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Full-Text Articles in Medicine and Health Sciences
The Role Of Mitochondria And Plasma Membrane Ca2+ Transport Systems In Ca2+-Dependent Glutamate Release From Rat Cortical Astrocytes, Reno Cervo Reyes
The Role Of Mitochondria And Plasma Membrane Ca2+ Transport Systems In Ca2+-Dependent Glutamate Release From Rat Cortical Astrocytes, Reno Cervo Reyes
All ETDs from UAB
Astrocytes, a type of glial cell in the central nervous system, are recognized for their support roles to neurons. They supply neurons with metabolites, maintain ion homeostasis and clear the synaptic space of neurotransmitters. However, it has been found that some astrocytes have receptors for neurotransmitter and neuroligands, exhibit Ca2+ excitability when stimulated via these receptors, and secrete gliotransmitters as an output of this Ca2+ excitability. In the Ca2+-dependent release of glutamate, it has been shown that the endoplasmic reticulum is the predominant source and the extracellular space is the auxiliary source of free Ca2+ necessary for triggering exocytosis. Because …
Mechanisms Of Growth Hormone Action In Skeletal Muscle, Mahendra Devaraj Mavalli
Mechanisms Of Growth Hormone Action In Skeletal Muscle, Mahendra Devaraj Mavalli
All ETDs from UAB
Growth hormone (GH) and insulin like growth factor-1 (IGF-1) exert profound growth promoting actions during pre and postnatal skeletal muscle development. GH and IGF-1 seem to promote their anabolic actions by influencing skeletal muscle cell prolif-eration and fusion. However, because GH stimulates the production of IGF-1 from the liver and other GH-responsive peripheral tissues, including skeletal muscle, the individual contributions of these two growth factors to anabolic responses in skeletal muscle remains poorly defined. In this dissertation research, I sought to distinguish the mechanisms responsible for growth hormone's (GH) anabolic actions in skeletal muscle. To accomplish this, I analyzed the …
The Essential Role Of Macrophages And Tlr Signaling In The Host Response To Mycoplasma Pneumoniae, Jen-Feng Lai
The Essential Role Of Macrophages And Tlr Signaling In The Host Response To Mycoplasma Pneumoniae, Jen-Feng Lai
All ETDs from UAB
Several reports have suggested that Mycoplasma pneumoniae (Mp) can contribute importantly to the expression of symptoms in asthmatic human subjects. As a foundation for understanding the interactions between Mp and asthma susceptibility, we first studied the mechanisms by which the host normally eliminated Mp. Mice were inoculated with 4x106 Mp intranasally. Twenty-four hours after inoculation with Mp, subpopulations of CD11b+ macrophages/monocytes had been recruited into the lungs. The clearance of Mp was impaired both in macrophage-depleted and in macrophage-deficient mice. Furthermore, mice deficient in MyD88, a major adaptor for TLR signaling, showed dramatically defective clearance of Mp, associated with reduced …
Identification And Characterization Of Virulence Factors Of Mycoplasmas, Wenyi Luo
Identification And Characterization Of Virulence Factors Of Mycoplasmas, Wenyi Luo
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Mycoplasmas cause a group of diseases that are characterized by their chronicity and resistance to treatment. Diseases caused by the murine pathogens Mycoplasma pulmonis and Mycoplasma arthritidis are often studied as models of human diseases caused by a variety of chronic pathogens that induce a similar pathology. Among several candidate pathogenic factors, superantigens and degradative enzymes such as glycosidases are potentially important but not well characterized. The M. arthritidis mitogen (MAM) is a superantigen secreted by M. arthritidis. Its role with respect to arthritogenicity and toxicity is unclear. To improve the efficiency of transformation and hence enhance efforts to generate …
Understanding The Regulatory Mechanisms Of Ubp-M And H2a Deubiquitination In Chromatin And Cellular Functions, Heui Yun Joo
