Genetics and Genomics Commons^™

A Human Papillomavirus-Independent Cervical Cancer Animal Model Reveals Unconventional Mechanisms Of Cervical Carcinogenesis, Chunbo He, Xiangmin Lv, Cong Huang, Peter C. Angeletti, Guohua Hua, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bowen Ma, Xingcheng Chen, Paul F. Lambert, Bo R. Rueda, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

HPV infections are common in healthy women and only rarely cause cervical cancer, suggesting that individual genetic susceptibility may play a critical role in the establishment of persistent HPV infection and the development of cervical cancer. Here, we provide convincing in vitro and in vivo evidence showing that differential expression and activation of YAP1 oncogene determine individual susceptibility to HPV infection and cervical carcinogenesis. We found that hyperactivation of YAP1 in mouse cervical epithelium was sufficient to induce invasive cervical cancer. Cervical epithelial cell-specific HPV16 E6/E7 and YAP1 double-knockin mouse model demonstrated that high-risk HPV synergized with hyperactivated YAP1 to …

Longer Trinucleotide Repeats Of Androgen Receptor Gene: Infertility In Males, Mussarat Ashraf, Hemaila Tariq, Rehana Rehman

Department of Biological & Biomedical Sciences

No abstract provided.

Yap1-Lats2 Feedback Loop Dictates Senescent Or Malignant Cell Fate To Maintain Tissue Homeostasis, Chunbo He, Xiangmin Lv, Cong Huang, Guohua Hua, Bowen Ma, Xingcheng Chen, Peter C. Angeletti, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bo R. Rueda, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

Dysfunction of the homeostasis-maintaining systems in specific cell types or tissues renders the organism susceptible to a range of diseases, including cancers. One of the emerging mechanisms for maintaining tissue homeostasis is cellular senescence. Here, we report that the Hippo pathway plays a critical role in controlling the fate of ovarian cells. Hyperactivation of Yes-associated protein 1 (YAP1), the major effector of the Hippo pathway, induces senescence in cultured primary human ovarian surface epithelial cells (hOSEs). Large tumor suppressor 2 (LATS2), the primary upstream negative regulator of YAP1, is elevated in both YAP1-induced and natural replicative-triggered senescence. Deletion of LATS2 …

Cyclin C: The Story Of A Non-Cycling Cyclin, Jan Jezek, Daniel G J Smethurst, David C Stieg, Z A C Kiss, Sara E Hanley, Vidyaramanan Ganesan, Kai-Ti Chang, Katrina F Cooper, Randy Strich

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The class I cyclin family is a well-studied group of structurally conserved proteins that interact with their associated cyclin-dependent kinases (Cdks) to regulate different stages of cell cycle progression depending on their oscillating expression levels. However, the role of class II cyclins, which primarily act as transcription factors and whose expression remains constant throughout the cell cycle, is less well understood. As a classic example of a transcriptional cyclin, cyclin C forms a regulatory sub-complex with its partner kinase Cdk8 and two accessory subunits Med12 and Med13 called the Cdk8-dependent kinase module (CKM). The CKM reversibly associates with the multi-subunit …

Design And Characterization Of A Consensus Hemagglutinin Vaccine Immunogen Against H3 Influenza A Viruses Of Swine, Haiyan Sun, Jung-Hyang Sur, Sarah Vitosh-Sillman, David J. Steffen, Hiep Vu

Nebraska Center for Virology: Faculty Publications

The substantial genetic diversity exhibited by influenza A viruses of swine (IAV-S) represents the main challenge for the development of a broadly protective vaccine against this important pathogen. The consensus vaccine immunogen has proven an effective vaccinology approach to overcome the extraordinary genetic diversity of RNA viruses. In this project, we sought to determine if a consensus IAV-S hemagglutinin (HA) immunogen would elicit broadly protective immunity in pigs. To address this question, a consensus HA gene (designated H3-CON.1) was generated from a set of 1,112 H3 sequences of IAV-S recorded in GenBank from 2011 to 2015. The consensus HA gene …

