribution Of Adaptive Immune Responses In Chronic Lung Diseases, Thi Kim Tran-Nguyen
All ETDs from UAB
Immune dysregulation is a hallmark of various chronic lung diseases such as Chronic Obstructive Pulmonary Diseases (COPD) and Idiopathic Pulmonary Fibrosis (IPF). Previous studies in our lab have shown evidences of autoimmunity such as increases in autoantibodies, abnormal T cell profile, immune complex deposition and the presence of ectopic lymphoid structures in the lung of these patients. This thesis consolidates two separate projects about various aberrant immune responses in these diseases. The first project identified Glucose-Regulated-Protein 78 (GRP78) as the common autoantigen in COPD and characterized how GRP78 autoantibodies may increase COPD mortality via its atherogenic effects. I demonstrated that …
Cd8 T-Cell Responses To A Diverse Virus: Adaptation And Cross-Reactivity In Hiv Vaccination, Sushma Boppana
Cd8 T-Cell Responses To A Diverse Virus: Adaptation And Cross-Reactivity In Hiv Vaccination, Sushma Boppana
All ETDs from UAB
In the four decades since human immunodeficiency virus (HIV) was discovered, significant progress has been made in treating HIV infection and in understanding the viral and immune dynamics underlying disease pathogenesis. However, in spite of scientific advances, HIV remains a significant global health issue, and an effective preventative vaccine has yet to be created. Many groups have demonstrated the importance of CD8 T cells in viral control during natural HIV infection and believe that CD8 T cells could contribute to vaccine efficacy by alleviating disease course in individuals who became infected despite vaccination. One major obstacle to inducing potent CD8 …
Rna Polymerase I Elongation Kinetics: A Biochemical And Global Study Of A Cancer Therapeutic Target, Catherine Elizabeth Scull
Rna Polymerase I Elongation Kinetics: A Biochemical And Global Study Of A Cancer Therapeutic Target, Catherine Elizabeth Scull
All ETDs from UAB
My graduate research has focused on understanding the elongation kinetics of RNA polymerase I (Pol I), the enzyme responsible for synthesizing ribosomal RNA (rRNA), and defining how inhibition of ribosome biogenesis may be used as a cancer therapeutic strategy. Here, I have defined key biophysical features of Pol I and I have expanded the field’s understanding of Pol I elongation by: 1) characterizing the enzymatic properties of Pol I by mutational analysis of the polymerase itself, and by 2) elucidating the role of DNA sequence on Pol I arrest and nucleolytic cleavage activity. In recent years, Pol I has become …
Structural Studies Of Rna Synthesis Machinery In Vesicular Stomatitis Virus, Joseph Ryan Gould
Structural Studies Of Rna Synthesis Machinery In Vesicular Stomatitis Virus, Joseph Ryan Gould
All ETDs from UAB
Vesicular stomatitis virus (VSV) is a member of the order Mononegavirales, which is comprised of viruses with genomes of non-segmented negative sense RNA. Many fundamental insights into the molecular biology of mononegaviruses were first made in VSV, such as the unique viral RNA synthesis template comprised of the nucleocapsid (N) protein and genomic RNA and the distinctive large (L) protein which contributes all enzymatic activities of RNA synthesis and transcript maturation. The L protein performs its enzymatic functions in concert with the phosphoprotein (P), a flexible, charged, and phosphorylated cofactor. The goal of the research presented in this dissertation was …
Il-17 Producing Cd4 T Cells In Spontaneous Germinal Center And Autoantibody Formation In Murine Lupus, Huixian Hong
Il-17 Producing Cd4 T Cells In Spontaneous Germinal Center And Autoantibody Formation In Murine Lupus, Huixian Hong
All ETDs from UAB
IL-23 promotes autoimmune disease, including Th17 CD4 T-cell development and autoantibody (autoAb) production. Here, we show that a deficiency of the p19 component of IL-23 in the autoimmune BXD2 (BXD2-p19−/−) mouse leads to a shift of the follicular T-helper cell program from Tfh-IL-17 to Tfh-IFN-ɣ. Although the germinal center (GC) size and the number of GC B cells remained the same, BXD2-p19−/− mice exhibited a lower class-switch recombination (CSR) in the GC B cells, leading to lower serum levels of IgG2b. Single-cell transcriptomics analysis of GC B cells revealed that while Ifngr1, Il21r and Il4r genes exhibited a synchronized expression …
Pharmacodynamic Responses And Efficacies Associated With Lrrk2 Inhibition, Kaela Kelly
Pharmacodynamic Responses And Efficacies Associated With Lrrk2 Inhibition, Kaela Kelly
All ETDs from UAB
Parkinson’s disease (PD) is an age-related, progressive, movement disorder pathologically characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of proteinaceous aggregates, termed Lewy bodies, that are largely comprised of αSynuclein (αSyn). Missense mutations in the leucine-rich repeat kinase (LRRK2) gene are the most common genetic cause of PD and lead to gain-of-function increases in kinase activity. The G2019S-LRRK2 mutation is the most frequent mutation and elevates kinase activity by ~2-3 fold. Genetic and biochemical evidence suggest elevated LRRK2 kinase activity plays a pathogenic role in the development of PD, implicating LRRK2 …
