Reliability Issues In Imaging Genetics, 2017 Oregon Health & Science University
Reliability Issues In Imaging Genetics, Annika Eriksson
No abstract provided.
Integrative Genomic And Transcriptomic Analysis For Pinpointing Recurrent Alterations Of Plant Homeodomain Genes And Their Clinical Significance In Breast Cancer, 2016 Department of Oncology, Wayne State University School of Medicine
Integrative Genomic And Transcriptomic Analysis For Pinpointing Recurrent Alterations Of Plant Homeodomain Genes And Their Clinical Significance In Breast Cancer, Huimei Yu, Yuanyuan Jiang, Lanxin Liu, Wenqi Shan, Xiaofang Chu, Zhe Yang, Zeng-Quan Yang
Oncology Faculty Publications
A wide range of the epigenetic effectors that regulate chromatin modification, gene expression, genomic stability, and DNA repair contain structurally conserved domains called plant homeodomain (PHD) fingers. Alternations of several PHD finger-containing proteins (PHFs) due to genomic amplification, mutations, deletions, and translocations have been linked directly to various types of cancer. However, little is known about the genomic landscape and the clinical significance of PHFs in breast cancer. Hence, we performed a large-scale genomic and transcriptomic analysis of 98 PHF genes in breast cancer using TCGA and METABRIC datasets and correlated the recurrent alterations with clinicopathological features and survival of ...
A Tale Of Two Species: Evolvability, Genomic Context, And Pathogen Forecasting, 2016 University of New England
A Tale Of Two Species: Evolvability, Genomic Context, And Pathogen Forecasting, Meghan May
Biomedical Sciences Faculty Presentations
Dr. Meghan May gives an overview presentation of her research on evolution of virulence and pathogen prediction. The focus of the presentation is a group of organisms called mycoplasmas, and covered subjects include: Mycoplasma synoviae, Mycoplasma gallisepticum, genomic context, predictive modeling, sequence evolution, and genome reduction.
High-Throughput Allele-Specific Expression Across 250 Environmental Conditions, 2016 Wayne State Center for Molecular Medicine and Genetics, Wayne State University
High-Throughput Allele-Specific Expression Across 250 Environmental Conditions, Gregory A. Moyerbrailean, Allison L. Richards, Daniel Kurtz, Cynthia A. Kalita, Gordon O. Davis, Chris T. Harvey, Adnan Alazizi, Donovan Watza, Yoram Sorokin, Nancy J. Hauff, Xiang Zhou, Xiaoquan Wen, Roger Pique-Regi, Francesca Luca
Center for Molecular Medicine and Genetics
Gene-by-environment (GxE) interactions determine common disease risk factors and biomedically relevant complex traits. However, quantifying how the environment modulates genetic effects on human quantitative phenotypes presents unique challenges. Environmental covariates are complex and difficult to measure and control at the organismal level, as found in GWAS and epidemiological studies. An alternative approach focuses on the cellular environment using in vitro treatments as a proxy for the organismal environment. These cellular environments simplify the organism-level environmental exposures to provide a tractable influence on subcellular phenotypes, such as gene expression. Expression quantitative trait loci (eQTL) mapping studies identified GxE interactions in response ...
Regulation Of Polycystin-1 Function By Calmodulin Binding, 2016 University of California, Santa Barbara
Regulation Of Polycystin-1 Function By Calmodulin Binding, Nicholas Doerr, Yidi Wang, Kevin R. Kipp, Guangyi Liu, Jesse J. Benza, Vladimir Pletnev, Tengis S. Pavlov, Alexander Staruschenko, Ashraf M. Mohieldin, Maki Takahashi, Surya M. Nauli, Thomas Weimbs
Pharmacy Faculty Articles and Research
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common genetic disease that leads to progressive renal cyst growth and loss of renal function, and is caused by mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively. The PC1/PC2 complex localizes to primary cilia and can act as a flow-dependent calcium channel in addition to numerous other signaling functions. The exact functions of the polycystins, their regulation and the purpose of the PC1/PC2 channel are still poorly understood. PC1 is an integral membrane protein with a large extracytoplasmic N-terminal domain and a short, ~200 amino acid C-terminal ...
