Medical Microbiology Commons^™

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,

Exploring Oxylipins In Host–Microbe Interactions And Their Impact On Infection And Immunity, Robert J. Neff, Christopher D. Radka

Markey Cancer Center Faculty Publications

Plasma lipids are essential components of biological systems, transported through interactions with proteins to maintain cellular functions. These lipids exist in various forms, such as fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenol lipids, derived from dietary intake, adipose tissue, and biosynthesis. While the association between certain fatty acids and cardiovascular diseases has been widely recognized, polyunsaturated fatty acids (PUFAs) exhibit cardioprotective effects, reducing risks of arrhythmias and heart-related mortality. This is due to their role in the production of eicosanoids, which modulate inflammation. Chronic inflammation, particularly in obesity, is significantly influenced by fatty acids, with saturated fatty acids promoting …

Extracellular Vesicles Released By All Patients Contain Hne-Adducted Proteins: Implications Of Collateral Damage., Jenni Ho, Suriyan Sukati, Tamara Taylor, Sherry Carter, Brittany Fuller, Amy Marmo, Caryn Sorge, John D'Orazio, D Allan Butterfield, Subbarao Bondada, Heidi Weiss, Daret K St Clair, Luksana Chaiswing

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Off-target neuronal injury is a serious side-effect observed in cancer survivors. It has previously been shown that pediatric acute lymphoblastic leukemia (ALL) survivors have a decline in neurocognition compared to healthy age-matched counterparts. Elevated oxidative stress has been documented to be a mediator in off-target tissue damage in cancer survivors. Early detection of oxidative stress markers may provide an opportunity to prevent off-target tissue damage. Extracellular vesicles (EVs) have surfaced as a potential diagnostic tool due to molecular cargo they contain. We investigated the potential for EVs to be a sensitive indicator of oxidative stress and off-target tissue damage by …

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 …

Characterization Of Vaccine-Enhanced Humoral Immune Responses Against Emergent Sars-Cov-2 Variants In A Convalescent Cohort, Jared Sheehan, Amber J. Trauth, Michael E. Hagensee, Alistair J. Ramsay

School of Graduate Studies Faculty Publications

Vaccination of COVID-19–convalescent individuals may generate ‘hybrid’ immunity of enhanced magnitude, durability, and cross-reactive breadth. Our primary goal was to characterize hybrid antibody (Ab) responses in a patient cohort infected with ancestral Wuhan-Hu-1 virus and vaccinated between 6 and 10 months later with the Wuhan-Hu-1–based BNT162b2 mRNA vaccine. We were particularly interested in determining the efficacy of neutralizing Ab responses against subsequently emergent SARS-CoV-2 variants. Sera collected at 3-monthly intervals over a period of 12 months were analyzed by ELISA for SARS-CoV-2 RBD–specific Ab responses, and also for neutralizing Ab activity using pseudovirus-based neutralization assays. We found that convalescent RBD-reactive …

Borreliosis And Doxycycline Treatment Disrupt Gut Microbiota And Immune Responses In Nonhuman Primates, Ethan G. Napier, Isaac R. Cinco, Sheridan B. Wagner, Ethan V. Stuart, Qi Qiao, Joshua Taylor, Brian Stevenson, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi (Bb) is the spirochete that causes Lyme disease (LD). Transmission to humans occurs via bites of infected Ixodes spp. ticks. Doxycycline is often used to treat LD patients, which is sometimes delayed due to current diagnostic challenges. Recently, several lines of evidence show dysbiosis of the gut microbiome in LD patients, which may be a host factor contributing to pathogenesis and symp tomology but is still an understudied area in the field. To address this knowledge gap, we longitudinally compared the immune response and gut microbial composi tion of Japanese macaques after intradermal infection with Bb strain 297 …

The Role Of Horizontal Gene Transfer In Antibiotic Resistance Amidst Prevalent Community And Healthcare-Associated Mrsa Rates, Gabrielle Nascimento

