Medical Genetics Commons^™

Inactivation Of The Fusobacterium Nucleatum Rnf Complex Reduces Fada-Mediated Amyloid Formation And Tumor Development, Timmie A Britton, Ju Huck Lee, Chungyu Chang, Aadil H Bhat, Yi-Wei Chen, Rusul Mohammed Ali, Chenggang Wu, Asis Das, Hung Ton-That

Faculty, Staff and Student Publications

The Gram-negative anaerobe Fusobacterium nucleatum is an oral oncobacterium that promotes colorectal cancer (CRC) development with the amyloid-forming cell surface adhesin FadA integral to CRC tumorigenesis. We describe here molecular genetic studies uncovering a novel mode of metabolic regulation of FadA-mediated tumor formation by a highly conserved respiratory enzyme known as the Rnf complex. First, we show that genetic disruption of Rnf, via rnfC deletion, significantly reduces the level of fadA transcript, accompanied by a near-complete abolishment of the precursor form of FadA (pFadA), reduced assembly of FadA at the mature cell pole, and severe defects in the osmotic stress-induced …

Enriched Pathways In Gut Microbiome Predict Response To Immune Checkpoint Inhibitor Treatment Across Demographic Regions And Various Cancer Types, Xunhui Cai, Jennifer Y Cho, Lijun Chen, Yufeng Liu, Fenghu Ji, Katia Salgado, Siyi Ge, Dehua Yang, Hui Yu, Jianbo Shao, P Andrew Futreal, Boris Sepesi, Don Gibbons, Yaobing Chen, Guoping Wang, Chao Cheng, Meng Wu, Jianjun Zhang, Ansel Hsiao, Tian Xia

Faculty, Staff and Student Publications

Understanding the effect of gut microbiota function on immune checkpoint inhibitor (ICI) responses is urgently needed. Here, we integrated 821 fecal metagenomes from 12 datasets to identify differentially abundant genes and construct random forest models to predict ICI response. Gene markers demonstrated excellent predictive performance, with an average area under the curve (AUC) of 0.810. Pathway analyses revealed that quorum sensing (QS), ABC transporters, flagellar assembly, and amino acid biosynthesis pathways were enriched between responders (R) and non-responders (NRs) across 12 datasets. Furthermore,

Nkapl Facilitates Transcription Pause-Release And Bridges Elongation To Initiation During Meiosis Exit, Zhenlong Kang, Chen Xu, Shuai Lu, Jie Gong, Ruoyu Yan, Gan Luo, Yuanyuan Wang, Qing He, Yifei Wu, Yitong Yan, Baomei Qian, Shenglin Han, Zhiwen Bu, Jinwen Zhang, Xian Xia, Liang Chen, Zhibin Hu, Mingyan Lin, Zheng Sun, Yayun Gu, Lan Ye

Faculty, Staff and Students Publications

Transcription elongation, especially RNA polymerase II (Pol II) pause-release, is less studied than transcription initiation in regulating gene expression during meiosis. It is also unclear how transcription elongation interplays with transcription initiation. Here, we show that depletion of NKAPL, a testis-specific protein distantly related to RNA splicing factors, causes male infertility in mice by blocking the meiotic exit and downregulating haploid genes. NKAPL binds to promoter-associated nascent transcripts and co-localizes with DNA-RNA hybrid R-loop structures at GAA-rich loci to enhance R-loop formation and facilitate Pol II pause-release. NKAPL depletion prolongs Pol II pauses and stalls the SOX30/HDAC3 transcription initiation complex …

In Vivo Evaluation Of Novel Nanoparticles And Repurposed Pharmaceuticals To Combat Antimicrobial Resistance, Sarah E. Evans

Theses, Dissertations and Capstones

In a 2019 report by the Centers for Disease Control and Prevention (CDC), infections resistant to antibiotic treatment amount to about three million infections and 48,000 deaths. Antimicrobial resistance is an escalating global threat as existing antibiotics lose efficacy over time. The project described is focused on partnering with pharmaceutical researchers and producers to test new nanoparticle-based or repurposed compounds. The central hypothesis of this thesis is that pharmaceutical formulations such as nanoparticles may provide a cost-effective means of combating the emerging antimicrobial resistance. The nanoparticle compounds allowed for a wide range of customization for the pharmaceutical design, since the …