Understanding The Regulatory Mechanisms Of Ubp-M And H2a Deubiquitination In Chromatin And Cellular Functions, Heui Yun Joo
All ETDs from UAB
Posttranslational modifications of histones regulate important chromatin and cellular functions. Among them, ubiquitination of histone H2A is correlated to transcriptional repression, such as HOX gene silencing and X chromosome inactiviation. Little was known about the removal of ubiquitin from histones, the enzyme(s) involved and its function in chromatin dynamics. We have identified the protein Ubp-M (USP16) to be the H2A- and nucleosome-specific deubiquitinase. We also demonstrated that Ubp-M-mediated H2A deubiquitination is involved in cell cycle progression to M-phase, HOX gene expression, and posterior development in Xenopus laevis. Furthermore, we have also purified USP12 and USP46 which contain an Ubp-M independent …
Characterization Of The Induction And Regulation Of Early B Cell Development, Melissa Ann Thal
Characterization Of The Induction And Regulation Of Early B Cell Development, Melissa Ann Thal
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Hematopoiesis is a highly regulated process directed by the microenvironment or niche in the bone marrow and the transcription factors those signals activate. Gene knockout experiments have identified critical cytokine signals and transcription factors required for promoting the differentiation of a hematopoietic stem cell to a B cell, but the regulatory mechanisms have yet to be fully elucidated. In early B cell development, a transcriptional hierarchy exists wherein E2A proteins activate early B-cell factor (Ebf1), which in turn activates expression of the B cell commitment factor, Pax5. In our studies, we use IL-7 receptor alpha chain (IL-7Rα) knockout animals that …
Genetic Complexity And Population Diversity Of Plasmodium Falciparum In The Peruvian Amazon, Patrick Lee Sutton
Genetic Complexity And Population Diversity Of Plasmodium Falciparum In The Peruvian Amazon, Patrick Lee Sutton
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GENETIC COMPLEXITY AND POPULATION DIVERSITY OF PLASMODIUM FALCIPARUM IN THE PERUVIAN AMAZON PATRICK LEE SUTTON MICROBIOLOGY GRADUATE PROGRAM ABSTRACT Characterizing the genetic complexity of immunologically relevant proteins, expressed during the life cycle of P. falciparum, is essential for identifying and advancing potential vaccine candidates. The current malaria immunity paradigm is rooted in high transmission studies which have investigated the impact of high genetic diversity on the development of humoral responses. Given the dynamic nature of malaria parasites, especially their ability to acclimate to change, it is likely that regions of low transmission do not share the same malaria immunity paradigm …
Regulation Of Tissue Remodeling Through The Calreticulin Binding Domain Of Thrombospondin-1, Mariya Ts'ana Sweetwyne
Regulation Of Tissue Remodeling Through The Calreticulin Binding Domain Of Thrombospondin-1, Mariya Ts'ana Sweetwyne
All ETDs from UAB
Thrombospondin-1 (TSP1) is a multifunctional matricellular protein released by platelets in response to injury and secreted by cells under stress. TSP1 is cleaved into functional N- and C-terminal domain fragments, which have paradoxical actions with respect to angiogenesis, cell survival, and cell adhesion. Wound healing studies by others demonstrated that TSP1 knockout mice have delayed rates of wound closure, which was attributed to actions of the C-terminal domain. We wished to investigate the specific role of the N-terminal domain in tissue remodeling. Previously, we established that a sequence (aa 17-35) in the N-terminal domain of TSP1 induces focal adhesion disassembly, …
The Role Of Gbf1 In Golgi Biogenesis And Secretory Traffic., Tomasz Szul
The Role Of Gbf1 In Golgi Biogenesis And Secretory Traffic., Tomasz Szul
