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Faculty Publications 2010, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 844 publications.

Role Of Membrane Lipids In Modulating Protein Structure & Function, Ray Supriyo

Electronic Theses and Dissertations

A-B family of toxins consists of plant toxins such as ricin and bacterial toxins such as cholera. The A subunit is the enzymatic domain and the B subunit is the receptor binding domain. Commonly, these toxins bind to the target cell plasma membrane receptors through their B subunit followed by endocytosis and a transport to the endoplasmic reticulum (ER). Inside the ER, the A subunit dissociates from the rest of the toxin, unfolds and triggers the ER quality control mechanism of ER-associated degradation (ERAD). Most ERAD substrates are purged out of the ER into the cytosol for proteasomal degradation. However, …

Discovery And Optimization Of Novel Small-Molecular Inhibitors Suppressing Stat3-Dependent Tumor Process, Xiaolei Zhang

Electronic Theses and Dissertations

With the critical role of aberrantly active Signal Transducer and Activator of Transcription (Stat) 3 protein in many human cancers, selective small-molecule inhibitors targeting the dimerization event which is required for stat3 activation, would be valuable as therapeutic agents. And the inhibitors will be useful chemical probes to clarify the complex biological functions of Stat3. By computational and structural analyses of the interaction between Stat3 and the lead dimerization disruptor, S3I-201, we have designed a diverse set of analogs. One of the most active analogs, S3I-201.1066 is derived to contain a cyclo-hexyl benzyl moiety on the amide nitrogen, which increases …

Genetically Modified Es Cells Enhance Cardiac Repair And Regeneration In The Infarcted Heart, Carley E. Glass

Electronic Theses and Dissertations

Transplanted embryonic stem (ES) cells following myocardial infarction (MI) contribute to limited cardiac repair and regeneration with improved function. Therefore novel strategies are still needed to enhance the efficacy by which ES cells differentiate into cardiac cell types and inhibit adverse remodeling in the infarcted myocardium. Our studies evaluate whether genetic manipulation of transplanted ES cells employing miR- 1, a pro-cardiac microRNA, and TIMP-1, an anti-apoptotic and anti-fibrotic protein, will enhance cardiac myocyte differentiation, inhibit native cardiac apoptosis, and reduce fibrosis in the infarcted myocardium. Furthermore, we assess levels of associated pro- (caspase-3, PTEN) and anti-(Akt) apoptotic proteins as well …

Translocation Of The Cholera Toxin A1 Subunit From The Endoplasmic Reticulum To The Cytosol, Michael Prentice Taylor

Electronic Theses and Dissertations

AB-type protein toxins such as cholera toxin (CT) consist of a catalytic A subunit and a cell-binding B subunit. CT proceeds through the secretory pathway in reverse, termed retrograde trafficking, and is delivered to the endoplasmic reticulum (ER). In order for the catalytic A1 subunit to become active it must separate from the rest of the holotoxin, and this dissociation event occurs in the ER lumen. CTA1 assumes an unfolded conformation upon dissociation from the holotoxin and is recognized by ERassociated degradation (ERAD), a quality control system that recognizes and exports misfolded proteins to the cytosol for degradation by the …

A Recombinant Myeloid-Binding Adenovirus For Targeted Pulmonary Gene Therapy, Michael O. Alberti

All ETDs from UAB

Inflammation and airway destruction are hallmarks of many debilitating lung diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), acute lung injury (ALI), and cancer. Gene-based therapeutic interventions that modulate this pathologic inflammatory response are likely to reduce the progressive destruction to lung airways. In this regard, a number of strategies have been evaluated for targeting the pul-monary vasculature; particularly those based on serotype 5 Adenovirus (Ad5). The ad-vantages of Ad over other vector systems include: in vivo stability, low oncogenic poten-tial, and large packaging capacity. Yet, specific and efficient gene delivery to the lung has been hampered …

The Effect Of Sulfasalazine On Functional Recovery And Neuropathic Pain Following Spinal Cord Injury, Kelly Dunham Atkins

All ETDs from UAB

Spinal cord injury (SCI) is a devastating condition resulting in loss of motor function as well as sensory abnormalities. Insight into the pathophysiology of SCI progression has been gained through use of pre-clinical animal models, however these have not been successful in yielding pharmacological interventions for clinical management of SCI. One proposed reason for this discrepancy may be the use of SCI models which are not fully clinically relevant and do not assess the contribution of gray matter pathology to SCI functional outcomes. Post-SCI inflammation is well-documented and may lead to downstream loss of motor function. Additionally, inflammation is thought …

