Digital Commons Network^™

Il-8 Produced Via Bidirectional Communication Between Prostate Cancer And M2 Macrophages As A Potential Diagnostic And Prognostic Biomarker, Huihui Fan, Zheng Tang, Yaling Tian, Qingsong Lv, Fangyin Zeng

Faculty, Staff and Student Publications

PURPOSE: Owing to the mortality associated with metastatic prostate cancer and the shortcomings of the current parameters in predicting the disease prognosis, we require the identification of viable biomarkers, which would help in the diagnosis and prognosis of the disease. We aimed to determine whether the interleukin-8 level in the tumor microenvironment could serve as a potential clinical diagnostic marker and prognostic factor for prostate cancer.

METHODS: The migration assay of prostate cancer cells was performed in an in vitro co-culture model. Cell lines PC3 and DU145 were divided into two groups and co-cultured with M0 and M2 macrophages, respectively. …

Exaptation And Evolutionary Adaptation In Nociceptor Mechanisms Driving Persistent Pain, Edgar T Walters

Faculty, Staff and Student Publications

Background: Several evolutionary explanations have been proposed for why chronic pain is a major clinical problem. One is that some mechanisms important for driving chronic pain, while maladaptive for modern humans, were adaptive because they enhanced survival. Evidence is reviewed for persistent nociceptor hyperactivity (PNH), known to promote chronic pain in rodents and humans, being an evolutionarily adaptive response to significant bodily injury, and primitive molecular mechanisms related to cellular injury and stress being exapted (co-opted or repurposed) to drive PNH and consequent pain.

Summary: PNH in a snail (Aplysia californica), squid (Doryteuthis pealeii), fruit fly (Drosophila melanogaster), mice, rats, …

Effect Of Acute And Repeated Noise Exposure On The Behaviour And Lipid Peroxidation In Brain Tissue Of Male And Female Mice, Gabriella Korsós, Kinga Fodor, Annamária Kiss, Anna Blázovics, Sándor György Fekete

Turkish Journal of Veterinary & Animal Sciences

Despite the increasingly obvious sex differences, male animals are still predominantly used to study stress and related disorders. The aim of this study was to evaluate the effects of repeated noise stress in female and male mice. In the experiment, 12 male and 12 and female SPF/VAF 6-week-old Crl:CD1(lcr) mice were used. After 5 days of acclimatization all animals were placed in the open-field for three consecutive days where each mouse spent 10 min daily without any noise treatment in order to get used to the circumstances of the test. On day 9 to record baseline behaviour the animals were …

Optical Coherence Tomography For Dynamic Investigation Of Mammalian Reproductive Processes, Kohei Umezu, Irina V Larina

Faculty, Staff and Students Publications

The biological events associated with mammalian reproductive processes are highly dynamic and tightly regulated by molecular, genetic, and biomechanical factors. Implementation of live imaging in reproductive research is vital for the advancement of our understanding of normal reproductive physiology and for improving the management of reproductive disorders. Optical coherence tomography (OCT) is emerging as a promising tool for dynamic volumetric imaging of various reproductive processes in mice and other animal models. In this review, we summarize recent studies employing OCT-based approaches toward the investigation of reproductive processes in both, males and females. We describe how OCT can be applied to …

TCf21 Marks Visceral Adipose Mesenchymal Progenitors And Functions As A Rate-Limiting Factor During Visceral Adipose Tissue Development, Qianglin Liu, Chaoyang Li, Buhao Deng, Peidong Gao, Leshan Wang, Yuxia Li, Mohammad Shiri, Fozi Alkaifi, Junxing Zhao, Jacqueline M. Stephens, Constantine A. Simintiras, Joseph Francis, Jiangwen Sun, Xing Fu

Computer Science Faculty Publications

Distinct locations of different white adipose depots suggest anatomy-specific developmental regulation, a relatively understudied concept. Here, we report a population of Tcf21 lineage cells (Tcf21 LCs) present exclusively in visceral adipose tissue (VAT) that dynamically contributes to VAT development and expansion. During development, the Tcf21 lineage gives rise to adipocytes. In adult mice, Tcf21 LCs transform into a fibrotic or quiescent state. Multiomics analyses show consistent gene expression and chromatin accessibility changes in Tcf21 LC, based on which we constructed a gene-regulatory network governing Tcf21 LC activities. Furthermore, …

Targeting Hiv-1 Reservoirs In T Cell Subsets, Min Li, Marietta M Budai, Min Chen, Jin Wang

