Genetics Commons^™

C-Myc’S Role On Methylation Of The Gata-2 Gene In Non-Small Cell Lung Carcinoma, Jonathan D. Hajduk

Student Scholar Showcase

Lung cancer accounts for more deaths per year than any other form of cancer, resulting in a total of 158,000 deaths per year in the U.S. Non-small cell lung cancer (NSCLC) is diagnosed in greater than 224,000 Americans every year. Methylation and subsequent downregulation of certain genes has been directly linked to the uncontrolled growth of NSCLC cells. Natural killer (NK) cells are key innate immune cells responsible for apoptosis of cells with incorrect genetic code. It is believed that one component of uncontrolled NSCLC growth is due to the NK cells’ inability to detect errors within NSCLC cells. Perhaps …

Differential Mrna Expression In Ectopic Germinal Centers Of Myasthenia Gravis Thymus, Manjistha Sengupta, Bi-Dar Wang, Norman H. Lee, Gary Cutter, Linda L. Kusner, Henry J. Kaminski

GW Research Days 2016 - 2020

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder resulting in weakness of voluntary muscles. It is caused by antibodies directed against proteins present at the post-synaptic surface of neuromuscular junction (NMJ). A characteristic pathology of patients with early onset MG is thymic hyperplasia with ectopic germinal centers (GC). However, mechanisms that trigger and maintain thymic hyperplasia are poorly characterized.

In order to determine the central mechanisms involved in the pathology, thymus samples from MG patients were assessed by histology and grouped based on appearance of GC compared to samples without them. We assessed the differential mRNA expression profiles between the …

Crispr-Based Knockout Screening In Primary Neurons, Ben Callif

Master's Theses (2009 -)

Axon growth is coordinated by multiple interacting proteins that remain incompletely characterized. High content screening (HCS), in which manipulation of candidate genes is combined with rapid image analysis of phenotypic effects, has emerged as a powerful technique to identify key regulators of axon outgrowth. Here we explore the utility of a genome editing approach referred to as CRISPR (Clustered Regularly Interspersed Palindromic Repeats) for knockout screening in primary neurons. In the CRISPR approach a DNA-cleaving Cas enzyme is guided to genomic target sequences by user-created guide RNA (sgRNA), where it initiates a double-stranded break that ultimately results in frameshift mutation …

Hla-B*57:01 Allele Prevalence In Hiv-Infected North American Subjects And The Impact Of Allele Testing On The Incidence Of Abacavir-Associated Hypersensitivity Reaction In Hla-B*57:01-Negative Subjects, Catherine Small, D Margolis, M Shaefer, L Ross

NYMC Faculty Publications

BACKGROUND: The presence of the HLA-B*57:01 allele in HIV-infected subjects is associated with a higher risk of abacavir-associated hypersensitivity reaction (ABC HSR). HLA-B*57:01 allele prevalence varies in different populations, but HLA-B*57:01 testing with immunological confirmation has had a negative predictive value for ABC HSR between 97 and 100%. METHODS: In the ASSURE study (EPZ113734), the HLA-B*57:01 prevalence in virologically suppressed, antiretroviral treatment-experienced, HIV-infected subjects from the United States, including Puerto Rico, was assessed. RESULTS: Three hundred eighty-five subjects were screened; 13 were HLA-B*57:01 positive and 372 were negative. Only HLA-B*57:01-negative, abacavir-naive subjects were eligible to enroll into the ASSURE trial. …

Draft Genome Sequences Of Three Cellulolytic Bacillus Licheniformis Strains Isolated From Imperial Geyser, Amphitheater Springs, And Whiterock Springs Inside Yellowstone National Park, Joshua A. O'Hair, Hui Li, Santosh Thapa, Matthew Scholz, Suping Zhou

Agricultural and Environmental Sciences Faculty Research

Novel cellulolytic microorganisms are becoming more important for rapidly growing biofuel industries. This paper reports the draft genome sequences of Bacillus licheniformis strains YNP2-TSU, YNP3-TSU, and YNP5-TSU. These cellulolytic isolates were collected from several hydrothermal features inside Yellowstone National Park.