Significance And Regulation Of Cd68 Expression In The Osteoclast, Jason Waid Ashley

All ETDs from UAB

The mucin-like Lysosome Associated Membrane Protein (LAMP) family member CD68 is a primarily myeloid lineage restricted transmembrane protein that is expressed in macrophages and osteoclasts. While the existence and expression pattern of human CD68 and mouse CD68 (sometimes called macrosialin) are well-known, and these molecules are routinely used as histological markers of tissue macrophages, the functional signific-ance of CD68 expression remains an unanswered question. Our overall goal is to deter-mine the significance and characterize the function of CD68 in osteoclasts and explore the effects of Receptor Activator of Nuclear Factor κB (RANK) signaling on CD68 post-translational modification. To achieve this …

Human Cytomegalovirus Ul97 Kinase Activity Modifies Cell Cycle Checkpoint Regulators, Rachel Brooke Gill

All ETDs from UAB

Human cytomegalovirus (CMV) infection results in destructive infections in neonates and immunocompromised individuals. Being the primary congenital infection in the United States, it can often result in permanent neurological deficits in infants. The current therapies for CMV infections all target the viral DNA polymerase and also have dose-limiting toxicities. Isolates resistant to ganciclovir (GCV), the therapy of choice, can sometimes overwhelm immunocompromised hosts. Better therapies for this infection are required. The CMV UL97 kinase is a key enzyme in the treatment of CMV infection because it phosphorylates GCV. Additionally, maribavir (MBV) specifically inhibits UL97 kinase activity and inhibits viral replication. …

Identification And Characterization Of Novel Adenosine Cleavage Enzymes In Mycobacteria, Kajal Buckoreelall

All ETDs from UAB

Tuberculosis (TB) is one of the leading infectious diseases in the world. An estimated one third of the world's population is infected with Mycobacterium tuberculosis, the causative pathogen of TB. With the emergence of drug resistant strains of the mycobacterium, and the HIV-TB coinfection epidemic, TB remains a global health emergency. Purine metabolism is an essential cellular component to all living cells. Previous studies have shown that differences exist between mycobacterial and human purine metabolism. One of the differences was in the metabolism of adenosine (Ado), whose cleavage was observed in mycobacterial cells whereas Ado cleavage is inefficient in human …

Pathophysiology Of Dyt1 Dystonia: Targeted Mouse Models, Chad Christopher Cheetham

All ETDs from UAB

DYT1 dystonia is an inherited movement disorder caused by a trinucleotide deletion (DeltaGAG) in the DYT1 (TOR1A) gene, which codes for the torsinA protein. Dr. Yuqing Li's laboratory previously reported the characterization of a DYT1 dystonia mouse model, a knock-in carrying DeltaGAG in Dyt1 (KI), which displays a motor learning deficit of motor skill transfer. We report here that this motor learning deficit was reversed with an anticholinergic drug, trihexyphenidyl (THP), a drug commonly used to treat movement problems in dystonia patients. We further show a potential substrate for the pathophysiology, a reduction in D2 receptors in the striatum in …

The Role Of Protein Folding And Protein Trafficking In Human Disease, Cristy Davette Tower-Gilchrist

All ETDs from UAB

This dissertation documents my findings in two unrelated projects. Project 1: Expansion of CAG repeats encoding glutamine in huntingtin and ataxin 3 causes the neurodegenerative diseases Huntington's disease (HD) and spinocerebellar ataxia 3 (SCA3), respectively. Both poly-glutamine (polyQ) expanded proteins misfold and ag-gregate within the cell. Preventing aggregation of polyQ proteins through molecular or pharmacological approaches provide therapeutic advantage in animal models of HD and SCA3. I hypothesized that the UL97 kinase encoded by the human cytomegalovirus (HCMV) may be able to prevent the aggregation of polyQ proteins. Initially, I showed that the UL97 kinase prevents the deposition of aggregates …

The Role Of Trib3 In Insulin Resistance: Its Action As Nutrient Sensor And Regulator Of Insulin Action, Jiarong Lamiquiz