Analyzing Mutations Of Spt7 Protein That Disrupt Interaction With Sf3b Subunits, 2016 Purdue University
Analyzing Mutations Of Spt7 Protein That Disrupt Interaction With Sf3b Subunits, Arryn T. Harris, Peyton J. Spreacker, Rachel Stegeman, Vikki M. Weake, Edwin C. Acosta
The Summer Undergraduate Research Fellowship (SURF) Symposium
Proper transcription, the process of converting DNA to RNA, is crucial for the health and viability of an organism. This process is regulated by many proteins, such as co-transcriptional activators; one being the protein complex known as Spt-Ada-Gcn5-acetyltransferase, or SAGA. While much is known about the roles of SAGA in cell processes, how SAGA’s subunits promote functionality is still unknown. The focus of this study is to analyze the purpose of SAGA’s SF3B subunits. These subunits are also found in the spliceosome, the compound responsible for generating mature RNA. SAGA has no known functions relating to this process ...
Activation Of Target Gene Expression In Neurons By The C. Elegans Rfx Transcription Factor, Daf-19, 2016 Lawrence University
Activation Of Target Gene Expression In Neurons By The C. Elegans Rfx Transcription Factor, Daf-19, Katherine P. Mueller
Lawrence University Honors Projects
DAF-19, the only RFX transcription factor found in C. elegans, is required for the formation of neuronal sensory cilia. Four isoforms of the DAF-19 protein have been reported, and the m86 nonsense (null) mutation affecting all four isoforms has been shown to prevent cilia formation. Transcriptome analyses employing microarrays of L1 and adult stage worms were completed using RNA from daf-19(m86) worms and an isogenic wild type strain to identify additional putative DAF-19 target genes. Using transcriptional fusions with GFP, we compared the expression patterns of several potential gene targets using fluorescence confocal microscopy. Expression patterns were characterized in ...
Sustained Expression With Partial Correction Of Neutrophil Defects 5 Years After Intramuscular Raav1 Gene Therapy For Alpha-1 Antitrypsin Deficiency, 2016 University of Massachusetts Medical School
Sustained Expression With Partial Correction Of Neutrophil Defects 5 Years After Intramuscular Raav1 Gene Therapy For Alpha-1 Antitrypsin Deficiency, Terence R. Flotte, Christian Mueller, Gwladys Gernoux, Alisha Gruntman, Jeffrey D. Chulay, David R. Knop, Noel G. Mcelvaney, Martha Campbell-Thompson, James M. Wilson
UMass Center for Clinical and Translational Science Research Retreat
Alpha-1 antitrypsin (AAT) deficiency is a common monogenic disorder resulting in emphysema, which is currently treated with weekly infusions of protein replacement. We previously reported achieving plasma wild-type (M) AAT concentrations at 2.5-3.8% of the therapeutic level at 1 year after intramuscular (IM) administration of 6×1012vg/kg of a recombinant adeno-associated virus serotype 1 (rAAV1)-AAT vector in AAT-deficient patients, with an associated regulatory T cell (Treg) response to AAV1 capsid epitopes in the absence of any exogenous immune suppression. Here, we report sustained expression at greater than 2% of the therapeutic level for 5 years after ...
Novel Oncogenic Drivers In Pediatric Gliomagenesis, 2016 University of Tennessee Health Science Center
Novel Oncogenic Drivers In Pediatric Gliomagenesis, Alexander K. Diaz
Theses and Dissertations (ETD)
Pediatric high-grade gliomas (pHGGs), with a two-year survival rate of less than 20%, are some of the most aggressive human cancers. This dissertation begins with our analysis of 127 pHGGs, including brainstem (BS) and non-brainstem (NBS) tumors, from 118 patients using next-generation sequencing technologies. Nearly one-third of BS-HGGs, also known as diffuse intrinsic pontine gliomas (DIPGs), harbored somatic heterozygous missense mutations in ACVR1, coding for a receptor serine-threonine kinase involved in bone morphogenetic protein (BMP) signaling. These alterations led to gain-of-function as evidenced by increased phosphorylation of downstream targets in primary astrocytes and zebrafish embryo ventralization. Whole-genome sequencing and RNASeq ...
Discordant Expression Of Circulating Microrna From Cellular And Extracellular Sources, 2016 Beth Israel Deaconess Medical Center
Discordant Expression Of Circulating Microrna From Cellular And Extracellular Sources, Ravi Shah, Kahraman Tanriverdi, Daniel Levy, Martin Larson, Mark B. Gerstein, Eric O. Mick, Joel Rozowsky, Robert Kitchen, Venkatesh Murthy, Ekaterina Mikalev, Jane E. Freedman
Open Access Articles
MicroRNA (miRNA) expression has rapidly grown into one of the largest fields for disease characterization and development of clinical biomarkers. Consensus is lacking in regards to the optimal sample source or if different circulating sources are concordant. Here, using miRNA measurements from contemporaneously obtained whole blood- and plasma-derived RNA from 2391 individuals, we demonstrate that plasma and blood miRNA levels are divergent and may reflect different biological processes and disease associations.