Faculty, Staff and Students Publications

The HIV-1 reservoirs harbor the latent proviruses that are integrated into the host genome. It is a challenging task to eradicate the proviruses in order to achieve an HIV cure. We have described a strategy for the clearance of HIV-1 infection through selective elimination of host cells harboring replication-competent HIV (SECH), by inhibition of autophagy and promotion of apoptosis during viral re-activation. HIV-1 can infect various CD4+ T cell subsets, but it is not known whether the SECH approach is equally effective in targeting HIV-1 reservoirs in these different subsets in vivo. In a humanized mouse model, we found …

Hippo Signaling: Advances In Potential Therapeutic Targets For Sinoatrial Node Disorders, Julianna N Quinn, Jun Wang

Faculty, Staff and Student Publications

The cardiac conduction system (CCS) propagates electrical impulses, generates cardiac contractions, and ultimately ensures regular heartbeats. Disruptions within the CCS lead to cardiac arrhythmias, which are known to be the leading cause of cardiac-related mortalities in humans. The sinoatrial node (SAN) is a key component of the CCS and functions as the natural cardiac pacemaker to initiate normal cardiac impulse and conduction. The SAN is characterized by significant heterogeneity and contains various cell types, including pacemaker cells that spontaneously generate action potentials to maintain a constant beating rhythm. The fundamental Hippo signaling pathway plays a key role in heart development …

Sox9 Governs Gastric Mucous Neck Cell Identity And Is Required For Injury-Induced Metaplasia, Spencer G Willet, Nattapon Thanintorn, Helen Mcneill, Sung-Ho Huh, David M Ornitz, Won Jae Huh, Stella G Hoft, Richard J Dipaolo, Jason C Mills

2020-Current year OA Pubs

BACKGROUND & AIMS: Acute and chronic gastric injury induces alterations in differentiation within the corpus of the stomach called pyloric metaplasia. Pyloric metaplasia is characterized by the death of parietal cells and reprogramming of mitotically quiescent zymogenic chief cells into proliferative, mucin-rich spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Overall, pyloric metaplastic units show increased proliferation and specific expansion of mucous lineages, both by proliferation of normal mucous neck cells and recruitment of SPEM cells. Here, we identify Sox9 as a potential gene of interest in the regulation of mucous neck and SPEM cell identity in the stomach.

METHODS: We used immunostaining …

Spatial Analysis Of Nanoparticle Distribution In Human Breast Xenografts Reveals Nanoparticles Targeted To Cancer Cells Localized With Tumor-Associated Stromal Cells, Sean Healy, Elizabeth T Henderson, Suqi Ke, Jacqueline Kelly, Brian W Simons, Chen Hu, Robert Ivkov, Preethi Korangath

Faculty, Staff and Students Publications

The biological influence of physicochemical parameters of “targeted” nanoparticles on their delivery to cancer tumors remains poorly understood. A comparative analysis of nanoparticle distributions in tumors following systemic delivery across several models can provide valuable insights.

Methods: Bionized nanoferrite nanoparticles (iron oxide core coated with starch), either conjugated with a targeted anti-HER2 antibody (BH), or unconjugated (BP), were intravenously injected into athymic nude or NOD-scid gamma (NSG) female mice bearing one of five human breast cancer tumor xenografts growing in a mammary fat pad. Tumors were harvested 24 hours after nanoparticle injection, fixed, mounted, and stained. We performed detailed histopathology …

Vaccine-Linked Chemotherapy Improves Cardiac Structure And Function In A Mouse Model Of Chronic Chagas Disease, Kathryn M Jones, Elise N Mangin, Corey L Reynolds, Liliana E Villanueva, Julio Vladimir Cruz, Leroy Versteeg, Brian Keegan, April Kendricks, Jeroen Pollet, Fabian Gusovsky, Maria Elena Bottazzi, Peter J Hotez

Faculty, Staff and Students Publications

INTRODUCTION: Chagas disease, caused by chronic infection with the protozoan parasite Trypanosoma cruzi, affects 6-7 million people worldwide. The major clinical manifestation of Chagas disease is chronic Chagasic cardiomyopathy (CCC), which encompasses a spectrum of symptoms including arrhythmias, hypertrophy, dilated cardiomyopathy, heart failure, and sudden death. Current treatment is limited to two antiparasitic drugs, benznidazole (BNZ) and nifurtimox, but both have limited efficacy to halt the progression of CCC. We developed a vaccine-linked chemotherapy strategy using our vaccine consisting of recombinant Tc24-C4 protein and a TLR-4 agonist adjuvant in a stable squalene emulsion, in combination with low dose benznidazole treatment. …