Overview Of Direct Thrombin Inhibitors For Use In Staphylococcus Aereus Infections, Joseph C. Risler

Honors Undergraduate Theses

The pathogenicity and intractable nature of the microorganism Staphylococcus aureus (SA) has been long documented and highlighted by many health care agencies, with emphasis on its ability to exploit the human coagulation system to deadly effect. Two drugs from a class of inhibitors known as Direct Thrombin Inhibitors (DTI) have been shown to have a substantial effect on the enzyme secreted by SA known as Staphylocoagulase (SC), but up until now the application of this potential treatment has been limited. This paper strives to supply an overview of these clinical studies and propose a novel protocol for testing DTI's on …

Mechanisms Of Trinucleotide Repeat Instability During Dna Synthesis, Kara Y. Chan

Theses and Dissertations--Toxicology and Cancer Biology

Genomic instability, in the form of gene mutations, insertions/deletions, and gene amplifications, is one of the hallmarks in many types of cancers and other inheritable genetic disorders. Trinucleotide repeat (TNR) disorders, such as Huntington’s disease (HD) and Myotonic dystrophy (DM) can be inherited and repeats may be extended through subsequent generations. However, it is not clear how the CAG repeats expand through generations in HD. Two possible repeat expansion mechanisms include: 1) polymerase mediated repeat extension; 2) persistent TNR hairpin structure formation persisting in the genome resulting in expansion after subsequent cell division. Recent in vitro studies suggested that a …

A Poxvirus Pseudokinase Represses Viral Dna Replication Via A Pathway Antagonized By Its Paralog Kinase, Annabel T. Olson, Zhigang Wang, Amber B. Rico, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Poxviruses employ sophisticated, but incompletely understood, signaling pathways that engage cellular defense mechanisms and simultaneously ensure viral factors are modulated properly. For example, the vaccinia B1 protein kinase plays a vital role in inactivating the cellular antiviral factor BAF, and likely orchestrates other pathways as well. In this study, we utilized experimental evolution of a B1 deletion virus to perform an unbiased search for suppressor mutations and identify novel pathways involving B1. After several passages of the ΔB1 virus we observed a robust increase in viral titer of the adapted virus. Interestingly, our characterization of the adapted viruses reveals that …

Persistent Viral Reservoirs In Lymphoid Tissues In Siv-Infected Rhesus Macaques Of Chinese-Origin On Suppressive Antiretroviral Therapy, Summer Siddiqui, Stefanie Perez, Yong Gao, Lara Doyle-Meyers, Brian T. Foley, Qingsheng Li, Binhua Ling

Nebraska Center for Virology: Faculty Publications

Understanding HIV latent reservoirs in tissues is essential for the development of new strategies targeting these sites for eradication. Here, we assessed the size of latent reservoirs and the source of residual viruses in multiple lymphoid tissues of SIV-infected and fully suppressed rhesus macaques of Chinese-origin (cRMs). Eight cRMs were infected with SIVmac251 and treated with tenofovir and emtricitabine daily for 24 weeks initiated 4 weeks post-infection. Four of the eight animals reached sustained full viral suppression with undetectable viremia. The levels of cell-associated SIV DNA varied in peripheral blood mononuclear cells (PBMCs) and multiple lymphoid tissues, but with higher …

Relationship Between The Cervical Microbiome, Hiv Status, And Precancerous Lesions, Cameron Klein, Daniela Gonzalez, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, Nirosh Aluthge, Samodha Fernando, John T. West, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Nearly all cervical cancers are causally associated with human papillomavirus (HPV). The burden of HPV-associated dysplasias in sub-Saharan Africa is influenced by HIV. To investigate the role of the bacterial microbiome in cervical dysplasia, cytobrush samples were collected directly from cervical lesions of 144 Tanzanian women. The V4 hypervariable region of the 16S rRNA gene was amplified and deep sequenced. Alpha diversity metrics (Chao1, PD whole tree, and operational taxonomic unit [OTU] estimates) displayed significantly higher bacterial richness in HIV-positive patients (P = 0.01) than in HIV-negative patients. In HIV-positive patients, there was higher bacterial richness in patients with …