All ETDs from UAB

THE ROLE OF TRIB3 IN INSULIN RESISTANCE: ITS ACTION AS NUTRIENT SENSOR AND REGULATOR OF INSULIN ACTION JIARONG LIU LAMIQUIZ PATHOLOGY ABSTRACT Insulin resistance is a hallmark of Type 2 diabetes (T2DM). A reduced capacity for insulin to stimulate increases in glucose uptake and glucose oxidation in insulin sensitive tissues, such as skeletal muscle and adipose tissue, are common defects in patients with insulin resistance, T2DM, and other related diseases. Tribbles homolog 3 (TRIB3) has been demonstrated to play a role in insulin resistance by serving as a negative regulator of Akt in mouse liver, fat, and pancreas. In a …

Erythropoiesis In The Absence Of Adult Hemoglobin, Shanrun Liu

All ETDs from UAB

The mammalian erythrocyte is a highly specialized blood cell that differentiates via an orderly series of committed progenitors in the bone marrow in a process termed erythropoiesis. During erythroid development, hemoglobin synthesis increases from early erythroid progenitors to mature enucleated red blood cells (RBCs). Although hemoglobin is the most extensively studied protein in history, the role, if any, that hemoglobin plays in erythroid development remains obscure. In this study, I ask the question what happens during erythropoiesis in the absence of hemoglobin. I demonstrate that my original hypothesis that excess free heme would accumulate in the absence of globin chain …

Analysis Of Nphp Complex Genetic Interactions Associated With Human Cilia Disorders, Svetlana Viktorovna Masyukova

All ETDs from UAB

Primary cilia are antenna-like organelles that extend from the surface of almost all mammalian cell types. They regulate many signaling pathways and sense physical and chemical changes in the extracellular environment. Defects in primary cilia cause several human disorders of different severity collectively called ciliopathies, including nephronophthisis (NPHP), Joubert syndrome (JBTS), and Meckel-Gruber syndrome (MKS). Numerous MKS, JBTS and NPHP genes have been identified but in most cases of these ciliopathies the genetic defect is unknown. Despite the fact that NPHP, JBTS and MKS patients present with distinct clinical features, they have mutations in identical genes. This can be explained …

Hemoglobin Switching, Thalassemia And Sickle Cell Disease In Humanized Knockin Mice, Sean Mcconnell

All ETDs from UAB

In this dissertation we describe knockin mouse models for the study of human hemoglobin disorders. These knockin human globin genes, in contrast to transgenes, replace the adult mouse globin genes, remain under control of endogenous mouse globin enhancer sequences and are inherited in a manner identical to globin alleles in man. Starting with various knockin alleles composed of unique human alpha, beta and gamma globin gene sequences, we evaluate several allele combinations towards our goal of generating improved models of thalassemia and sickle cells disease. We show that humanized knockin mice complete a fetal to adult hemoglobin switch during postnatal …

High Resolution Analysis Of Clonal Pluripotent Stem Cell Lentiviral Gene Therapy In A Mouse Model Of Beta-Thalassemia, Rui Yang

All ETDs from UAB

Gene therapy for hematopoietic disorders using viral vectors has achieved significant clinical benefit. However this approach has been held back by adverse genotoxic events due to random viral integration into the genome. A better understanding of viral transgene chromosomal position effects is critical for the design of safer viral vectors and clinical protocols. However, detailed analysis of viral transgenes is hampered by the heterogeneity of the viral-transduced bone marrow cell populations. I hypothesized that viral transduction of pluripotent stem cells would enable the clonal analysis of viral transgene expression, safety, and efficacy both in vitro and in vivo. Here I …

Piggybac Transposon Mutagenesis In Human And Mouse Stem Cells, Tingting Zhang

All ETDs from UAB

The most common genetic diseases worldwide, £] thalassemia and Sickle Cell Anemia (SCA) result from mutations in the adult £] globin gene. One promising therapeutic method to ameliorate these diseases is to reactivate the endogenous fetal f× globin gene. I hypothesize that an erythroid mutagenic transposon system can be used to activate f× globin gene expression. To test this hypothesis three lines of genetically modified mice were generated and bred together. The first is a transgenic mouse line that contains a multicopy array of erythroid mutagenic PiggyBac (PB) transposons. The second transgenic mouse line expresses the PB transposase (TPase) from …

Characterization Of Tbx20 Isoforms And Protein Interactions In Heart Development, Paige Debenedittis

All ETDs from UAB

Proper cardiogenesis is critical for the development of vertebrates. Abnormalities in cardiogenesis can lead to congenital heart defects (CHDs), which occur in approximately 1% of live births. The cardiac transcription factor network contains different transcription factor families which direct the expression of critical cardiac genes. Determining how the cardiac transcription factors are regulated will provide insight in the mechanisms of cardiogenesis and CHDs. The T-box (TBX) transcription factor family is an ancient gene family important for development. Several TBX genes are expressed within the developing heart and play critical roles in differentiation, proliferation, and morphogenesis. One important TBX protein is …