Elucidating The Role Of Hedgehog Signaling In Tumor Cell Response To Dna Damage And Microenvironmental Stress, Tshering Dolma Lama-Sherpa
Elucidating The Role Of Hedgehog Signaling In Tumor Cell Response To Dna Damage And Microenvironmental Stress, Tshering Dolma Lama-Sherpa
All ETDs from UAB
Hypoxia within solid tumors presents as a barrier to the effectiveness of cancer treatment. Hypoxia has been implicated in cancer cell resistance to standard therapies used in the clinic to treat breast cancer. Additionally, the treatment resistance mechanisms in cancer cells are exacerbated by oncogenic pathways that enable adaptation to the hypoxia and facilitate therapy resistance. Cancer cells often co-opt signaling pathways essential for embryonic development as a defense against cellular attacks. Hedgehog (Hh) signaling pathway is one of such embryonic development pathways that have been implicated in mitigating cancer growth, metastasis, and resistance to therapy. Hh signaling pathway promotes …
Protective Host Responses During Acute And Chronic Lung Exposure To Aspergillus Fumigatus, Joseph Mackel
Protective Host Responses During Acute And Chronic Lung Exposure To Aspergillus Fumigatus, Joseph Mackel
All ETDs from UAB
Aspergillus fumigatus is an environmental airborne fungus that acts as both an opportunistic pathogen and an allergen. In immunocompromised hosts, A. fumigatus can germinate in the lung, cause tissue damage and pneumonia, and disseminate to other organs, causing a disease termed invasive aspergillosis (IA). In severe asthma, sensitization to fungi such as A. fumigatus is associated with more severe disease. Determination of host and fungal factors that drive immunoprotection versus immunopathogenesis in both of these settings will ultimately enable therapeutic modulation of immune responses to improve disease outcomes. In this body of work, we build on recent findings that implicate …
Deficiency Of Tumor Suppressor Merlin Induces Metabolic Reprogramming In Breast Cancer, Mateus Mota
Deficiency Of Tumor Suppressor Merlin Induces Metabolic Reprogramming In Breast Cancer, Mateus Mota
All ETDs from UAB
The tumor suppressor Merlin is encoded by Neurofibromin 2 (NF2) gene. Merlin is predominantly located in the cell cortex where regulates cell proliferation by mediating cell contact-dependent growth inhibition. Metastatic breast cancer tissues presented with a remarkable loss of Merlin protein, revealing clinical relevance of Merlin. In order to examine the cellular effect of Merlin deficiency, breast cancer cell lines were silenced for NF2. Additionally, to assess the impact of Merlin loss at the organismal level, a mammary-specific NF2 knockout mouse mammary tumor model was engineered. Merlin deficiency induced a metabolic shift from mitochondrial oxidative phosphorylation to aerobic glycolysis. Furthermore, …
Understanding The Impact Of Diet And Obesity On Anti-Tumor Immunity And Therapeutic Efficacy In Kidney Cancer, Rachael Miller Orlandella
Understanding The Impact Of Diet And Obesity On Anti-Tumor Immunity And Therapeutic Efficacy In Kidney Cancer, Rachael Miller Orlandella
All ETDs from UAB
Obesity is regarded as a major risk factor for developing renal cell carcinoma (RCC). Advanced-stage RCC exhibits chemotherapeutic resistance, but is responsive to immunotherapies such as the immune checkpoint inhibitor anti-programmed cell death-1 (anti-PD-1). Despite some clinical successes, response rates remain low for anti-PD-1 monotherapy (20-30%). Preclinical evaluations of immunotherapeutic strategies typically use lean mice and do not account for patient comorbidities. This may explain the underwhelming success rates following clinical translation of new cancer treatments. Recent studies found that obesity was associated with favorable outcomes and responses to immunotherapy in melanoma. However, the effects of obesity on anti-tumor immunity …
Advancing Single Cell And Crispr/Dcas9 Technologies For The Study Of Reward Learning And Addiction, Corey Grant Duke
Advancing Single Cell And Crispr/Dcas9 Technologies For The Study Of Reward Learning And Addiction, Corey Grant Duke
All ETDs from UAB
Drug addiction is a chronic relapsing condition inflicting tremendous harm to individuals and society with ineffective treatment options available to most people. Drugs of abuse elevate dopamine levels in a brain region known as the nucleus accumbens (NAc), and activate gene programs considered essential for producing lasting synaptic and cell state changes which underlie the generation of addictive behavior. These gene expression changes remain poorly understood due to a complex heterogenous cellular architecture, and the rapidly fluctuating nature of the transcriptional processes themselves which make investigation difficult. Recent technical advances increase access to both profiling and manipulating these transcriptional changes …