Near-Atomic Structure Of A Giant Virus, Qianglin Fang, Dongjie Zhu, Irina Agarkova, Jagat Adhikari, Thomas Klose, Yue Liu, Zhenguo Chen, Yingyuan Sun, Michael L. Gross, James L. Van Etten, Xinzheng Zhang, Michael G. Rossmann

Nebraska Center for Virology: Faculty Publications

Although the nucleocytoplasmic large DNA viruses (NCLDVs) are one of the largest group of viruses that infect many eukaryotic hosts, the near-atomic resolution structures of these viruses have remained unknown. Here we describe a 3.5 Å resolution icosahedrally averaged capsid structure of Paramecium bursaria chlorella virus 1 (PBCV-1). This structure consists of 5040 copies of the major capsid protein, 60 copies of the penton protein and 1800 minor capsid proteins of which there are 13 different types. The minor capsid proteins form a hexagonal network below the outer capsid shell, stabilizing the capsid by binding neighboring capsomers together. The size …

A Single-Cycle Adenovirus Type 7 Vaccine For Prevention Of Acute Respiratory Disease, Brianna L. Bullard, Brigette N. Corder, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Adenovirus type 7 (Ad7) infection is associated with acute respiratory disease (ARD), especially in military recruits living in close quarters. Recently, several outbreaks of Ad7 infections have occurred in civilian populations, with some cases leading to death. However, the current Ad7 vaccine is licensed for use only in military recruits because it utilizes an orally delivered wild type virus which is shed in the stool for 28 days after immunization. This poses a safety risk due to the possibility of virus spread to vulnerable populations. To address the need for a safer Ad7 vaccine for use in civilian populations, we …

A Double Humanized Blt-Mice Model Featuring A Stable Human-Like Gut Microbiome And Human Immune System, Lance Daharsh, Jianshui Zhang, Amanda E. Ramer-Tait, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

Humanized mice (hu-mice) that feature a functional human immune system have fundamentally changed the study of human pathogens and disease. They can be used to model diseases that are otherwise difficult or impossible to study in humans or other animal models. The gut microbiome can have a profound impact on human health and disease. However, the murine gut microbiome is very different than the one found in humans. There is a need for improved pre-clinical hu-mice models that have an engrafted human gut microbiome. Therefore, we created double hu-mice that feature both a human immune system and stable human-like gut …

The Vaccinia Virus (Vacv) B1 And Cellular Vrk2 Kinases Promote Vacv Replication Factory Formation Through Phosphorylation-Dependent Inhibition Of Vacv B12, Annabel T. Olson, Zhigang Wang, Annabel Olson, Alexandria C. Linville, Brianna L. Bullard, Eric A. Weaver, Clinton Jones, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Comparative examination of viral and host protein homologs reveals novel mechanisms governing downstream signaling effectors of both cellular and vi- ral origin. The vaccinia virus B1 protein kinase is involved in promoting multiple facets of the virus life cycle and is a homolog of three conserved cellular enzymes called vaccinia virus-related kinases (VRKs). Recent evidence indicates that B1 and VRK2 mediate a com- mon pathway that is largely uncharacterized but appears independent of previous VRK substrates. Interestingly, separate studies described a novel role for B1 in inhibiting vac- cinia virus protein B12, which otherwise impedes an early event in the …

Efficacy Of A T Cell-Biased Adenovirus Vector As A Zika Virus Vaccine, Brianna L. Bullard, Brigette N. Corder, Matthew J. Gorman, Michael S. Diamond, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV) is a major public health concern due to the risk of congenital Zika syndrome in developing fetuses and Guillain-Barre syndrome in adults. Currently, there are no approved vaccines available to protect against infection. Adenoviruses are safe and highly immunogenic vaccine vectors capable of inducing lasting humoral and cellular immune responses. Here, we developed two Adenovirus (Ad) vectored Zika virus vaccines by inserting a ZIKV prM-E gene expression cassette into human Ad types 4 (Ad4-prM-E) and 5 (Ad5-prM-E). Immune correlates indicate that Ad5-prM-E vaccination induces both an anti-ZIKV antibody and T-cell responses whereas Ad4-prM-E vaccination only induces a …