Ampa Receptor Trafficking In Schizophrenia, John Hammond

All ETDs from UAB

The glutamate hypothesis of schizophrenia is based primarily on NMDA receptor dysfunction. Recent studies have led to an expansion of this hypothesis to include AMPA receptors which are essential for neurotransmission through NMDA receptors. Examination of total AMPA receptor protein expression in schizophrenia has been inconsistent and led to examination of AMPA receptor interacting proteins and trafficking and subcellular localization of the receptors. AMPA receptors are highly trafficked from the endoplasmic reticulum to the synapse and in a complex system of endosomes. Alterations in the subcellular localization of these receptors may be a part of the underlying pathophysiology of schizophrenia. …

Bone Morphogenetic Protein Signaling Pathways During Mouse Heart Development: Roles For Chd7 And Mycn, Cristina Harmelink

All ETDs from UAB

Bone Morphogenetic Protein (BMP) signaling pathways are imperative for proper heart development. BMP ligands bind serine threonine kinase receptors, which activate intracellular receptor-regulated SMAD proteins. SMAD1, SMAD5, and SMAD8 transduce BMP signals from the cytoplasm to the nucleus, where they regulate transcription. We have investigated two aspects of BMP signaling during mouse cardiogenesis: identifying SMAD1-interacting proteins and exploring the roles of a known BMP target, Mycn, in the developing myocardium. Chromodomain helicase DNA binding protein 7 (CHD7) is a highly conserved transcription factor that promotes protein synthesis, proliferation, and differentiation. Haploinsufficiency for CHD7 causes CHARGE syndrome, a developmental disorder characterized …

Protein Kinase C Δ Is Critical For Nucleotide Excision Repair Of Cyclobutane Pyrimidine Dimers, Christopher Michael Negro

Master's Theses

Nucleotide excision repair (NER) is the process by which cells identify and repair bulky, helix-distorting DNA lesions such as ultraviolet (UV) radiation-induced cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PP). NER in human cells is a complex biochemical process requiring several complementation groups. Defects in complementation group genes result in rare, autosomal recessive cancer syndromes such as xeroderma pigmentosum (XP), cockayne syndrome (CS), and trichothiodystrophy, supporting the tumor suppressive effects of NER. Protein Kinase C delta (PKCδ) expression is lost in squamous cell carcinomas where it functions as a tumor suppressor gene. Additionally, in response to UV radiation, PKCδ is …

P16 Ink4a Immunocytochemistry On Cell Blocks As An Adjunct To Cervical Cytology: Potential Reflex Testing On Specially Prepared Cell Blocks From Residual Liquid-Based Cytology Specimens, Vinod B. Shidham, Ravi Mehrotra, George Varsegi, Krista L. D'Amore, Bryan Hunt, Raj Narayan

Department of Pathology

Background: p16 INK4a (p16) is a well-recognized surrogate molecular marker for human papilloma virus (HPV) related squamous dysplasia. Our hypothesis is that the invasive interventions and related morbidities could be avoided by objective stratification of positive cytologic interpretations by p16 immunostaining of cell block sections of cytology specimens.

Materials and Methods: Nuclear immunoreactivity for p16 was evaluated in cell block sections in 133 adequate cases [20 negative for intraepithelial lesion or malignancy, 28 high-grade squamous intraepithelial lesion (HSIL), 50 low-grade squamous intraepithelial lesion (LSIL), 21 atypical squamous cells, cannot exclude HSIL (ASC-H), and 14 atypical squamous cells of undetermined significance …

Regional Expression Of Hoxa4 Along The Aorta And Its Potential Role In Human Abdominal Aortic Aneurysms, John H. Lillvis, Robert Erdman, Charles M. Schworer, Alicia Golden, Kimberly Derr, Zoran Gatalica, Laura A. Cox, Jianbin Shen, Richard S. Vander Heide, Guy M. Lenk, Leigh Hlavaty, Li Li, James R. Elmore, David P. Franklin, John L. Gray, Robert P. Garvin, David J. Carey, Wayne D. Lancaster, Gerard Tromp, Helena Kuivaniemi

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The infrarenal abdominal aorta exhibits increased disease susceptibility relative to other aortic regions. Allograft studies exchanging thoracic and abdominal segments showed that regional susceptibility is maintained regardless of location, suggesting substantial roles for embryological origin, tissue composition and site-specific gene expression.