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The secretory pathway within a cell consists of series of membrane compartments connected by shuttling secretory vesicles containing cargo that travel from endoplasmic reticulum (ER) though ER-to-Golgi intermediate compartment (ERGIC), the Golgi apparatus, and endosomal compartment to the plasma membrane (PM). The Golgi specific brefeldin A (BFA)-resistant factor 1 GBF1 has been identified as an important factor involved in traffic between ER and Golgi and within the Golgi apparatus. GBF1 belongs to a family of guanine nucleotide exchange factors (GEFs) that stimulate the exchange of GDP for GTP on small GTPases, ADP-ribosylation factors (ARFs). The exchange of the nucleotide activates …
The Effects Of P-Glycoprotein Deficiency On Intestinal Integrity And Homeostasis, Elizabeth Marie Staley
The Effects Of P-Glycoprotein Deficiency On Intestinal Integrity And Homeostasis, Elizabeth Marie Staley
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THE EFFECTS OF P-GLYCOPROTEIN DEFICIENCY ON INTESTINAL INTEGRITY AND HOMEOSTASIS ELIZABETH M. STALEY MICROBIOLOGY ABSTRACT P-glycoprotein (P-gp) is an ATP-binding transmembrane pump associated with substrate extrusion in cells of epithelial and hematopoietic lineage. Polymorphisms in multidrug resistance genes (MDR), which encode this protein, are associated with development of inflammatory bowel disease in patient subsets. Furthermore, FVB/N animals deficient in P-gp expression develop spontaneous colitis. Disease in FVB.mdr1a-/- animals is reported to be the result of P-gp deficiencies in intestinal epithelial cells. We developed a neonatal model of bone marrow reconstitution to accurately evaluate the contribution of P-gp deficiencies in either …
The Potential Role Of Vh Replacement In Editing And Generating Autoreactive Antibodies, Run Fan
The Potential Role Of Vh Replacement In Editing And Generating Autoreactive Antibodies, Run Fan
All ETDs from UAB
VH replacement occurs through RAG-mediated secondary recombination between an upstream VH gene and an existing VHDJH joint. In the first part of this dissertation, we focused on the potential regulation of VH replacement in the human B lineage EU12 cells muHC+ population, which underwent spontaneous VH replacement during in vitro culture. We cloned one of the dominant IgH genes, A19H, expressed in the EU12 muHC+ cells, and generated recombinant antibodies. We found that these recombinant antibodies recognize SM antigens. The anti-SM reactivity of A19H can not be efficiently neutralized by a randomly selected group of fourteen IgL chains from healthy …
Insulin Signaling And Function In Osteoblasts, Keertik S. Fulzele
Insulin Signaling And Function In Osteoblasts, Keertik S. Fulzele
All ETDs from UAB
Insulin and insulin-like growth factor-1 (IGF-1) are evolutionarily conserved hormonal signaling pathways with structurally similar ligands and receptors. Recent stu-dies suggest that that insulin and IGF-1 exert distinct as well as overlapping functions to regulate different aspects of skeletal development. A major problem in distinguishing the actions of insulin and IGF-1 is the fact that the receptors are co-expressed in many cell types and each ligand is able to cross-activate the other ligands' receptor. To distinguish direct skeletal actions of insulin from that of IGF-1, we have conditionally disrupted each receptor in vitro and in vivo specifically in osteoblasts. Studies …
Exopolysaccharides Of Mycoplasma Pulmonis, James Michael Daubenspeck
Exopolysaccharides Of Mycoplasma Pulmonis, James Michael Daubenspeck
All ETDs from UAB
Capsule has been associated with virulence in numerous bacterial pathogens. The Mollicutes are a host-specific group of pathogens that cause a variety of economically relevant diseases important to man. Mycoplasma pneumoniae is responsible for 2 million cases of atypical pneumonia and 100,000 hospitalizations every year in the United States (Atkinson et al., 2008) (Krause and Taylor-Robinson, 1992). There was a toxic galactan molecule described as early as 1958 in Mycoplasma mycoides subsp. mycoides (Plackett and Buttery, 1958), although no evidence was presented that it was produced by the bacteria. Over the intervening fifty years the evidence to support the production …