Hairy Root Transgene Expression Analysis Of A Secretory Peroxidase (Pvpox1) From Common Bean Infected By Fusarium Wilt, Renfeng Xue, Xingbo Wu, Yingjie Wang, Yan Zhuang, Jian Chen, Jing Wu, Weide Ge, Lanfen Wang, Shumin Wang, Matthew W. Blair

Agricultural and Environmental Sciences Faculty Research

Plant peroxidases (POXs) are one of the most important redox enzymes in the defense responses. However, the large number of different plant POX genes makes it necessary to carefully confirm the function of each paralogous POX gene in specific tissues and disease interactions. Fusarium wilt is a devastating disease of common bean caused by Fusarium oxysporum f. sp. phaseoli. In this study, we evaluated a peroxidase gene, PvPOX1, from a resistant common bean genotype, CAAS260205 and provided direct evidence for PvPOX1’s role in resistance by transforming the resistant allele into a susceptible common bean genotype, BRB130, via hairy root transformation …

Demethylated Hsatii Dna And Hsatii Rna Foci Sequester Prc1 And Mecp2 Into Cancer-Specific Nuclear Bodies, L. L. Hall, M. Byron, Dawn M. Carone, T. W. Whitfield, G. P. Pouliot, A. Fischer, P. Jones, J. B. Lawrence

Biology Faculty Works

This study reveals that high-copy satellite II (HSATII) sequences in the human genome can bind and impact distribution of chromatin regulatory proteins and that this goes awry in cancer. In many cancers, master regulatory proteins form two types of cancer-specific nuclear bodies, caused by locus-specific deregulation of HSATII. DNA demethylation at the 1q12 mega-satellite, common in cancer, causes PRC1 aggregation into prominent Cancer-Associated Polycomb (CAP) bodies. These loci remain silent, whereas HSATII loci with reduced PRC1 become derepressed, reflecting imbalanced distribution of UbH2A on these and other PcG-regulated loci. Large nuclear foci of HSATII RNA form and sequester copious MeCP2 …

Whole Transcriptome Comparison Between Multipotent Adult Stem Cells (Mascs) And Two Families Of Mesenchymal Stem Cells (Mscs), Jessica C. Black, Drew Cumming, Andra Sullivan, Wei-Hua Huang, Paul A. Lucas

NYMC Faculty Posters

No abstract provided.

P08. Unravelling Organelle Genome Evolution Architecture Using Rna-Sequencing Data, Matheus Sanita Lima, David Roy Smith

Western Research Forum

Background: Mitochondria genomes vary from 11 Mb to 6 kb, while plastids can vary from 1 Mb to 30 kb. Non-coding DNA accounts for most of this size variation, but the mechanistic and evolutionary reasons for that are still unknown. Next generation sequencing has generated unprecedented amounts of genomic and transcriptomic data that can be used for organelle genome evolution studies. However, most of these data is used only for the study of cell nucleus. Therefore, I decided to use these untapped data source to investigate the transcription of organelle genomes in plastid-bearing protists.

Methods: I mapped the transcriptomes over …

Molecular Regulation Of Stem Cell Behavior During Tissue Repair And Cancer Formation, Nestor J. Oviedo

Science Seminar Series

Oviedo will be presenting his work on identifying the mechanisms of adult stem cell fate determination based on their topographical location in the adult body. Understanding stem cell fate determination is crucial because tissue repair and neoplastic growth are greater in anterior than in posterior regions of adult animals. Despite its critical implications for stem cell biology, carcinogenesis and regenerative medicine, this physiological phenomenon has remained overlooked. Recent findings from his group provide intriguing evidence implying DNA repair mechanisms and cellular signaling through post-translational modifications regulate stem cell fate decision depending on their topographical location in the adult body. We …

Quantitative Limits On Small Molecule Transport Via The Electropermeome - Measuring And Modeling Single Nanosecond Perturbations, Esin B. Sözer, Zachary A. Levine, P. Thomas Vernier

Bioelectrics Publications

The detailed molecular mechanisms underlying the permeabilization of cell membranes by pulsed electric fields (electroporation) remain obscure despite decades of investigative effort. To advance beyond descriptive schematics to the development of robust, predictive models, empirical parameters in existing models must be replaced with physics- and biology-based terms anchored in experimental observations. We report here absolute values for the uptake of YO-PRO-1, a small-molecule fluorescent indicator of membrane integrity, into cells after a single electric pulse lasting only 6 ns. We correlate these measured values, based on fluorescence microphotometry of hundreds of individual cells, with a diffusion-based geometric analysis of pore-mediated …