Honors College Theses

In recent decades, cases of community-acquired MRSA (CA-MRSA) and healthcare-associated MRSA (HA-MRSA) have been on the rise. The ability of antibiotic resistance to transfer between microorganisms greatly expands its threat to the effective treatment and containment of bacterial infections. The mecA gene is found on a mobile cassette within the Staphylococcal cell and encodes for PBP2a, an alternate version of penicillin-binding protein (PBP) with less binding affinity for β-lactam antibiotics, increasing resistance to the effects of antibiotics. The goal of this research is to investigate the horizontal transfer of the mecA gene between various Staphylococcus species as well as to …

Chronic Alcohol Consumption Induces Phenotypic And Functional Alterations Consistent With A Hyper-Inflammatory State In Peripheral Blood Mononuclear Cell-Derived Microglia In A Rhesus Macaque Model, Hami Hemati, Madison B. Blanton, Heather E. True, Jude Koura, Rupak Khadka, Kathleen A. Grant, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Alcohol-induced dysregulation of microglial activity is associated with neuroinflammation, cognitive decline, heightened risk for neurodegenerative diseases, alcohol dependence, and escalation of alcohol drinking. Given the challenge of longitudinally sampling primary microglia, we optimized an in vitro method to differentiate peripheral blood mononuclear cells (PBMC) from rhesus macaque (RM) into induced microglia-like cells (RM-iMGLs). The RM-iMGLs displayed transcriptional profiles distinct from monocyte progenitors and closely resembling primary microglia. Notably, morphological features showed that differentiated RM-iMGLs derived from subjects with chronic alcohol consumption (CAC), while bigger, exhibited a bipolar-like morphology. Additionally, dysregulation in key inflammatory and regulatory markers, along with increased baseline …

Investigating Regulation And The Regulome Of The Nucleic Acid Binding Protein Spovg Within Borrelia Burgdorferi, Timothy C. Saylor

Theses and Dissertations--Medical Sciences

Prior studies indicated Borrelia burgdorferi SpoVG protein was regulated, SpoVG binds specifically to a number of nucleic acids, and SpoVG binds to the non-variable section of the major virulence factor vlsE. Although a direct transcriptional activator or inhibitor was not elucidated, it is shown that SpoVG is regulated based on cell culture density independent of the growth rate of B. burgdorferi, indicating that SpoVG regulation is outside the scope of the alternative sigma factor RpoS. Using a dCas9 CRISPRi construct to target SpoVG resulted in protein expression trending towards upregulation of the BosR-RpoS regulon, and a marked decrease …

Impact Of Obesity On The Gut Microbiome And Inflammatory Markers During Siv Infection And Antiretroviral Therapy, Casey M. Mcguire, Isaac R. Cinco, Diana Takahashi, Kristin A. Sauter, Melissa Kirigiti, Ilhem Messaoudi, Jonah B. Sacha, Charles T. Roberts, Paul Kievit

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Dysbiosis and impaired gut barrier integrity contribute to chronic immune activation associated with both obesity and HIV infection. Given the increased incidence of obesity in people living with HIV, we explored the impact of obesity on the gut microbiome and microbial translocation (MT) biomarkers during HIV infection and antiretroviral therapy (ART). Lean and obese rhesus macaques were infected with simian immunodeficiency virus (SIV) and subsequently treated with ART. Obese animals exhibited higher initial MT and inflammation biomarkers that remained constant throughout the study, while lean animals exhibited significant increases in these biomarkers that approached levels observed in obese animals. Lean …

Intracellular Survival Of Staphylococcus Aureus In Macrophages During Osteomyelitis, William A. Lathram, Christopher D. Radka

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Staphylococcus aureus, traditionally viewed as an extracellular pathogen, is increasingly recognized for its ability to persist intracellularly, particularly within macrophages. This intracellular lifestyle is central to osteomyelitis, a chronic bone infection characterized by persistent inflammation, bone destruction, and impaired repair. Within bone, S. aureus exploits macrophage plasticity by driving a shift from pro-inflammatory, bactericidal M1-like states to anti-inflammatory, tissue-reparative M2-like phenotypes. This polarization suppresses immune clearance and promotes an environment conducive to bacterial survival and dissemination. Additional strategies – including biofilm formation, small colony variants, and inhibition of phagolysosomal killing – further enhance persistence and immune evasion. While these …

Development Of A Proposed Selective Medium For The Isolation And Differentiation Of P. Sordellii, Dimyana Bottros