Regulation Of Redox Signaling By Lipid Electrophiles In Breast Cancer, Anne R. Diers
Regulation Of Redox Signaling By Lipid Electrophiles In Breast Cancer, Anne R. Diers
All ETDs from UAB
A number of steps in breast cancer progression and metastasis are regulated by redox signaling pathways. Electrophilic lipids such as 15-deoxy-delta12,14-Prostaglandin J2 (15d-PGJ2) are mediators of redox signaling pathways because of their ability to modify critical cysteine residues (thiols) in redox-sensitive proteins. In this thesis, we examine the effect of lipid electrophiles such as 15d-PGJ2 and others on redox signaling pathways in breast cancer. Furthermore, we develop new strategies to regulate cancer cell behavior in response to lipid electrophiles using three strategies: 1) through organelle-specific targeting of electrophiles 2) by exploiting the concentration-dependence of effects of electrophiles, and 3) utilizing …
Regulation Of Vh Replacement In Human Immature B Cells By B Cell Receptor (Bcr) - Mediated Signaling, Jing Liu
Regulation Of Vh Replacement In Human Immature B Cells By B Cell Receptor (Bcr) - Mediated Signaling, Jing Liu
All ETDs from UAB
VH replacement occurs through RAG-mediated secondary recombination to change unwanted IgH genes. In this dissertation, I focused on studying the molecular mechanism that regulates VH replacement in human immature B cells. In part I, our results show that VH replacement is regulated by B cell antigen receptor (BCR) mediated signaling. Using the human EU12 mHC+ cells as an experimental model system, crosslinking BCR with F(ab')2 anti-IgM antibodies results in BCR internalization, cell proliferation arrest, and induction of VH replacement. Pretreatment of human EU12 mHC+ cells with the protein tyrosine kinase inhibitor Genistein, Syk kinase inhibitors, and a Src kinase inhibitor …
Counterregulatory Roles Of Transforming Growth Factor (Tgf)-Beta And Atrial Natriuretic Peptide (Anp) In Pressure Overload-Induced Cardiac Remodeling And Fibrosis, Jason Anthony Lucas
Counterregulatory Roles Of Transforming Growth Factor (Tgf)-Beta And Atrial Natriuretic Peptide (Anp) In Pressure Overload-Induced Cardiac Remodeling And Fibrosis, Jason Anthony Lucas
All ETDs from UAB
Pressure overload stress (eg. hypertension or aortic stenosis) results in excessive cardiac fibrosis, changes in left ventricular (LV) geometry, and disruption of LV contractility, ultimately leading to heart failure. We hypothesize that transforming growth factor-beta (TGF-beta), a pro fibrogenic factor, and atrial natriuretic peptide (ANP), an anti fibrogenic factor, interact directly in a counterregulatory manner to balance the production of extracellular matrix (ECM) under pressure overload induced cardiac stress or hypoxia-induced pulmonary vascular adaptation. In this report, we examine structural and functional responses of the intact heart to pressure overload stress in vivo. We then utilize isolated rat pulmonary artery …
Development And Implementation Of Knock-In And Bac-In Il-2 Reporter Mouse Models To Characterize Il2 Gene Regulation In Cd4 T Cells, Rita Jeanne Luther
Development And Implementation Of Knock-In And Bac-In Il-2 Reporter Mouse Models To Characterize Il2 Gene Regulation In Cd4 T Cells, Rita Jeanne Luther
All ETDs from UAB
Maintenance of immune homeostasis involves a balance between T cell effector responses to antigen stimulus and reciprocal downregulation of this response through peripheral tolerance mechanisms. Upon exposure to pathogen, cytokine production and signaling serve to tightly coordinate cell-mediated clearance of antigen followed by contraction of the immune response. Interkeukin-2 (IL-2) is a type I family cytokine critical for expansion of activated T cells in vitro and enhancement of T cell memory responses in vivo. Deficiency of IL-2 in vivo also revealed a critical role for IL-2 in immune tolerance through the maintenance of T regulatory cell populations (Treg) in peripheral …