The Dna Demethylase Tet1 Modifies The Impact Of Maternal Folic Acid Status On Embryonic Brain Development, Lehua Chen, Bernard K Van Der Veer, Qiuying Chen, Spyridon Champeris Tsaniras, Wannes Brangers, Harm H M Kwak, Rita Khoueiry, Yunping Lei, Robert Cabrera, Steven S Gross, Richard H Finnell, Kian Peng Koh

Faculty, Staff and Students Publications

Folic acid (FA) is well known to prevent neural tube defects (NTDs), but we do not know why many human NTD cases still remain refractory to FA supplementation. Here, we investigate how the DNA demethylase TET1 interacts with maternal FA status to regulate mouse embryonic brain development. We determined that cranial NTDs display higher penetrance in non-inbred than in inbred Tet1−/− embryos and are resistant to FA supplementation across strains. Maternal diets that are either too rich or deficient in FA are linked to an increased incidence of cranial deformities in wild type and Tet1+/− offspring and to …

5-Fluorouracil Induced Oxidative Stress Is Variable Across Triple Negative Breast Cancer Cell Lines, Rachel L. Walker

Departmental Honors & Graduate Capstone Projects

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with treatment limited to chemotherapy. However, not all patient tumors respond to chemotherapy. The variable cytotoxic effects of chemotherapies may be due to how cancer cells regulate reactive oxygen species (ROS). In this study, we examined two mouse breast cancer cell lines: 4T1 and EO771, vary when treated with hydrogen peroxide (H2O2) and 5-Fluorouracil (5FU), known ROS-inducing substances. In 4T1 cells H2O2 increased oxidized DNA but caused minimal cell death. While in EO771 cells that same amount of H2O2 caused complete apoptosis. Cell number, ROS, and cell death showed …

Construction And Characterization Of Dna Libraries From Cultured Phages And Environmental Viromes, Carmen Gu Liu, Brianna E Thompson, James D Chang, Lorna Min, Anthony W Maresso

Faculty, Staff and Students Publications

Despite many efforts to understand and leverage the functional potential of environmental viromes, most bacteriophage genes are largely uncharacterized. To explore novel biology from uncultivated microbes like phages, metagenomics has emerged as a powerful tool to directly mine new genes without the need to culture the diverse microbiota and the viruses within. When a pure computational approach cannot infer gene function, it may be necessary to create a DNA library from environmental genomic DNA, followed by the screening of that library for a particular function. However, these screens are often initiated without a metagenomic analysis of the completed DNA library …

Targeting Nuclear Receptor Coactivator Src-1 Prevents Colorectal Cancer Immune Escape By Reducing Transcription And Protein Stability Of Pd-L1, Yilin Hong, Qiang Chen, Zinan Wang, Yong Zhang, Bei Li, Hanshi Guo, Chuanzhong Huang, Xu Kong, Pingli Mo, Nengming Xiao, Jianming Xu, Yunbin Ye, Chundong Yu

Faculty, Staff and Students Publications

Programmed death-ligand 1 (PD-L1) is overexpressed in multiple cancers and critical for their immune escape. It has previously shown that the nuclear coactivator SRC-1 promoted colorectal cancer (CRC) progression by enhancing CRC cell viability, yet its role in CRC immune escape is unclear. Here, we demonstrate that SRC-1 is positively correlated with PD-L1 in human CRC specimens. SRC-1 deficiency significantly inhibits PD-L1 expression in CRC cells and retards murine CRC growth in subcutaneous grafts by enhancing CRC immune escape via increasing tumor infiltration of CD8

Persistence Of Daptomycin-Resistant And Vancomycin-Resistant Enterococci In Hospitalized Patients With Underlying Malignancies: A 7-Year Follow-Up Study, Lynn El Haddad, Georgios Angelidakis, Yuting Zhai, Layale Yaghi, Cesar A Arias, Samuel A Shelburne, Kwangcheol Casey Jeong, Roy F Chemaly