Honors Undergraduate Theses

Clostridium, a genus of anaerobic, spore-forming bacteria, includes clinically and ecologically significant species like Clostridium difficile and Paeniclostridium sordellii. C. difficile causes antibiotic-associated colitis, while P. sordellii is linked to fatal infections and spontaneous abortions. Recent studies found both species in marine sediments, suggesting their role in environmental and wildlife health disturbances, including the 2013 mass mortality of over 300 manatees in the Indian River Lagoon. However, isolating and differentiating P. sordellii is challenging due to the lack of selective media optimized for its growth. This thesis proposes a novel selective medium tailored to P. sordellii’s physiological …

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 …

Multi-Antigen Elephant Endotheliotropic Herpesvirus (Eehv) Mrna Vaccine Induces Humoral And Cell-Mediated Responses In Mice, Jessica R Watts, Jennifer L Spencer Clinton, Jeroen Pollet, Rongsheng Peng, Jie Tan, Paul D Ling

Faculty, Staff and Students Publications

Background/Objectives: Elephant endotheliotropic herpesvirus (EEHV) causes lethal hemorrhagic disease (HD) in Asian and African elephants in human care and the wild. It is the leading cause of death for young Asian elephants in North American and European zoos despite sensitive diagnostic tests and improved treatments. Thus, there is a critical need to develop an effective vaccine to prevent severe illness and reduce mortality from EEHV-HD. We generated a multi-antigenic EEHV mRNA vaccine to address this need that encodes the EEHV1A-subtype glycoproteins gB, gH, gL, and gO. These conserved proteins are the entry machinery for several herpesviruses in the betaherpesvirus subfamily …

Uba1 Inhibition Sensitizes Cancer Cells To Parp Inhibitors, Sharad Awasthi, Lacey E Dobrolecki, Christina Sallas, Xudong Zhang, Yang Li, Sima Khazaei, Sumanta Ghosh, Collene R Jeter, Jinsong Liu, Gordon B Mills, Shannon N Westin, Michael T Lewis, Weiyi Peng, Anil K Sood, Timothy A Yap, S Stephen Yi, Daniel J Mcgrail, Nidhi Sahni

Faculty, Staff and Students Publications

Therapeutic strategies targeting the DNA damage response, such as poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi), have revolutionized cancer treatment in tumors deficient in homologous recombination (HR). However, overcoming innate and acquired resistance to PARPi remains a significant challenge. Here, we employ a genome-wide CRISPR knockout screen and discover that the depletion of ubiquitin-activating enzyme E1 (UBA1) enhances sensitivity to PARPi in HR-proficient ovarian cancer cells. We show that silencing or pharmacological inhibition of UBA1 sensitizes multiple cell lines and organoid models to PARPi. Mechanistic studies uncover that UBA1 inhibition not only impedes HR repair to sensitize cells to PARP inhibition …

Development Of A Ripk1 Degrader To Enhance Antitumor Immunity, Xin Yu, Dong Lu, Xiaoli Qi, Rishi Ram Paudel, Hanfeng Lin, Bryan L Holloman, Feng Jin, Longyong Xu, Lang Ding, Weiyi Peng, Meng C Wang, Xi Chen, Jin Wang

Faculty, Staff and Students Publications

The scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and emerges as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain of RIPK1, here we harness proteolysis targeting chimera (PROTAC) technology to develop a RIPK1 degrader, LD4172. LD4172 exhibits potent and selective RIPK1 degradation both in vitro and in vivo. Degradation of RIPK1 by LD4172 triggers immunogenic cell death, enhances tumor-infiltrating lymphocyte responses, and sensitizes tumors to anti-PD1 therapy in female C57BL/6J mice. This work reports …

The Rise, Fall, And Resurgence Of Phage Therapy For Urinary Tract Infection, Jacob J Zulk, Kathryn A Patras, Anthony W Maresso