The Significance Of Heavy Chain Cdr3 Diversity In The Antibody Response To Polysaccharides, Tamer Mahmoud
The Significance Of Heavy Chain Cdr3 Diversity In The Antibody Response To Polysaccharides, Tamer Mahmoud
All ETDs from UAB
An understanding of the molecular mechanisms involved in the generation of protective antibody responses to polysaccharides associated with pathogenic microorganisms is of importance for improving vaccine design. The heavy chain third complementarity-determining region (HCDR3) of an antibody molecule is at the center of its antigen-binding site and plays a determinative role in antigen recognition. The goal of this dissertation was to investigate the role of HCDR3 diversity and composition on the antibody response to the polysaccharide α 1→3 Dextran (DEX). In the first study, we investigated the role of TdT, a DNA polymerase that plays a major role in generating …
Localization And Function Of Electrogenic Na/Bicarbonate Cotransporter Nbce1 In Rat Brain, Debeshi Majumdar
Localization And Function Of Electrogenic Na/Bicarbonate Cotransporter Nbce1 In Rat Brain, Debeshi Majumdar
All ETDs from UAB
Na-Coupled Bicarbonate Transporters (NCBTs) are members of the bicarbonate transporter superfamily that play important roles in regulating intracellular pH (pHi) and extracellular pH (pHo) in the central nervous system. Electrogenic Na/bicarbonate Cotransporter 1 (NBCe1) is an NCBT that is expressed in different mammalian tissues including the brain. NBCe1 has three splice variants - NBCe1-A, -B and -C - that differ in the amino and carboxy termini. We have first performed a systematic characterization of the localization profiles of the three NBCe1 splice variants at mRNA and protein levels in rat brain. In these studies, we have used anti-sense probes and …
Intracellular Trafficking Of The Hantaviral Nucleocapsid Protein And Its Function In Modulation Of Immune Signaling, Steven Joe Ontiveros
Intracellular Trafficking Of The Hantaviral Nucleocapsid Protein And Its Function In Modulation Of Immune Signaling, Steven Joe Ontiveros
All ETDs from UAB
Old World and New World hantaviruses, family Bunyaviridae, mature intracellularly within cellular compartments. Although it is generally accepted they assemble and bud in the Golgi apparatus the site remains controversial for New World hantaviruses, because some studies have raised the possibility of their maturation at the plasma membrane. Furthermore, the site of assembly hantaviruses still remains undetermined. The nucleocapsid (N) protein has been proposed to play a key role in facilitating assembly. To gain insight into the assembly pathways of Old World hantaviruses, we examine the intracellular trafficking of the Hantaan (HTN) virus N protein. We show progressive redistribution of …
A Functional Analysis Of The Human Immunodeficiency Virus, Sushma Jyotika Bhakta
A Functional Analysis Of The Human Immunodeficiency Virus, Sushma Jyotika Bhakta
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The retroviral life cycle is separated into two distinct phases of infection. In the first phase, viral enzymes and proteins allow the virus to establish infection. The virus usurps host machinery in the second stage to produce infectious virus. In both phases of the replication cycle, the envelope (Env) glycoprotein (gp) is a key component of infectivity. Env plays a pivotal role in viral entry, by mediating attachment and facilitating fusion of the viral and cellular membranes, and during assembly, where Env must be incorporated into budding virions in order to produce infectious virions. The Env cytoplasmic domain (CD) interacts …
Oxidative Stress-Stimulated Vascular Calcification, Chang Hyun Byon
Oxidative Stress-Stimulated Vascular Calcification, Chang Hyun Byon