Faculty, Staff and Student Publications

Vancomycin-resistant enterococci (VRE) commonly colonize the gut of individuals with hematologic malignancies or undergoing hematopoietic cell transplant (HCT) and may cause bacteremia. In 2012, we identified VRE isolates from patients and patients' rooms and showed transmission networks of highly genetically related daptomycin-resistant (DR)-VRE strains. This is a follow-up study performing whole-genome sequencing (WGS) and phylogenetic analyses on 82 clinical VRE strains isolated from stools and blood cultures of patients with leukemia and HCT between 2015 and 2019. Here, we observed transmission of highly genetically related strains between rooms on the same or on different floors, including a DR-VRE strain identified …

Systemic Interindividual Dna Methylation Variants In Cattle Share Major Hallmarks With Those In Humans, Wen-Jou Chang, Maria S Baker, Eleonora Laritsky, Chathura J Gunasekara, Uditha Maduranga, Justine C Galliou, Joseph W Mcfadden, Jessica R Waltemyer, Bruce Berggren-Thomas, Brianna N Tate, Hanxue Zhang, Benjamin D Rosen, Curtis P Van Tassell, George E Liu, Cristian Coarfa, Yi Athena Ren, Robert A Waterland

Faculty, Staff and Students Publications

BACKGROUND: We recently identified ~ 10,000 correlated regions of systemic interindividual epigenetic variation (CoRSIVs) in the human genome. These methylation variants are amenable to population studies, as DNA methylation measurements in blood provide information on epigenetic regulation throughout the body. Moreover, establishment of DNA methylation at human CoRSIVs is labile to periconceptional influences such as nutrition. Here, we analyze publicly available whole-genome bisulfite sequencing data on multiple tissues of each of two Holstein cows to determine whether CoRSIVs exist in cattle.

RESULTS: Focusing on genomic blocks with ≥ 5 CpGs and a systemic interindividual variation index of at least 20, …

Novel Immunomodulatory Properties Of Adenosine Analogs Promote Their Antiviral Activity Against Sars-Cov-2, Giulia Monticone, Zhi Huang, Peter Hewins, Thomasina Cook, Oygul Mirzalieva, Brionna King, Kristina Larter, Taylor Miller-Ensminger, Maria D. Sanchez-Pino, Timothy P. Foster, Olga V. Nichols, Alistair J. Ramsay, Samarpan Majumder, Dorota Wyczechowska, Darlene Tauzier, Elizabeth Gravois, Judy S. Crabtree, Jone Garai, Li Li, Jovanny Zabaleta, Mallory T. Barbier, Luis Del Valle, Kellie A. Jurado, Lucio Miele

School of Medicine Faculty Publications

The COVID-19 pandemic reminded us of the urgent need for new antivirals to control emerging infectious diseases and potential future pandemics. Immunotherapy has revolutionized oncology and could complement the use of antivirals, but its application to infectious diseases remains largely unexplored. Nucleoside analogs are a class of agents widely used as antiviral and anti-neoplastic drugs. Their antiviral activity is generally based on interference with viral nucleic acid replication or transcription. Based on our previous work and computer modeling, we hypothesize that antiviral adenosine analogs, like remdesivir, have previously unrecognized immunomodulatory properties which contribute to their therapeutic activity. In the case …

Mustang: Multi-Sample Spatial Transcriptomics Data Analysis With Cross-Sample Transcriptional Similarity Guidance, Seyednami Niyakan, Jianting Sheng, Yuliang Cao, Xiang Zhang, Zhan Xu, Ling Wu, Stephen T C Wong, Xiaoning Qian

Faculty, Staff and Students Publications

Spatially resolved transcriptomics has revolutionized genome-scale transcriptomic profiling by providing high-resolution characterization of transcriptional patterns. Here, we present our spatial transcriptomics analysis framework, MUSTANG (MUlti-sample Spatial Transcriptomics data ANalysis with cross-sample transcriptional similarity Guidance), which is capable of performing multi-sample spatial transcriptomics spot cellular deconvolution by allowing both cross-sample expression-based similarity information sharing as well as spatial correlation in gene expression patterns within samples. Experiments on a semi-synthetic spatial transcriptomics dataset and three real-world spatial transcriptomics datasets demonstrate the effectiveness of MUSTANG in revealing biological insights inherent in the cellular characterization of tissue samples under study.