Sox9 Governs Gastric Mucous Neck Cell Identity And Is Required For Injury-Induced Metaplasia, Spencer G Willet, Nattapon Thanintorn, Helen Mcneill, Sung-Ho Huh, David M Ornitz, Won Jae Huh, Stella G Hoft, Richard J Dipaolo, Jason C Mills

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Acute and chronic gastric injury induces alterations in differentiation within the corpus of the stomach called pyloric metaplasia. Pyloric metaplasia is characterized by the death of parietal cells and reprogramming of mitotically quiescent zymogenic chief cells into proliferative, mucin-rich spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Overall, pyloric metaplastic units show increased proliferation and specific expansion of mucous lineages, both by proliferation of normal mucous neck cells and recruitment of SPEM cells. Here, we identify Sox9 as a potential gene of interest in the regulation of mucous neck and SPEM cell identity in the stomach.

METHODS: We used immunostaining …

Effects Of Aging On Urinary Tract Epithelial Homeostasis And Immunity, Marianne M Ligon, Chetanchandra S Joshi, Bisiayo E Fashemi, Arnold M Salazar, Indira U Mysorekar

Faculty, Staff and Students Publications

A global increase in older individuals creates an increasing demand to understand numerous healthcare challenges related to aging. This population is subject to changes in tissue physiology and the immune response network. Older individuals are particularly susceptible to infectious diseases, with one of the most common being urinary tract infections (UTIs). Postmenopausal and older women have the highest risk of recurrent UTIs (rUTIs); however, why rUTIs become more frequent after menopause and during old age is incompletely understood. This increased susceptibility and severity among older individuals may involve functional changes to the immune system with age. Aging also has substantial …

Cell-Type-Specific Aging Clocks To Quantify Aging And Rejuvenation In Neurogenic Regions Of The Brain, Matthew T Buckley, Eric D Sun, Benson M George, Ling Liu, Nicholas Schaum, Lucy Xu, Jaime M Reyes, Margaret A Goodell, Irving L Weissman, Tony Wyss-Coray, Thomas A Rando, Anne Brunet

Faculty, Staff and Students Publications

The diversity of cell types is a challenge for quantifying aging and its reversal. Here we develop 'aging clocks' based on single-cell transcriptomics to characterize cell-type-specific aging and rejuvenation. We generated single-cell transcriptomes from the subventricular zone neurogenic region of 28 mice, tiling ages from young to old. We trained single-cell-based regression models to predict chronological age and biological age (neural stem cell proliferation capacity). These aging clocks are generalizable to independent cohorts of mice, other regions of the brains, and other species. To determine if these aging clocks could quantify transcriptomic rejuvenation, we generated single-cell transcriptomic datasets of neurogenic …

Selective Reprogramming Of Regulatory T Cells In Solid Tumors Can Strongly Enhance Or Inhibit Tumor Growth, Rami Alfar, John V Napoleon, Imrul Shahriar, Richard Finnell, Cole Walchle, Austin Johnson, Philip S Low

Faculty, Staff and Students Publications

Folate receptor delta (FRδ) has been used as a biomarker for regulatory T cells (Tregs), because its expression is limited to Tregs and ovum. Although FRδ is unable to bind folate, we have used molecular docking software to identify a folate congener that binds FRδ with high affinity and have exploited this FRδ-specific ligand to target attached drugs (imaging agents, immune activators, and immune suppressors) specifically to Tregs in murine tumor xenografts. Analysis of treated tumors demonstrates that targeting of a Toll-like receptor 7 agonist inhibits Treg expression of FOXP3, PD-1, CTLA4, and HELIOS, resulting in 40-80% reduction in tumor …

The Nr2f2-Hand2 Signaling Axis Regulates Progesterone Actions In The Uterus At Early Pregnancy, Yeongseok Oh, Elvis Quiroz, Tianyuan Wang, Yassmin Medina-Laver, Skylar Montague Redecke, Francisco Dominguez, John P Lydon, Francesco J Demayo, San-Pin Wu

Faculty, Staff and Students Publications

Endometrial function is dependent on a tight crosstalk between the epithelial and stromal cells of the endometrium. This communication is critical to ensure a fertile uterus and relies on progesterone and estrogen signaling to prepare a receptive uterus for embryo implantation in early pregnancy. One of the key mediators of this crosstalk is the orphan nuclear receptor NR2F2, which regulates uterine epithelial receptivity and stromal cell differentiation. In order to determine the molecular mechanism regulated by NR2F2, RNAseq analysis was conducted on the uterus of