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Oxidative stress plays a critical role in pathogenesis of atherosclerosis. However, the effect of oxidative stress-induced molecular signaling in development of vascular calcification, a feature of advanced atherosclerosis, has not been defined. Osteogenic differentiation of vascular smooth muscle cells (VSMC) is critical in development of vascular calcification. We determined hydrogen peroxide (H2O2)-induced oxidative stress promoted a phenotypic switch of mouse primary VSMC from contractile to osteogenic phenotype. This effect was associated with increased expression and transactivity of Runx2, a key transcription factor for osteogenic differentiation. Inhibition of Runx2 using short hairpin RNA blocked oxidative stress-induced VSMC calcification. By contrast, adenovirus-mediated …
Identification Of New Strategies For The Treatment Of Glioblastoma Multiforme Utilizing A Pharmacogenomic Approach: Genetic Profiles Associated With Patient Prognosis And Outcome To Capecitabine Treatment, Jessica Marie Grunda
All ETDs from UAB
Glioblastoma multiforme (GBM) is the most lethal form of primary brain neoplasm with average patient survival between 9 and 15 months even with the most aggressive treatment modalities. Unfortunately, this poor outcome has not appreciably changed in the past 50 years emphasizing the lack of traditional `trial and error' methods in identifying an efficacious treatment for GBM. Pharmacogenomics is greatly impacting cancer research through the development of personalized medicine and rationally designed treatment paradigms for the development of more efficacious and less toxic treatment modalities. The main objective of this research was to utilize a pharmacogenomic approach to identify new …
Role Of Syndecan-1 As Key Regulator Of Multiple Myeloma Pathogenesis, Yekaterina Borisovna Khotskaya
Role Of Syndecan-1 As Key Regulator Of Multiple Myeloma Pathogenesis, Yekaterina Borisovna Khotskaya
All ETDs from UAB
Syndecan-1 (CD138), a transmembrane heparan sulfate-bearing proteoglycan, is expressed at high levels on most myeloma cells and is shed into the microenvironment. In patients, high levels of serum syndecan-1 are indicative of poor prognosis and elevation of shed syndecan-1 in animal models dramatically enhances tumor growth, angiogenesis and metastasis. Because syndecan-1 is a key regulator of myeloma pathogenesis, we hypothesized that reduction of syndecan-1 levels expressed by the myeloma cells will block their growth and dissemination. Syndecan-1 knockout and knockdown variants of two human myeloma cell lines, CAG and RPMI-8226, were developed using short hairpin RNA (shRNA) technology. In vitro, …
Impact Of Genetic And Epigenetic Variability In Response To Two Test Drugs 5-Fluorouracil And Lansoprazole, Adam Michael Lee
Impact Of Genetic And Epigenetic Variability In Response To Two Test Drugs 5-Fluorouracil And Lansoprazole, Adam Michael Lee
All ETDs from UAB
Pharmacogenetics has proven to be an invaluable tool in predicting variability in drug response; however, there are numerous incidences where genetics cannot fully explain interindividual drug variability. Other factors, such as the epigenetic mechanism of DNA methylation, may offer an alternate explanation. Therefore, this dissertation focuses on both genetic and epigenetic regulation in order to gain a better understanding of the molecular basis behind drug response variability. Initial investigations focused on the antineoplastic agent 5-Fluorouracil (5-FU), which can produce severe toxicity in patients with deficiency in dihydropyrimidine dehydrogenase (DPD). Genotypic studies have identified >32 sequence variants in the DPYD gene; …
Structural And Functional Studies On Heat Shock Protein Hsp40-Hdj1 And Golgi Er Trafficking Protein Get3, Junbin Hu
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Molecular chaperones are a large group of proteins that bind and stabilize nascent polypeptides and facilitate protein folding. One major function of chaperones is to bind hydrophobic segments of nascent polypeptides to prevent them from aggregating. How chaperone Hsp40 recognizes and interacts with polypeptides and cooperates with chaperone Hsp70 is a fundamental question. The crystal structure of the putative peptide-binding fragment of Hdj1, a human member of the type II Hsp40 family was determined, suggesting the domain I of Hsp40 may possess significant flexibility which is important for Hsp40 to regulate the size of the cleft. The flexibility may be …