A Bioinformatic Analysis Of T-Cell Epitope Diversity In Sars-Cov-2 Variants: Association With Covid-19 Clinical Severity In The United States Population, Grace J. Kim, Jacob H. Elnaggar, Mallory Varnado, Amy K. Feehan, Darlene Tauzier, Rebecca Rose, Susanna L. Lamers, Maya Sevalia, Najah Nicholas, Elizabeth Gravois, Daniel Fort, Judy S. Crabtree, Lucio Miele

School of Graduate Studies Faculty Publications

Long-term immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the identification of T-cell epitopes affecting host immunogenicity. In this computational study, we explored the CD8+ epitope diversity estimated in 27 of the most common HLA-A and HLA-B alleles, representing most of the United States population. Analysis of 16 SARS-CoV-2 variants [B.1, Alpha (B.1.1.7), five Delta (AY.100, AY.25, AY.3, AY.3.1, AY.44), and nine Omicron (BA.1, BA.1.1, BA.2, BA.4, BA.5, BQ.1, BQ.1.1, XBB.1, XBB.1.5)] in analyzed MHC class I alleles revealed that SARS-CoV-2 CD8+ epitope conservation was estimated at 87.6%–96.5% in spike (S), 92.5%–99.6% in membrane (M), and 94.6%–99% in …

Histone Proteoform Analysis Reveals Epigenetic Changes In Adult Mouse Brown Adipose Tissue In Response To Cold Stress, Bethany C Taylor, Loic H Steinthal, Michelle Dias, Hari Krishna Yalamanchili, Scott A Ochsner, Gladys E Zapata, Nitesh R Mehta, Neil J Mckenna, Nicolas L Young, Alli M Nuotio-Antar

Faculty, Staff and Students Publications

BACKGROUND: Regulation of the thermogenic response by brown adipose tissue (BAT) is an important component of energy homeostasis with implications for the treatment of obesity and diabetes. Our preliminary analyses of RNA-Seq data uncovered many nodes representing epigenetic modifiers that are altered in BAT in response to chronic thermogenic activation. Thus, we hypothesized that chronic thermogenic activation broadly alters epigenetic modifications of DNA and histones in BAT.

RESULTS: Motivated to understand how BAT function is regulated epigenetically, we developed a novel method for the first-ever unbiased top-down proteomic quantitation of histone modifications in BAT and validated our results with a …

Effects Of Sars-Cov-2 Variants On Cd8+ T Cell Epitope Diversity: Estimating Clinical Severity In The United States, Grace Kim, Jacob Elnaggar, Maya Sevalia, Najah Nicholas, Mallory Varnado, Judy Crabtree, Lucio Miele

School of Medicine Faculty Publications

Association for Clinical and Translational Science 2024; April 3 - April 5, 2024; Las Vegas, NV

Genetic Ancestry And Radical Prostatectomy Findings In Hispanic/Latino Patients, Natalia L. Acosta-Vega, Rodolfo Varela, Jorge Andrés Mesa, Jone Garai, Alberto Gómez-Gutiérrez, Silvia J. Serrano-Gómez, Jovanny Zabaleta, María Carolina Sanabria-Salas, Alba L. Combita

School of Medicine Faculty Publications

Background: African ancestry is a known factor associated with the presentation and aggressiveness of prostate cancer (PC). Hispanic/Latino populations exhibit varying degrees of genetic admixture across Latin American countries, leading to diverse levels of African ancestry. However, it remains unclear whether genetic ancestry plays a role in the aggressiveness of PC in Hispanic/Latino patients. We explored the associations between genetic ancestry and the clinicopathological data in Hispanic/Latino PC patients from Colombia. Patients and methods: We estimated the European, Indigenous and African genetic ancestry, of 230 Colombian patients with localized/regionally advanced PC through a validated panel for genotypification of 106 Ancestry …

Identification Of An Early Survival Prognostic Gene Signature For Localized Osteosarcoma Patients, Tajhal D Patel, Sandra L Grimm, Rupa S Kanchi, Tanmay Gandhi, Amrit Koirala, Jason T Yustein, Cristian Coarfa