Rapid Increase In Genetic Diversity In An Endemic Patagonian Tuco-Tuco Following A Recent Volcanic Eruption, Jeremy L. Hsu, Sharon Kam, Mauro N. Tammone, Eileen A. Lacey, Elizabeth A. Hadly

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Catastrophic natural events can have profound impacts on patterns of genetic diversity. Due to the typically unpredictable nature of such phenomena, however, few studies have been able to directly compare patterns of diversity before and after natural catastrophic events. Here, we examine the impacts of a recent volcanic eruption in southern Chile on genetic variation in the colonial tuco-tuco (Ctenomys sociabilis), a subterranean species of rodent endemic to the area most affected by the June 2011 eruption of the Puyehue-Cordón Caulle volcanic complex. To provide a comparative context for interpreting changes in genetic variation in this species, we …

Sumo Regulates The Activity Of Smoothened And Costal-2 In Drosophila Hedgehog Signaling, Jie Zhang, Yajuan Liu, Kai Jiang, Jianhang Jia

Markey Cancer Center Faculty Publications

In Hedgehog (Hh) signaling, the GPCR-family protein Smoothened (Smo) acts as a signal transducer that is regulated by phosphorylation and ubiquitination, which ultimately change the cell surface accumulation of Smo. However, it is not clear whether Smo is regulated by other post-translational modifications, such as sumoylation. Here, we demonstrate that knockdown of the small ubiquitin-related modifier (SUMO) pathway components Ubc9 (a SUMO-conjugating enzyme E2), PIAS (a SUMO-protein ligase E3), and Smt3 (the SUMO isoform in Drosophila) by RNAi prevents Smo accumulation and alters Smo activity in the wing. We further show that Hh-induced-sumoylation stabilizes Smo, whereas desumoylation by Ulp1 …

Hypoxia Inducible Factor 1: A Urinary Biomarker Of Kidney Disease., S Movafagh, Dominic Raj, M Sanaei-Ardekani, D Bhatia, K Vo, M Mahmoudieh, R Rahman, E H Kim, Arthur F Harralson

Medicine Faculty Publications

Identifying noninvasive biomarkers of kidney disease is valuable for diagnostic and therapeutic purposes. Hypoxia inducible factor 1 (HIF-1) expression is known to be elevated in the kidneys in several renal disease pathologies. We hypothesized that the urinary HIF-1a mRNA level may be a suitable biomarker for expression of this protein in chronic kidney disease (CKD). We compared HIF-1a mRNA levels from urine pellets of CKD and healthy subjects. To ensure that urinary HIF-1a mRNA is of kidney origin, we examined colocalization of HIF-1a mRNA with two kidney specific markers in urine cells. We found that HIF-1a mRNA is readily quantifiable …

The Molecular Basis Of Talin2'S High Affinity Toward Β1-Integrin, Yaxia Yuan, Liqing Li, Yanyan Zhu, Lei Qi, Latifeh Azizi, Vesa P. Hytönen, Chang-Guo Zhan, Cai Huang

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Talin interacts with β-integrin tails and actin to control integrin activation, thus regulating focal adhesion dynamics and cell migration. There are two talin genes, Tln1 and Tln2, which encode talin1 and talin2, and it is generally believed that talin2 functions redundantly with talin1. However, we show here that talin2 has a higher affinity to β1-integrin tails than talin1. Mutation of talin2 S339 to leucine, which can cause Fifth Finger Camptodactyly, a human genetic disease, completely disrupted its binding to β–integrin tails. Also, substitution of talin1 C336 with Ser enhanced the affinity of talin1, whereas substitution of talin2 S339 with …

Post-Transcriptional Regulation Of The Drosophila Anterior Determinant, Bicoid, John Mclaughlin