Faculty, Staff and Students Publications

In the face of rising antimicrobial resistance, bacteriophage therapy, also known as phage therapy, is seeing a resurgence as a potential treatment for bacterial infections including urinary tract infection (UTI). Primarily caused by uropathogenic Escherichia coli, the 400 million UTI cases annually are major global healthcare burdens and a primary cause of antibiotic prescriptions in the outpatient setting. Phage therapy has several potential advantages over antibiotics including the ability to disrupt bacterial biofilms and synergize with antimicrobial treatments with minimal side effects or impacts on the microbiota. Phage therapy for UTI treatment has shown generally favorable results in recent …

Amniotic Fluid-Derived Stem Cells: Potential Factories Of Natural And Mimetic Strategies For Congenital Malformations, Cristiane S R Fonteles, Julia Enterria-Rosales, Ying Lin, John W Steele, Ramiro A Villarreal-Leal, Jing Xiao, Daniel I Idowu, Beck Burgelin, Bogdan J Wlodarczyk, Richard H Finnell, Bruna Corradetti

Faculty, Staff and Students Publications

BACKGROUND: Mesenchymal stem cells (MSCs) derived from gestational tissues offer a promising avenue for prenatal intervention in congenital malformations although their application is hampered by concerns related to cellular plasticity and the need for invasive, high-risk surgical procedures. Here, we present naturally occurring exosomes (EXOs) isolated from amniotic fluid-derived MSCs (AF-MSCs) and their mimetic analogs (MIMs) as viable, reproducible, and stable alternatives. These nanovesicles present a minimally invasive therapeutic option, addressing the limitations of MSC-based treatments while retaining therapeutic efficacy.

METHODS: MIMs were generated from AF-MSCs by combining sequential filtration steps through filter membranes with different porosity and size exclusion …

Elucidating The Mechanism Of Interleukin-17a Signaling In The Pathogenesis Of West Nile Virus, Farzana Nazneen

Dissertations

West Nile Virus (WNV), a neurotropic flavivirus transmitted by mosquitoes, is a leading cause of viral encephalitis in the United States and remains a significant public health concern. Unfortunately, no vaccine or therapeutic intervention is available against WNV infection. Previous studies, including ours, demonstrated that interleukin-17A (IL-17A) signaling increases the cytotoxic potential of CD8⁺ T cells to facilitate WNV and parasite clearance; however, the molecular mechanism is not understood. IL-17 receptor C (IL-17RC) is an obligatory co-receptor with IL-17 receptor A (IL-17RA) for signaling induced by IL-17A, IL-17A/F, and IL-17F. In this study, we found that IL-17RC deficient ( …

Microbiome Variation In Production Phenotypes And The Role Of Colonization History In Microbiome Establishment, Seidu Adams

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Ruminant-based agriculture is expected to continue to be a major contributor to food security to feed the growing population. At the heart of nutrient degradation of complex organic matter within the rumen are its microbes. These microbes can convert otherwise unusable organic matter into usable protein and energy and can provide up to 50% of the animal’s protein needs and up to 70% of the energy needs. The microbial functional capacity within the rumen determines the nutrients utilized and the end products of fermentation. However, our understanding of microbial functional capacity within the rumen and factors that influence the rumen …

Association Between Microsatellite Instability Status, Clinicopathological Features And Mitochondrial Dna Amplification In Patients With Colorectal Cancer, Junmi Lu, Hong Tan, Tao Guo, Xi Chen, Zhongyi Tong

Faculty, Staff and Students Publications

The relationship between BRAF-V600E mutations, mitochondrial DNA amplification and microsatellite instability-high (MSI-H) in colorectal cancer (CRC) has yet to be fully elucidated. The aim of the present study was to assess the association between the MSI status and BRAF-V600E gene mutations/clinicopathological features/mitochondrial DNA amplification in CRC. A non-interventional study analysis was performed using the clinicopathological features of 455 patients with CRC. Immunohistochemistry was used to evaluate four mismatch repair proteins (MutS homolog 2, MutS homolog 6, MutL homolog 1 and postmeiotic segregation increased 2), Ki-67 index, and programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) expression. …

Multiple Factors Regulate The Expression Of Sufcdsub In Streptococcus Mutans, Kassapa Ellepola, Lauren C. Guillot, Bradley Comeaux, Yiran Han, Jessica K. Kajfasz, Jacob P. Bitoun, Grace Spatafora, Jose A. Lemos, Zezhang T. Wen