Als Mutations Of Fus Suppress Protein Translation And Disrupt The Regulation Of Nonsense-Mediated Decay, Marisa Kamelgarn, Jing Chen, Lisha Kuang, Huan Jin, Edward J. Kasarskis, Haining Zhu

Toxicology and Cancer Biology Faculty Publications

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by preferential motor neuron death. Approximately 15% of ALS cases are familial, and mutations in the fused in sarcoma (FUS) gene contribute to a subset of familial ALS cases. FUS is a multifunctional protein participating in many RNA metabolism pathways. ALS-linked mutations cause a liquid–liquid phase separation of FUS protein in vitro, inducing the formation of cytoplasmic granules and inclusions. However, it remains elusive what other proteins are sequestered into the inclusions and how such a process leads to neuronal dysfunction and degeneration. In this study, we developed …

Dna Methylation By Restriction Modification Systems Affects The Global Transcriptome Profile In Borrelia Burgdorferi, Timothey Casselli, Yvonne Tourand, Adam Scheidegger, William K. Arnold, Anna Proulx, Brian Stevenson, Catherine A. Brissette

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Prokaryote restriction modification (RM) systems serve to protect bacteria from potentially detrimental foreign DNA. Recent evidence suggests that DNA methylation by the methyltransferase (MTase) components of RM systems can also have effects on transcriptome profiles. The type strain of the causative agent of Lyme disease, Borrelia burgdorferi B31, possesses two RM systems with N6-methyladenosine (m6A) MTase activity, which are encoded by the bbe02 gene located on linear plasmid lp25 and bbq67 on lp56. The specific recognition and/or methylation sequences had not been identified for either of these B. burgdorferi MTases, and it was not previously known whether these RM …

Floxed-Cassette Allelic Exchange Mutagenesis Enables Markerless Gene Deletion In Chlamydia Trachomatis And Can Reverse Cassette-Induced Polar Effects, Gabrielle Keb, Robert Hayman, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

As obligate intracellular bacteria, Chlamydia spp. have evolved numerous, likely intricate, mechanisms to create and maintain a privileged intracellular niche. Recent progress in elucidating and characterizing these processes has been bolstered by the development of techniques enabling basic genetic tractability. Florescence-reported allelic exchange mutagenesis (FRAEM) couples chromosomal gene deletion with the insertion of a selection cassette encoding antibiotic resistance and green fluorescent protein (GFP). Similar to other bacteria, many chlamydial genes exist within polycistronic operons, raising the possibility of polar effects mediated by insertion cassettes. Indeed, FRAEM-mediated deletion of Chlamydia trachomatis tmeA negatively impacts the expression of tmeB. We …

Kaposi’S Sarcoma-Associated Herpesvirus Seropositivity Is Associated With Type 2 Diabetes Mellitus: A Case–Control Study In Xinjiang, China, Meng Cui, Qiwen Fang, Jun Zheng, Zhanjun Shu, Yin Chen, Yage Fan, Juan Zhao, Charles Wood, Tiejun Zhang, Yan Zeng

Nebraska Center for Virology: Faculty Publications

Objective: To assess the potential relationship between Kaposi’s sarcoma-associated herpesvirus (KSHV) infection and type 2 diabetes mellitus (DM-2) in Xinjiang, China.

Methods: A case–control study of consecutively included DM-2 patients and normal controls was conducted among the Uygur and Han populations in Xinjiang Uygur Autonomous Region, China. Blood samples were collected and KSHV seroprevalence, antibody titers, and viral load were investigated. Logistic regression analysis and multiple linear regression analysis were applied to explore determinants of the main outcome measures.