Faculty, Staff and Students Publications

Osteosarcoma is the most prevalent bone tumor in pediatric patients. Neoadjuvant chemotherapy has improved osteosarcoma patient survival, however the 5-year survival rate for localized osteosarcoma is 75% with a 30-50% recurrence rate. We, therefore, sought to identify a prognostic gene signature which could predict poor prognosis in localized osteosarcoma patients. Using the TARGET osteosarcoma transcriptomic dataset, we identified a 13-hub gene signature associated with overall survival and time to death of localized osteosarcoma patients, with the high-risk group showing a 22% and the low-risk group showing 100% overall survival. Furthermore, network analysis identified five modules of co-expressed genes that significantly …

Chimeric Systems Composed Of Swapped Tra Subunits Between Distantly-Related F Plasmids Reveal Striking Plasticity Among Type Iv Secretion Machines, Kouhei Kishida, Yang Grace Li, Natsumi Ogawa-Kishida, Pratick Khara, Abu Amar M Al Mamun, Rachel E Bosserman, Peter J Christie

Faculty, Staff and Student Publications

Bacterial type IV secretion systems (T4SSs) are a versatile family of macromolecular translocators, collectively able to recruit diverse DNA and protein substrates and deliver them to a wide range of cell types. Presently, there is little understanding of how T4SSs recognize substrate repertoires and form productive contacts with specific target cells. Although T4SSs are composed of a number of conserved subunits and adopt certain conserved structural features, they also display considerable compositional and structural diversity. Here, we explored the structural bases underlying the functional versatility of T4SSs through systematic deletion and subunit swapping between two conjugation systems encoded by the …

Multivalent Cytomegalovirus Glycoprotein B Nucleoside Modified Mrna Vaccines Did Not Demonstrate A Greater Antibody Breadth, Hsuan-Yuan Wang, Leike Li, Cody S Nelson, Richard Barfield, Sarah Valencia, Cliburn Chan, Hiromi Muramatsu, Paulo J C Lin, Norbert Pardi, Zhiqiang An, Drew Weissman, Sallie R Permar

Faculty, Staff and Student Publications

Human cytomegalovirus (HCMV) remains the most common congenital infection and infectious complication in immunocompromised patients. The most successful HCMV vaccine to date, an HCMV glycoprotein B (gB) subunit vaccine adjuvanted with MF59, achieved 50% efficacy against primary HCMV infection. A previous study demonstrated that gB/MF59 vaccinees were less frequently infected with HCMV gB genotype strains most similar to the vaccine strain than strains encoding genetically distinct gB genotypes, suggesting strain-specific immunity accounted for the limited efficacy. To determine whether vaccination with multiple HCMV gB genotypes could increase the breadth of anti-HCMV gB humoral and cellular responses, we immunized 18 female …

Genome-Wide P63-Target Gene Analyses Reveal Tap63/Nrf2-Dependent Oxidative Stress Responses, Marco Napoli, Avani A Deshpande, Deepavali Chakravarti, Kimal Rajapakshe, Preethi H Gunaratne, Cristian Coarfa, Elsa R Flores

Faculty, Staff and Students Publications

The p53 family member TP63 encodes two sets of N-terminal isoforms, TAp63 and ΔNp63 isoforms. They each regulate diverse biological functions in epidermal morphogenesis and in cancer. In the skin, where their activities have been extensively characterized, TAp63 prevents premature aging by regulating the quiescence and genomic stability of stem cells required for wound healing and hair regeneration, while ΔNp63 controls maintenance and terminal differentiation of epidermal basal cells. This functional diversity is surprising given that these isoforms share a high degree of similarity, including an identical sequence for a DNA-binding domain. To understand the mechanisms of the transcriptional programs …

Mitochondrial-Related Hub Genes In Dermatomyositis: Muscle And Skin Datasets-Based Identification And In Vivo Validation, Shuo Wang, Yiping Tang, Xixi Chen, Siyuan Song, Xi Chen, Qiao Zhou, Li Zeng

Faculty, Staff and Students Publications

Background: Mitochondrial dysfunction has been implicated in the pathogenesis of dermatomyositis (DM), a rare autoimmune disease affecting the skin and muscles. However, the genetic basis underlying dysfunctional mitochondria and the development of DM remains incomplete.