School of Dentistry Faculty Publications

Introduction: The sufCDSUB gene cluster, encoding the sole iron-sulfur (Fe-S) cluster assembly system in S. mutans, was recently shown to be up-regulated in response to oxidative stressors and Fe limitation. Methods: In this study, luciferase reporter fusion assays, electrophoretic gel mobility shift assays (EMSA) and in vitro transcription assays (IVT) were used to dissect the cis- and trans-acting factors that regulate the expression of sufCDSUB. Results and discussion: Results showed deletion of perR, for the only Fur-family transcriptional regulator in S. mutans, resulted in > 5-fold increases in luciferase activity under the control of the sufCDSUB promoter (P < 0.01), as compared to the parent strain, UA159 when the reporter strains were grown in medium with no supplemental iron. Site-directed mutagenesis of a PerR-box in the promoter region led to elevation of the reporter activity by >1.6-fold (P < 0.01). In an EMSA, recombinant PerR (rPerR) was shown to bind to the cognate sufCDSUB promoter leading to mobility retardation. On the other hand, the reporter activity was increased by > 84-fold …

Space: An Open-Source, Single-Cell Analysis Of Cell Painting Data, Fabio Stossi, Pankaj K Singh, Michela Marini, Kazem Safari, Adam T Szafran, Alejandra Rivera Tostado, Christopher D Candler, Maureen G Mancini, Elina A Mosa, Michael J Bolt, Demetrio Labate, Michael A Mancini

Faculty, Staff and Students Publications

Phenotypic profiling by high throughput microscopy, including Cell Painting, has become a leading tool for screening large sets of perturbations in cellular models. To efficiently analyze this big data, available open-source software requires computational resources usually not available to most laboratories. In addition, the cell-to-cell variation of responses within a population, while collected and analyzed, is usually averaged and unused. We introduce SPACe (Swift Phenotypic Analysis of Cells), an open-source platform for analysis of single-cell image-based morphological profiles produced by Cell Painting. We highlight several advantages of SPACe, including processing speed, accuracy in mechanism of action recognition, reproducibility across biological …

Limosilactobacillus Reuteri Ameliorates Maternal Separation Stress In Newborn Mice And Alters Subsequent Adult Behaviour, Z. M. Saleh, B. Okeugo, V. R. Venna, F. W. Blixt, V. A. Quaicoe, E. S. Park, S. Giorgberidze, Meng Luo, Christopher M. Taylor, J. M. Rhoads, Y. Liu

School of Medicine Faculty Publications

Maternal separation (MS) in mice results in behavioral deficits and gut microbiota dysbiosis that all persist into adulthood. Limosilactobacillus reuteri DSM 17938 modulates gut microbiota, alters systemic metabolites, and facilitates immune regulation. To assess the effect of DSM 17938 on biochemical and behavioural stress-associated changes, newborn mice were exposed to unpredictable MS (MSU) daily from day 7 to day 20 of life, with intragastric administration of DSM 17938 or PBS as control. Body weight, brain levels of cholecystokinin (CCK), glial fibrillary acidic protein (GFAP), corticosterone, and stool microbiota were assessed at day 21. Behaviour tests including Y-maze (YMT), Tail Suspension …

Camkk2: Bridging The Gap Between Ca2+ Signaling And Energy-Sensing, Luke M Mcaloon, Abbey G Muller, Kevin Nay, Eudora L Lu, Benoit Smeuninx, Anthony R Means, Mark A Febbraio, John W Scott

Faculty, Staff and Students Publications

Calcium (Ca2+) ions are ubiquitous and indispensable signaling messengers that regulate virtually every cell function. The unique ability of Ca2+ to regulate so many different processes yet cause stimulus specific changes in cell function requires sensing and decoding of Ca2+ signals. Ca2+-sensing proteins, such as calmodulin, decode Ca2+ signals by binding and modifying the function of a diverse range of effector proteins. These effectors include the Ca2+-calmodulin dependent protein kinase kinase-2 (CaMKK2) enzyme, which is the core component of a signaling cascade that plays a key role in important physiological and pathophysiological processes, including brain function and cancer. In addition …

Automatically Extracting Social Determinants Of Health For Suicide: A Narrative Literature Review, Annika M Schoene, Suzanne Garverich, Iman Ibrahim, Sia Shah, Benjamin Irving, Clifford C Dacso

Faculty, Staff and Students Publications

Suicide is a complex phenomenon that is often not preceded by a diagnosed mental health condition, therefore making it difficult to study and mitigate. Artificial Intelligence has increasingly been used to better understand Social Determinants of Health factors that influence suicide outcomes. In this review we find that many studies use limited SDoH information and minority groups are often underrepresented, thereby omitting important factors that could influence risk of suicide.