Oocyte-Specific Wee1-Like Protein Kinase 2 Is Dispensable For Fertility In Mice, Kaori Nozawa, Zian Liao, Yuhkoh Satouh, Ting Geng, Masahito Ikawa, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Wee1-like protein kinase 2 (WEE2) is an oocyte-specific protein tyrosine kinase involved in the regulation of oocyte meiotic arrest in humans. As such, it has been proposed as a candidate for non-hormonal female contraception although pre-clinical models have not been reported. Therefore, we developed two novel knockout mouse models using CRISPR/Cas9 to test loss-of-function of Wee2 on female fertility. A frameshift mutation at the Wee2 translation start codon in exon 2 had no effect on litter size, litter production, or the ability of oocytes to maintain prophase I arrest. Because of the lack of a reproductive phenotype, we additionally generated …

Myeloid-Associated Differentiation Marker Is Associated With Type 2 Asthma And Is Upregulated By Human Rhinovirus Infection, Sasipa Tanyaratsrisakul, Alane Blythe C Dy, Francesca Polverino, Mari Numata, Julie G Ledford

Faculty, Staff and Students Publications

BACKGROUND: Human rhinoviruses are known to predispose infants to asthma development during childhood and are often associated with exacerbations in asthma patients. MYADM epithelial expression has been shown to associate with asthma severity. The goal of this study was to determine if MYADM expression patterns were altered in asthma and/or rhinovirus infection and if increased MYADM expression is associated with increased asthma-associated factors.

METHODS: Utilizing H1HeLa cells and differentiated primary human airway epithelial cells (AECs), we measured the expression of MYADM and inflammatory genes by qRT-PCR in the presence or absence of RV-1B infection or poly I:C treatment and with …

Cc16 Drives Vla-2-Dependent Splunc1 Expression, Natalie Iannuzo, Holly Welfley, Nicholas C Li, Michael D L Johnson, Joselyn Rojas-Quintero, Francesca Polverino, Stefano Guerra, Xingnan Li, Darren A Cusanovich, Paul R Langlais, Julie G Ledford

Faculty, Staff and Students Publications

RATIONALE: CC16 (Club Cell Secretory Protein) is a protein produced by club cells and other non-ciliated epithelial cells within the lungs. CC16 has been shown to protect against the development of obstructive lung diseases and attenuate pulmonary pathogen burden. Despite recent advances in understanding CC16 effects in circulation, the biological mechanisms of CC16 in pulmonary epithelial responses have not been elucidated.

OBJECTIVES: We sought to determine if CC16 deficiency impairs epithelial-driven host responses and identify novel receptors expressed within the pulmonary epithelium through which CC16 imparts activity.

METHODS: We utilized mass spectrometry and quantitative proteomics to investigate how CC16 deficiency …

Gut Check: Assessing The Role Of The Gut Microbiota In The Adverse Cardiovascular Effects Of Obstructive Sleep Apnoea, David J Durgan, Ramon Farré

Faculty, Staff and Students Publications

No abstract provided.

The Role Of Vaccination Route With An Adenovirus-Vectored Vaccine In Protection, Viral Control, And Transmission In The Sars-Cov-2/K18-Hace2 Mouse Infection Model, Alexandria Dickson, Elizabeth Geerling, E Taylor Stone, Mariah Hassert, Tara L Steffen, Taneesh Makkena, Madeleine Smither, Katherine E Schwetye, Jianfeng Zhang, Bertrand Georges, M Scot Roberts, John J Suschak, Amelia K Pinto, James D Brien

2020-Current year OA Pubs

INTRODUCTION: Vaccination is the most effective mechanism to prevent severe COVID-19. However, breakthrough infections and subsequent transmission of SARS-CoV-2 remain a significant problem. Intranasal vaccination has the potential to be more effective in preventing disease and limiting transmission between individuals as it induces potent responses at mucosal sites.

METHODS: Utilizing a replication-deficient adenovirus serotype 5-vectored vaccine expressing the SARS-CoV-2 RBD (AdCOVID) in homozygous and heterozygous transgenic K18-hACE2, we investigated the impact of the route of administration on vaccine immunogenicity, SARS-CoV-2 transmission, and survival.