Results: A total of 324 patients with DM-2 and 376 normal controls were included. The seroprevalence of KSHV was 49.1% (95% …

Gene Gangs Of The Chloroviruses: Conserved Clusters Of Collinear Monocistronic Genes, Phillip Seitzer, Adrien Jeanniard, Fangrui Ma, James L. Van Etten, Marc T. Facciotti, David D. Dunigan

Nebraska Center for Virology: Faculty Publications

Chloroviruses (family Phycodnaviridae) are dsDNA viruses found throughout the world’s inland waters. The open reading frames in the genomes of 41 sequenced chloroviruses (330 + 40 kbp each) representing three virus types were analyzed for evidence of evolutionarily conserved local genomic “contexts”, the organization of biological information into units of a scale larger than a gene. Despite a general loss of synteny between virus types, we informatically detected a highly conserved genomic context defined by groups of three or more genes that we have termed “gene gangs”. Unlike previously described local genomic contexts, the definition of gene gangs requires only …

Antibody Epitope Specificity For Dsdna Phosphate Backbone Is An Intrinsic Property Of The Heavy Chain Variable Germline Gene Segment Used, Tatjana Srdic-Rajic, Heinz Kohler, Vladimir Jurisic, Radmila Metlas

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Analysis of protein sequences by the informational spectrum method (ISM) enables characterization of their specificity according to encoded information represented with defined frequency (F). Our previous data showed that F(0.367) is characteristic for variable heavy chain (VH) domains (a combination of variable (V), diversity (D) and joining (J) gene segments) of the anti-phosphocholine (PC) T15 antibodies and mostly dependent on the CDR2 region, a site for PC phosphate group binding. Because the T15 dsDNA-reactive U4 mutant also encodes F(0.367), we hypothesized that the same frequency may also be characteristic for anti-DNA antibodies. Data obtained from an analysis of 60 spontaneously …

Identification Of Chst9 As A Candidate Gene For Schizophrenia From Whole Genome Sequencing, Christopher Sharp, Jingchun Chen, Marvi Moreno, Mahtab Hamid, Francisco Servin, Bita Bashy, Travis Mize

LSAMP Poster Presentations

Recent results imply that rare variants contribute to the risk of schizophrenia. We conducted whole genome sequencing for 99 subjects from 20 Chinese families (parents and at least two siblings with a schizophrenia diagnosis and one unaffected sibling). Of the 9 frameshift mutations identified in more than 2 families, one was at chromosome 10:125780762 on the Carbohydrate Sulfotransferase 15 (CHST15) gene and another at chromosome 18:24722723 on the Carbohydrate Sulfotransferase 9 (CHST9) gene. We observed these deletions in 4 affected persons of two families from whole. At least two types of mutations (one or three bases insertion) have been identified …

Susceptibility Genes To Plant Viruses, Hernan Garcia-Ruiz

Nebraska Center for Virology: Faculty Publications

Plant viruses use cellular factors and resources to replicate and move. Plants respond to viral infection by several mechanisms, including innate immunity, autophagy, and gene silencing, that viruses must evade or suppress. Thus, the establishment of infection is genetically determined by the availability of host factors necessary for virus replication and movement and by the balance between plant defense and viral suppression of defense responses. Host factors may have antiviral or proviral activities. Proviral factors condition susceptibility to viruses by participating in processes essential to the virus. Here, we review current advances in the identification and characterization of host factors …

Transcriptomic Insights On The Virulence-Controlling Csra, Badr, Rpon, And Rpos Regulatory Networks In The Lyme Disease Spirochete, William K. Arnold, Christina R. Savage, Kathryn G. Lethbridge, Trever C. Smith, Catherine A. Brisette, Janakiram Seshu, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi, the causative agent of Lyme disease, survives in nature through a cycle that alternates between ticks and vertebrates. To facilitate this defined lifestyle, B. burgdorferi has evolved a gene regulatory network that ensures transmission between those hosts, along with specific adaptations to niches within each host. Several regulatory proteins are known to be essential for the bacterium to complete these critical tasks, but interactions between regulators had not previously been investigated in detail, due to experimental uses of different strain backgrounds and growth conditions. To address that deficit in knowledge, the transcriptomic impacts of four critical …