Gene Discovery From Microbial Gene Libraries I: Protection Against Reactive Oxygen Species-Driven Dna Damage, John C Taylor, Carmen Gu Liu, James D Chang, Brianna E Thompson, Anthony W Maresso

Faculty, Staff and Students Publications

Reactive oxygen species (ROS) pose a lethal risk for all life forms by causing damage to cell processes, genome-wide DNA damage-driving mutation, replicative instability, and death. Thus, the development of mechanisms to resist or repair ROS-induced DNA damage is critical for the reliable replication of nucleic acids. DNA repair and protection mechanisms have been discovered in all forms of life. However, the vast array of microbes that may harbor novel repair or protection mechanisms, especially bacterial viruses, have not been adequately assessed. Here, we screened a microbial gene library composed primarily of phage open reading frames (ORFs) to uncover elements …

Nerve Injury Inhibits Oprd1 And Cnr1 Transcription Through Rest In Primary Sensory Neurons, Ashok Subedi, Asieh Etemad, Aadhya Tiwari, Yuying Huang, Biji Chatterjee, Samantha M Mcleod, Yungang Lu, Diangelo Gonzalez, Krishna Ghosh, Mario Sirito, Sanjay K Singh, Elisa Ruiz, Sandra L Grimm, Cristian Coarfa, Hui-Lin Pan, Sadhan Majumder

Faculty, Staff and Students Publications

The transcription repressor REST in the dorsal root ganglion (DRG) is upregulated by peripheral nerve injury and promotes the development of chronic pain. However, the genes targeted by REST in neuropathic pain development remain unclear. The expression levels of four opioid receptor genes (Oprm1, Oprd1, Oprl1 and Oprk1) and the cannabinoid CB1 receptor (Cnr1) gene in the DRG regulate nociception. In this study, we determined the role of REST in controlling their expression in the DRG induced by spared nerve injury (SNI). SNI induced chronic pain hypersensitivity in wild-type mice and was accompanied by increased levels of Rest transcript and …

A Cross-Systems Primer For Synthetic Microbial Communities, Elijah C Mehlferber, Gontran Arnault, Bishnu Joshi, Laila P Partida-Martinez, Kathryn A Patras, Marie Simonin, Britt Koskella

Faculty, Staff and Students Publications

The design and use of synthetic communities, or SynComs, is one of the most promising strategies for disentangling the complex interactions within microbial communities, and between these communities and their hosts. Compared to natural communities, these simplified consortia provide the opportunity to study ecological interactions at tractable scales, as well as facilitating reproducibility and fostering interdisciplinary science. However, the effective implementation of the SynCom approach requires several important considerations regarding the development and application of these model systems. There are also emerging ethical considerations when both designing and deploying SynComs in clinical, agricultural or environmental settings. Here we outline current …

A Stronger Impact On Career Development For Early- And Mid-Career Faculty, Daniel A Gorelick, Jason Gertz, Kaitlin J Basham, Lindsey S Treviño

Faculty, Staff and Students Publications

Nuclear receptors are important in normal physiology and disease. Physicians and scientists who study nuclear receptors organize and attend conferences and symposia devoted to foundational and translational nuclear receptor research, but the field lacks a platform for early-stage investigators and aspiring leaders. In 2019, Zeynep Madak-Erdogan, Rebecca Riggins, and Matthew Sikora founded Nuclear Receptor (NR) Interdisciplinary Meeting for Progress And Collaboration Together (IMPACT, https://nrimpact.com), a collaborative group designed for early- and mid-career faculty who study nuclear receptors in any context or organism [1]. NR IMPACT addresses challenges for early- and mid-career faculty. Here, we review the progress of NR IMPACT …