Molecular Genetics Of Ms4a6a And Alzheimer's Disease, 2016 University of Kentucky
Molecular Genetics Of Ms4a6a And Alzheimer's Disease, Ryan Harpole
Lewis Honors College Capstone Collection
Increased Alzheimer’s disease (AD) risk has previously been associated with a SNP called rs610932 near the gene MS4A6A. The goal of this experiment was to quantify the expression of two MS4A6A isoforms in the brains of AD and non-AD subjects, particularly as a function of rs610932 genotype. According to an article titled “Alzheimer’s Disease Susceptibility Variants in the MS4A6A Gene are Associated with Altered Levels of MS4A6A Expression in Blood”, MS4A6A has four different isoforms that have been reported to be differentially expressed in the blood of AD subjects compared to non-AD subjects (Petroula et al., 2014). After ...
Pharmacogenomic Management Of Familial Hypercholesterolemia: An Integrative Review Of The Literature, 2016 University of Central Florida
Pharmacogenomic Management Of Familial Hypercholesterolemia: An Integrative Review Of The Literature, Brian V. Skibo
Honors in the Major Theses
The purpose of this thesis is to examine familial hypercholesterolemia (FH) and emerging pharmacogenomics therapies that propose to lower serum low density lipid (LDL) levels. The search of various data bases resulted in nine research articles being selected for review. Syntheses of the articles suggest emerging phamacogenomic drug therapy can improve treatment outcomes for individuals with a diagnosis of FH. The Human Genome Project (HGP) has had far reaching applications for genomic technologies and pharmacagenomic interventions, tailored to human conditions associated with select genomic traits. Synthesis of nine research articles demonstrate that little is known on the topic and reveals ...
Il-15 Mediates Mitochondrial Activity Through A Ppar𝛿-Dependent-Ppar𝛼-Independent Mechanism In Skeletal Muscle Cells, Shantaé M. Thornton, James E. Krolopp, Marcia J. Abbott
Health Sciences and Kinesiology Faculty Articles
Molecular mediators of metabolic processes, to increase energy expenditure, have become a focus for therapies of obesity. The discovery of cytokines secreted from the skeletal muscle (SKM), termed “myokines,” has garnered attention due to their positive effects on metabolic processes. Interleukin-15 (IL-15) is a myokine that has numerous positive metabolic effects and is linked to the PPAR family of mitochondrial regulators. Here, we aimed to determine the importance of PPAR𝛼 and/or PPAR𝛿 as targets of IL-15 signaling. C2C12 SKM cells were differentiated for 6 days and treated every other day with IL-15 (100 ng/mL), a PPAR𝛼 inhibitor (GW-6471 ...
Genetic Counseling Students’ Perceptions: Does Supervisory Training Affect Students’ Perceived Competence Of Their Supervisors?, Sara Malka Cohen
Post & Beyond
Clinical supervision of genetic counseling students is one of the integral methods for teaching, training and ensuring competent entry-level genetic counselors. Because of the large impact a clinical supervisor plays in his/her student’s training, the genetic counselor needs to be effective in his/her role. However, a qualified genetic counselor is not guaranteed to be a competent clinical supervisor due to the different skill set required for both counseling and supervision. Therefore, supervisor training may be a good method for aiding genetic counselors in adapting to the skills needed for successful supervision. There is a strong positive correlation ...
How The Manipulation Of The Ras Homolog Enriched In Striatum Alters The Behavioral And Molecular Progression Of Huntington’S Disease, 2015 The University of New Orleans
How The Manipulation Of The Ras Homolog Enriched In Striatum Alters The Behavioral And Molecular Progression Of Huntington’S Disease, Franklin A. Lee
University of New Orleans Theses and Dissertations
Huntington’s disease is an incurable, progressive neurological disorder characterized by loss of motor control, psychiatric dysfunction, and eventual dystonia leading to death. Despite the fact that this disorder is caused by a mutation in one single gene, there is no cure. The mutant Huntingtin (mHtt) protein is expressed ubiquitously throughout the brain but frank cell death is limited to the striatum. Recent work has suggested that Rhes, Ras homolog enriched in striatum, which is selectively expressed in the striatum, may play a role in Huntington’s disease neuropathology. In vitro studies have shown Rhes to be an E3 ligase ...