Dissertations, Theses, and Capstone Projects

In a wide variety of biological contexts, messenger RNA (mRNA) is known to have a complex and dynamic life cycle. In particular, the localization and translational control of mRNA are essential for proper development in eukaryotes. The fly Drosophila melanogaster is an excellent model for studying these processes. During D. melanogaster oogenesis, several mRNAs are trafficked and localized within the developing egg chamber, and regulated at the translational level to enable embryo patterning. One such mRNA, bicoid, is localized at the anterior of the oocyte and translated in the early embryo, where its encoded protein directs formation of the fly's …

Inhibition Of The Integrin/Fak Signaling Axis And C-Myc Synergistically Disrupts Ovarian Cancer Malignancy, B. Xu, Jason R. Lefringhouse, Z. Liu, D. West, Lauren A. Baldwin, C. Ou, L. Chen, Dana L. Napier, Luksana Chaiswing, Lawrence D. Brewer, Daret K. St Clair, Olivier Thibault, John R. Van Nagell, Binhua P. Zhou, R. Drapkin, J.-A. Huang, M. L. Lu, Frederick R. Ueland, X. H. Yang

Pharmacology and Nutritional Sciences Faculty Publications

Integrins, a family of heterodimeric receptors for extracellular matrix, are promising therapeutic targets for ovarian cancer, particularly high-grade serous-type (HGSOC), as they drive tumor cell attachment, migration, proliferation and survival by activating focal adhesion kinase (FAK)-dependent signaling. Owing to the potential off-target effects of FAK inhibitors, disruption of the integrin signaling axis remains to be a challenge. Here, we tackled this barrier by screening for inhibitors being functionally cooperative with small-molecule VS-6063, a phase II FAK inhibitor. From this screening, JQ1, a potent inhibitor of Myc oncogenic network, emerged as the most robust collaborator. Treatment with a combination of VS-6063 …

Association Of Body Mass Index With Dna Methylation And Gene Expression In Blood Cells And Relations To Cardiometabolic Disease: A Mendelian Randomization Approach, Michael M. Mendelson, Riccardo E. Marioni, Roby Joehanes, Chunyu Liu, Åsa K. Hedman, Stella Aslibekyan, Ellen W. Demerath, Weihua Guan, Degui Zhi, Chen Yao, Tianxiao Huan, Christine Willinger, Brian Chen, Paul Courchesne, Michael Multhaup, Marguerite R. Irvin, Ariella Cohain, Eric E. Schadt, Megan L. Grove, Jan Bressler, Kari North, Johan Sundström, Stefan Gustafsson, Sonia Shah, Allan F. Mcrae, Sarah E. Harris, Jude Gibson, Paul Redmond, Janie Corley, Lee Murphy, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background

The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain.

Methods and Findings

We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs …

Human-Nonhuman Chimeras, Ontology, And Dignity: A Constructivist Approach To The Ethics Of Conducting Research On Cross-Species Hybrids, Jonathan M. Vajda

The Hilltop Review

Developments in biological technology in the last few decades highlight the surprising and ever-expanding practical benefits of stem cells. With this progress, the possibility of combining human and nonhuman organisms is a reality, with ethical boundaries that are not readily obvious. These inter-species hybrids are of a larger class of biological entities called “chimeras.” As the concept of a human-nonhuman creature is conjured in our minds, either incredulous wonder or grotesque horror is likely to follow. This paper seeks to mitigate those worries and demotivate reasonable concerns raised against chimera research, all the while pressing current ethical positions toward their …

Predictive Screening Of M1 And M2 Macrophages Reveals The Immunomodulatory Effectiveness Of Post Spinal Cord Injury Azithromycin Treatment, John C. Gensel, Timothy J. Kopper, Bei Zhang, Michael B. Orr, William M. Bailey

Spinal Cord and Brain Injury Research Center Faculty Publications

Spinal cord injury (SCI) triggers a heterogeneous macrophage response that when experimentally polarized toward alternative forms of activation (M2 macrophages) promotes tissue and functional recovery. There are limited pharmacological therapies that can drive this reparative inflammatory state. In the current study, we used in vitrosystems to comprehensively defined markers of macrophages with known pathological (M1) and reparative (M2) properties in SCI. We then used these markers to objectively define the macrophage activation states after SCI in response to delayed azithromycin treatment. Mice were subjected to moderate-severe thoracic contusion SCI. Azithromycin or vehicle was administered beginning 30 minutes post-SCI and …