Results

We analyzed gene expression with microarrays in baboon aortas, and found that members of the HOX gene family exhibited spatial expression differences. HOXA4 was chosen for further study, since it had decreased expression in the abdominal compared to the thoracic aorta. Western blot analysis from 24 human aortas demonstrated significantly higher HOXA4 protein levels in thoracic …

The Effect Of Various Carbohydrate Supplements On Postprandial Blood Glucose Response In Female Soccer Players, Nina Pannoni

USF Tampa Graduate Theses and Dissertations

PURPOSE: The purpose of this study is to examine the effects of different types of carbohydrates on blood glucose response in collegiate soccer athletes at rest. This will help to determine the effectiveness of a carbohydrate supplement in providing sustained energy and maintained performance if ingested prior to a soccer match. METHODS: In a cross-over design, 10 female collegiate soccer players (n= 10, age 20.10 ± .99 years, height 65.55 ± 2.77 inches, weight 64.12 ± 8.36 kilograms) from the University of South Florida reported to the laboratory on five separate occasions after an overnight fast. Once a baseline blood …

From The Home To The Hospital: The New Bath Salts, Jeanne Zukas Do, Matthew D. Cook Do

Department of Medicine

No abstract provided.

The Effect Of High Dose Total Body Irradiation On Acth, Corticosterone, And Catecholamines In The Rat, Eric P. Cohen, Eric D. Bruder, William E. Cullinan, Dana R. Ziegler, Hershel Raff

Biomedical Sciences Faculty Research and Publications

Total body irradiation (TBI) or partial body irradiation is a distinct risk of accidental, wartime, or terrorist events. Total body irradiation is also used as conditioning therapy before hematopoietic stem cell transplantation. This therapy can result in injury to multiple tissues and might result in death as a result of multiorgan failure. The hypothalamic–pituitary–adrenal (HPA) axis could play a causative role in those injuries, in addition to being activated under conditions of stress. In a rat model of TBI, we have established that radiation nephropathy is a significant lethal complication, which is caused by hypertension and uremia. The current study …

Differential Effects Of Isoflurane And Propofol Anesthesia On Neurogenesis In Young And Aged Rats, Diana Marcela Erasso

USF Tampa Graduate Theses and Dissertations

Worldwide, millions of young and elderly patients receive procedures that could not be performed without the use of anesthetics. Unfortunately, emerging animal and human data suggest an association between exposure to general anesthesia and impairment of cognitive function in pediatric and geriatric patients. Recent laboratory data have shown that general anesthetics are potentially damaging to the developing and aging brain. However, the mechanism by which this happens is still unknown. General anesthetics affect learning and memory, a brain function involving neural plasticity. An important form of neural plasticity receiving attention is postnatal neurogenesis. This process is highly regulated and involved …

Acquired Cytogenetic Changes In Adult Twins Discordant For A History Of Childhood Sexual Abuse, Jenni Brumelle

Theses and Dissertations

The primary study aim was to evaluate the latent biological effect of childhood sexual abuse (CSA) on adults by quantifying acquired cytogenetic changes and cortisol levels in identical twins who were discordant (N=22) or concordant (N=2) for a history of CSA. Although the difference scores for cortisol values between discordant identical co-twins were not significantly different from zero, a trend was observed for the twins exposed to intercourse, the most severe form of CSA, to have a blunted cortisol awakening response. Acquired cytogenetic changes were assessed by scoring telomere lengths and somatic cell abnormality frequencies via a cytokinesis-block micronucleus (MN) …

Genome-Wide Association Studies At The Interface Of Alzheimer’S Disease And Epidemiologically Related Disorders, Christopher Ryan Simmons

University of Kentucky Doctoral Dissertations

Genome-wide association studies (GWAS)s provide an unbiased means of exploring the landscape of complex genetic disease. As such, these studies have identified genetic variants that are robustly associated with a multitude of conditions. I hypothesize that these genetic variants serve as excellent tools for evaluation of the genetic interface between epidemiologically related conditions. Herein, I test the association between SNPs associated with either (i) plasma lipids, (ii) rheumatoid arthritis (RA) or (iii) diabetes mellitus (DM) and late-onset Alzheimer’s disease (AD) to identify shared genetic variants. Regarding the most significantly AD-associated variants, I have also attempted to elucidate their molecular function. …