N-Terminal Domain Of Human Uracil Dna Glycosylase (Hung2) Promotes Targeting To Uracil Sites Adjacent To Ssdna-Dsdna Junctions, Brian P Weiser, Gaddiel Rodriguez, Philip A Cole, James T Stivers

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The N-terminal domain (NTD) of nuclear human uracil DNA glycosylase (hUNG2) assists in targeting hUNG2 to replication forks through specific interactions with replication protein A (RPA). Here, we explored hUNG2 activity in the presence and absence of RPA using substrates with ssDNA-dsDNA junctions that mimic structural features of the replication fork and transcriptional R-loops. We find that when RPA is tightly bound to the ssDNA overhang of junction DNA substrates, base excision by hUNG2 is strongly biased toward uracils located 21 bp or less from the ssDNA-dsDNA junction. In the absence of RPA, hUNG2 still showed an 8-fold excision bias …

Inhibition Of Ribosome Biogenesis Through Genetic And Chemical Approaches, Leonid Anikin

Graduate School of Biomedical Sciences Theses and Dissertations

In order to maintain the ability to generate proteins, proliferating cells must continuously generate ribosomes, designating up to 80% of their energy to ribosome biogenesis (RBG). RBG involves transcription of rDNA by RNA polymerases I (Pol I) and III (Pol III), expression of approximately 80 ribosomal proteins, and assembly of these components in a process referred to as ribosome maturation. During maturation, the Pol I transcribed 47S pre-rRNA undergoes a number of processing events, while simultaneously interacting with processing factors and ribosomal proteins that drive pre-ribosome assembly. Inhibition of RBG has become one of the pursued targets for cancer therapy …

Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor

Electronic Theses and Dissertations

Metabolomics, the study of small molecules in biological systems, has enjoyed great success in enabling researchers to examine disease-associated metabolic dysregulation and has been utilized for the discovery biomarkers of disease and phenotypic states. In spite of recent technological advances in the analytical platforms utilized in metabolomics and the proliferation of tools for the analysis of metabolomics data, significant challenges in metabolomics data analyses remain. In this dissertation, we present three of these challenges and Bayesian methodological solutions for each. In the first part we develop a new methodology to serve a basis for making higher order inferences in metabolomics, …

Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle

Electronic Theses and Dissertations

Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences …

Rna-Seq Reveals Transcriptomic Program Associated With Stemness In Taxane Resistant Prostate Cancer, Christina K. Cajigas-Du Ross

Loma Linda University Electronic Theses, Dissertations & Projects

There is no cure for advanced prostate cancer (PCa), and taxane chemotherapy is the only treatment option once other therapies have failed. However, this is problematic since all patients eventually develop chemoresistance. Emerging treatments for advanced PCa have shown promise at the benchside, but clinical trials have not resulted in newly approved drugs due in part to redundant survival pathways utilized by prostate tumor cells to maintain therapy-resistance. Using RNAsequencing—an innovative approach for quantifying gene expression changes—this dissertation sought to elucidate chemoresistance-associated molecular pathways as a catalyst to develop new therapeutic targets. Results revealed a differential upregulation of stemness-associated genes …

Identifying Kif Subtype That Mediates Axonal Targeting Of Kv7 Channels, Allison Houghton, Jennifer Walters, Mary Hong, Dhruv Joshi, Hee Jung Chung

PRECS 2018

Early-onset Benign Familial Neonatal Epilepsy (BFNE) and Epileptic Encephalopathy (EE), are associated with mutations in neuronal KCNQ/Kv7 channel subunits Kv7.2 and Kv7.3. Kv7 channels are voltage-dependent potassium channels. Enriched at the axonal plasma membrane, they pump potassium ions out of the neurons and inhibit repetitive or burst firing of action potentials. A single neuronal Kv7 channel is a heterotetramer composed of two Kv7.2 and two Kv7.3 subunits. BFNE and EE mutations in Kv7.2 and Kv7.3 lead to decreased surface expression along the axon, which means less potassium ions are moved across the axonal membrane where action potentials are generated and …