Methods: The datasets of DM muscle and skin tissues were retrieved from the Gene Expression Omnibus database. The mitochondrial related genes (MRGs) were retrieved from MitoCarta. DM-related modules in muscle and skin tissues were identified with the analysis of weighted gene co-expression network (WGCNA), and then compared with the MRGs to obtain the overlapping mitochondrial related module genes (mito-MGs). Subsequently, differential expression genes (DEGs) obtained …

Recombination-Mediated Dissemination Of Methicillin-Resistant S Aureus Clonal Complex 1 In The Egyptian Health Care Settings, Salma W Elsayed, Reem A Elghaish, Eman Badr, Shaimaa F Mouftah, Nehal A Saif, Iman S Naga, Ahmed H Shata, Ben Pascoe, Samuel K Sheppard, Mohamed Elhadidy

Faculty, Staff and Student Publications

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a rapidly evolving pathogen that is frequently associated with outbreaks and sustained epidemics. This study investigated the population structure, resistome, virulome, and the correlation between antimicrobial resistance determinants with phenotypic resistance profiles of 36 representative hospital-acquired MRSA isolates recovered from hospital settings in Egypt.

Results: The community-acquired MRSA lineage, clonal complex 1 (CC1) was the most frequently detected clone, followed by three other globally disseminated clones, CC121, CC8, and CC22. Most isolates carried SCCmec type V and more than half of isolates demonstrated multi-drug resistant phenotypes. Resistance to linezolid, a last resort antibiotic for …

The Role Of Noncoding Rnas In Pancreatic Birth Defects, Ziyue Zoey Yang, Ronald J Parchem

Faculty, Staff and Students Publications

Congenital defects in the pancreas can cause severe health issues such as pancreatic cancer and diabetes which require lifelong treatment. Regenerating healthy pancreatic cells to replace malfunctioning cells has been considered a promising cure for pancreatic diseases including birth defects. However, such therapies are currently unavailable in the clinic. The developmental gene regulatory network underlying pancreatic development must be reactivated for in vivo regeneration and recapitulated in vitro for cell replacement therapy. Thus, understanding the mechanisms driving pancreatic development will pave the way for regenerative therapies. Pancreatic progenitor cells are the precursors of all pancreatic cells which use epigenetic changes …

Mechanistic Toxicology In Light Of Genetic Compensation, Mary Jane Elizalde, Daniel A Gorelick

Faculty, Staff and Students Publications

Mechanistic toxicology seeks to identify the molecular and cellular mechanisms by which toxicants exert their deleterious effects. One powerful approach is to generate mutations in genes that respond to a particular toxicant, and then test how such mutations change the effects of the toxicant. CRISPR is a rapid and versatile approach to generate mutations in cultured cells and in animal models. Many studies use CRISPR to generate short insertions or deletions in a target gene and then assume that the resulting mutation, such as a premature termination codon, causes a loss of functional protein. However, recent studies demonstrate that this …

Molecular Mechanisms Of Twist1-Regulated Transcription In Emt And Cancer Metastasis, Xiaobin Yu, Tao He, Zhangwei Tong, Lan Liao, Shixia Huang, Walid D Fakhouri, Dean P Edwards, Jianming Xu

Faculty, Staff and Students Publications

TWIST1 induces epithelial-to-mesenchymal transition (EMT) to drive cancer metastasis. It is yet unclear what determines TWIST1 functions to activate or repress transcription. We found that the TWIST1 N-terminus antagonizes TWIST1-regulated gene expression, cancer growth and metastasis. TWIST1 interacts with both the NuRD complex and the NuA4/TIP60 complex (TIP60-Com) via its N-terminus. Non-acetylated TWIST1-K73/76 selectively interacts with and recruits NuRD to repress epithelial target gene transcription. Diacetylated TWIST1-acK73/76 binds BRD8, a component of TIP60-Com that also binds histone H4-acK5/8, to recruit TIP60-Com to activate mesenchymal target genes and MYC. Knockdown of BRD8 abolishes TWIST1 and TIP60-Com interaction and TIP60-Com recruitment to …

Development Of A Xylose-Inducible Promoter And Riboswitch Combination System For Manipulating Gene Expression In Fusobacterium Nucleatum, Bibek G C, Peng Zhou, Arindam Naha, Jianhua Gu, Chenggang Wu