The Effects Of Bisphenol A (Bpa) On Erbb2-Positive Breast Cancer, Sarah Jenkins
The Effects Of Bisphenol A (Bpa) On Erbb2-Positive Breast Cancer, Sarah Jenkins
All ETDs from UAB
Bisphenol A (BPA) is a synthetically made compound used to produce a myriad of consumer goods. Recent studies have shown BPA to leach from these products in appreciable amounts, resulting in nearly ubiquitous exposure. In this study, we assessed whether chronic administration to a range of low concentrations of BPA could accelerate spontaneously developing mammary cancer using a transgenic model that over-expresses wild type ErbB2/neu transgene (MMTV-erbB2). MMTV-erbB2 mice were provided drinking water containing 0 (control), 2.5 (BPA 2.5), 25 (BPA 25), 250 (BPA 250), or 2500 (BPA 2500) µg BPA/L from eight weeks of age until sacrifice. This range …
Analysis Of The Malaria Vaccine Potential Of Plasmodium Falciparum Merozoite Surface Protein-3, Stephen James Jordan
Analysis Of The Malaria Vaccine Potential Of Plasmodium Falciparum Merozoite Surface Protein-3, Stephen James Jordan
All ETDs from UAB
Malaria causes an estimated 1-3 million deaths each year, with the majority of deaths being a result of infection with Plasmodium falciparum. No commercially available vaccine currently exists, but multiple subunit-based vaccines are in development including one based on the promising vaccine candidate P. falciparum Merozoite Surface Protein-3 (PfMSP3). PfMSP3 varies in sequence between P. falciparum isolates, but all variation is restricted to the N-terminal domain. This observation has lead to the development of a PfMSP3-based vaccine comprised solely of the highly conserved, yet poorly immunogenic, C-terminal domain. The rationale for supporting the C-terminal domain relies entirely on its conserved …
Cystic Fibrosis Transmembrane Conductance Regulator (Cftr) Modulators And Their Mechanistic Basis: Relevance To Emerging Therapies For Cystic Fibrosis, Louise Clare Pyle
Cystic Fibrosis Transmembrane Conductance Regulator (Cftr) Modulators And Their Mechanistic Basis: Relevance To Emerging Therapies For Cystic Fibrosis, Louise Clare Pyle
All ETDs from UAB
Cystic fibrosis (CF) is a lethal genetic disorder leading to pulmonary decline and premature death. The gene responsible for CF, the cystic fibrosis transmembrane conductance regulator (CFTR), serves as a chloride and bicarbonate channel situated at the apical cell surface of epithelia. The discovery of small molecules that augment channel gating of mutant CFTR (so-called `potentiators') represents a major theme of CF research, and offers hope for new therapeutic interventions. High-throughput screening (HTS) provides a means to test millions of agents in an unbiased manner for CFTR potentiating properties. New agents identified by HTS have undergone extensive pre-clinical and clinical …
Small Molecule Inhibitors Of Acid Sensing Ion Channel-1, Yawar J. Qadri
Small Molecule Inhibitors Of Acid Sensing Ion Channel-1, Yawar J. Qadri
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Acid Sensing Ion Channel 1 is one of the many proteins in the Epithelial Sodium Channel/Degenerin family. The proteins in this family interact to form cation channels with unique biophysical properties and can all be inhibited by the small molecule amiloride. Their expression in many different cell types underlies their involvement in a large variety of physiological and pathophysiological processes. ASIC-1 containing channels, specifically, are an important therapeutic target for ischemic stroke, nociception, the invasiveness of glioblastoma cells, and many other processes including anxiety and memory formation. Of the members of the ENaC/Deg family, chicken ASIC-1 is the only protein …