Construction And Characterization Of An Expressed Sequenced Tag Library For The Mosquito Vector Armigeres Subalbatus, 2015 University of Wisconsin–Madison
Construction And Characterization Of An Expressed Sequenced Tag Library For The Mosquito Vector Armigeres Subalbatus, George Mayhew, Lyric Bartholomay, Hang-Yen Kou, Thomas Rocheleau, Jeremy Fuchs, Matthew Aliota, I-Yu Tsao, Chiung-Yen Huang, Tze-Tze Liu, Kwang-Jen Hsiao, Shih-Feng Tsai, Ueng-Cheng Yang, Nicole Perna, Wen-Long Cho, Bruce Christensen, Cheng-Chen Chen
Lyric C. Bartholomay
Background The mosquito, Armigeres subalbatus, mounts a distinctively robust innate immune response when infected with the nematode Brugia malayi, a causative agent of lymphatic filariasis. In order to mine the transcriptome for new insight into the cascade of events that takes place in response to infection in this mosquito, 6 cDNA libraries were generated from tissues of adult female mosquitoes subjected to immune-response activation treatments that lead to well-characterized responses, and from aging, naïve mosquitoes. Expressed sequence tags (ESTs) from each library were produced, annotated, and subjected to comparative analyses. Results Six libraries were constructed and used to generate 44 ...
Functional Analysis Of Genomic Variation And Impact On Molecular And Higher Order Phenotypes, 2015 University of Tennessee Health Science Center
Functional Analysis Of Genomic Variation And Impact On Molecular And Higher Order Phenotypes, Ashutosh Kumar Pandey
Theses and Dissertations (ETD)
Reverse genetics methods, particularly the production of gene knockouts and knockins, have revolutionized the understanding of gene function. High throughput sequencing now makes it practical to exploit reverse genetics to simultaneously study functions of thousands of normal sequence variants and spontaneous mutations that segregate in intercross and backcross progeny generated by mating completely sequenced parental lines. To evaluate this new reverse genetic method we resequenced the genome of one of the oldest inbred strains of mice—DBA/2J—the father of the large family of BXD recombinant inbred strains. We analyzed ~100X wholegenome sequence data for the DBA/2J strain ...
Spleen, 2015 Emory University
Always seen as a vigorous defense organ but not a vital one, the spleen deserves a scholarship beyond its immune, blood-purifying, or iron-recycling functions. Stemmed of 261 sources, this monograph of 15 chapters and 45 illustrations presents the alpha-to-omega of an enigmatic organ, the spleen: surgical anatomy, mobility; morphology, vasculature, lymphatic drainage; innervation; innate and adaptive immune responses and neuroimmune pathways; dopamine-adrenal promiscuous expressions; nicotine-acetylcholine passages; prostaglandin synthesis; etiology, symptoms and diagnostics of the reactive and neoplastic spleen in rare congenital or systematic diseases; splenosptosis, splenomegaly and various surgical solutions; causality and treatment of the splenic rupture by non-surgical (embolization ...
Conformational Changes And Translocation Of Tissue-Transglutaminase To The Plasma Membranes: Role In Cancer Cell Migration, 2015 University of South Carolina - Columbia
Conformational Changes And Translocation Of Tissue-Transglutaminase To The Plasma Membranes: Role In Cancer Cell Migration, Ambrish Kumar, Jianjun Hu, Holly Lavoie, Kenneth Walsh, Donald Dipette, Ugra Singh
Background Tissue-transglutaminase (TG2), a dual function G-protein, plays key roles in cell differentiation and migration. In our previous studies we reported the mechanism of TG2-induced cell differentiation. In present study, we explored the mechanism of how TG2 may be involved in cell migration. Methods To study the mechanism of TG2-mediated cell migration, we used neuroblastoma cells (SH-SY5Y) which do not express TG2, neuroblastoma cells expressing exogenous TG2 (SHYTG2), and pancreatic cancer cells which express high levels of endogenous TG2. Resveratrol, a natural compound previously shown to inhibit neuroblastoma and pancreatic cancer in the animal models, was utilized to investigate the ...
Investigating The Role Of P311 In The Hypertrophic Scar, 2015 Marshall University
Investigating The Role Of P311 In The Hypertrophic Scar, Jianglin Tan, Xu Peng, Gaoxing Luo, Bing Ma, Chuan Cao, Weifeng He, Shunzong Yuan, Shirong Li, John Wilkins, Jun Wu
The mechanisms of hypertrophic scar formation are not fully understood. We previously screened the differentially expressed genes of human hypertrophic scar tissue and identified P311 gene as upregulated. As the activities of P311 in human fibroblast function are unknown, we examined the distribution of it and the effects of forced expression or silencing of expression of P311. P311 expression was detected in fibroblast-like cells from the hypertrophic scar of burn injury patients but not in peripheral blood mononuclear cells, bone marrow mesenchymal stem cells, epidermal cells or normal skin dermal cells. Transfection of fibroblasts with P311 gene stimulated the expression ...