Faculty, Staff and Student Publications

Inducible gene expression systems are important for studying bacterial gene function, yet most exhibit leakage. In this study, we engineered a leakage-free hybrid system for precise gene expression controls in Fusobacterium nucleatum by integrating the xylose-inducible expression system with the theophylline-responsive riboswitch. This innovative method enables concurrent control of target gene expression at both transcription and translation initiation levels. Using luciferase and the indole-producing enzyme tryptophanase (TnaA) as reporters, we demonstrated that the hybrid system displays virtually no observable signal in the absence of inducers. We employed this system to express FtsX, a protein related to fusobacterial cytokinesis, in an …

Effect Of Various Types Of Extracellular Dna On V Hyugaensis Biofilm Formation, Carmen Gu Liu, Anthony W Maresso

Faculty, Staff and Students Publications

Marine bacteria face a constant influx of new extracellular DNA (exDNA) due to the massive viral lysis that occurs in the ocean on a daily basis. Generally, biofilms have shown to be induced by self-secreted exDNA. However, the effect of various types of exDNA with varying lengths, self vs non-self, as well as guanine-cytosine content (GC) content on biofilm formation has not been explored, despite being a critical component of the extracellular polymeric substance. To test the effect of such exDNA on biofilms, a marine bioluminescent bacterium (Vibrio hyugaensis) was isolated from the Sippewissett Salt Marsh, USA, and …

Effect Of Exogenous L-Carnitine On Aortic Stiffness In Dyslipidemic Adolescents: Design Of A Quadruple-Blind, Randomized, Controlled Interventional Trial, Justin P Zachariah, Sandra Pena, Philip J Lupo, Nagireddy Putluri, Daniel J Penny, Melissa A Richard

Faculty, Staff and Students Publications

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) risk factors including vascular remodeling leading to hypertension and dyslipidemia are prevalent among children and adolescents. Conflicting observational and Mendelian randomization data suggest endogenous carnitine may affect arterial stiffness and lipid traits. Because of this, we developed a study to evaluate the causal role for carnitine in arterial stiffness at a point when the lifecourse trajectory to hypertension can be modified.

METHODS: This study is a mechanistic, double-blinded, randomized control trial (RCT) in 166 adolescents with dyslipidemia for the effect of 6 months of maximum dose 3 g daily oral l-carnitine supplementation (CS+) versus placebo …

Gwas-Identified Telomere Length Associated Genetic Variants Predict Risk Of Recurrence Of Hpv-Positive Oropharyngeal Cancer After Definitive Radiotherapy, Peng Sun, Peng Wei, Hongliang Liu, Jia Wu, Neil D Gross, Andrew G Sikora, Qingyi Wei, Sanjay Shete, Mark E Zafereo, Jisheng Liu, Guojun Li

Faculty, Staff and Student Publications

Background: Lymphocyte telomere length (LTL)-related genetic variants may modulate LTL and affect recurrence of squamous cell carcinoma of the oropharynx (SCCOP).

Methods: A total of 1013 patients with incident SCCOP were recruited and genotyped for 16 genome-wide association study (GWAS)-identified TL-related polymorphisms. Of these patients, 489 had tumour HPV16 status determination. Univariate and multivariate analyses were performed to evaluate associations.

Findings: Of the 16 TL-related polymorphisms, four were significantly associated with LTL: rs1920116, rs3027234, rs6772228, and rs11125529, and the patients with putatively favourable genotypes had approximately 1.5-3 times the likelihood of shorter LTL compared with patients with the corresponding risk …

Unravelling Spatial Gene Associations With Seagal: A Python Package For Spatial Transcriptomics Data Analysis And Visualization, Linhua Wang, Chaozhong Liu, Yang Gao, Xiang H-F Zhang, Zhandong Liu

Faculty, Staff and Students Publications

SUMMARY: In the era where transcriptome profiling moves toward single-cell and spatial resolutions, the traditional co-expression analysis lacks the power to fully utilize such rich information to unravel spatial gene associations. Here, we present a Python package called Spatial Enrichment Analysis of Gene Associations using L-index (SEAGAL) to detect and visualize spatial gene correlations at both single-gene and gene-set levels. Our package takes spatial transcriptomics datasets with gene expression and the aligned spatial coordinates as input. It allows for analyzing and visualizing genes' spatial correlations and cell types' colocalization within the precise spatial context. The output could be visualized as …