RESULTS: Mice vaccinated with AdCOVID via the intramuscular or intranasal route and subsequently challenged with SARS-CoV-2 showed …

Adeno-Associated Virus 8 Delivers An Immunomodulatory Peptide To Mouse Liver More Efficiently Than To Rat Liver, Yuqing Wang, Ayrea Hurley, Marco De Giorgi, Mark R Tanner, Rong-Chi Hu, Michael W Pennington, William R Lagor, Christine Beeton

Faculty, Staff and Students Publications

Targeting the Kv1.3 potassium channel has proven effective in reducing obesity and the severity of animal models of autoimmune disease. Stichodactyla toxin (ShK), isolated from the sea anemone Stichodactyla helianthus, is a potent blocker of Kv1.3. Several of its analogs are some of the most potent and selective blockers of this channel. However, like most biologics, ShK and its analogs require injections for their delivery, and repeated injections reduce patient compliance during the treatment of chronic diseases. We hypothesized that inducing the expression of an ShK analog by hepatocytes would remove the requirement for frequent injections and lead to a …

Therapeutic Activity Of Lipoxin A4 In Tio2-Induced Arthritis In Mice: Nf-Κb And Nrf2 In Synovial Fluid Leukocytes And Neuronal Trpv1 Mechanisms, Telma Saraiva-Santos, Tiago H Zaninelli, Felipe A Pinho-Ribeiro, Et Al.

2020-Current year OA Pubs

BACKGROUND: Lipoxin A4 (LXA

METHODS: Mice were stimulated with TiO

RESULTS: LXA

CONCLUSION: LXA

Lymphatic Contractile Dysfunction In Mouse Models Of Cantú Syndrome With Katp Channel Gain-Of-Function, Michael J Davis, Jorge A Castorena-Gonzalez, Hae Jin Kim, Min Li, Maria Remedi, Colin G Nichols

2020-Current year OA Pubs

Cantú Syndrome (CS) is an autosomal dominant disorder caused by gain-of-function (GoF) mutations in the Kir6.1 and SUR2 subunits of K

Inhibition Of Mirna Associated With A Disease-Specific Signature And Secreted Via Extracellular Vesicles Of Systemic Lupus Erythematosus Patients Suppresses Target Organ Inflammation In A Humanized Mouse Model, Nicholas A Young, Emily Schwarz, Braden M Zeno, Shane Bruckner, Rosana A Mesa, Kyle Jablonski, Lai-Chu Wu, Elisha D O Roberson, Wael N Jarjour

2020-Current year OA Pubs

INTRODUCTION: Distinct, disease-associated intracellular miRNA (miR) expression profiles have been observed in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematous (SLE) patients. Additionally, we have identified novel estrogenic responses in PBMCs from SLE patients and demonstrated that estrogen upregulates toll-like receptor (TLR)7 and TLR8 expression. TLR7 and TLR8 bind viral-derived single-stranded RNA to stimulate innate inflammatory responses, but recent studies have shown that miR-21, mir-29a, and miR-29b can also bind and activate these receptors when packaged and secreted in extracellular vesicles (EVs). The objective of this study was to evaluate the association of EV-encapsulated small RNA species in SLE …

Elevated Liver Glycogenolysis Mediates Higher Blood Glucose During Acute Exercise In Barth Syndrome, George G. Schweitzer, Grace L. Ditzenberger, Curtis C. Hughey, Brian N. Finck, Michael R. Martino, Christina A. Pacak, Barry J. Byrne, William Todd Cade

2020-Current year OA Pubs

UNLABELLED: Barth syndrome (BTHS) is an X-linked recessive genetic disorder due to mutations in the Tafazzin (TAFAZZIN) gene that lead to cardiac and skeletal muscle mitochondrial dysfunction. Previous studies in humans with BTHS demonstrate that the defects in muscle mitochondrial oxidative metabolism result in an enhanced reliance on anaerobic metabolism during exercise to meet energy demands of muscular work. During exercise, the liver normally increases glucose production via glycogenolysis and gluconeogenesis to match the elevated rate of muscle glucose uptake and meet the ATP requirements of working muscle. However, the impact of Tafazzin deficiency on hepatic glucose production and the …

Phagocytosis Is A Primary Determinant Of Pulmonary Clearance Of Clinical Klebsiella Pneumoniae Isolates, Rick Van Der Geest, Hongye Fan, Hernán F Peñaloza, William G Bain, Zeyu Xiong, Naina Kohli, Emily Larson, Mara L G Sullivan, Jonathan M Franks, Donna B Stolz, Ryota Ito, Kong Chen, Yohei Doi, Melanie J Harriff, Janet S Lee

2020-Current year OA Pubs

INTRODUCTION:

METHODS: We screened 19 clinical respiratory

RESULTS: The respiratory

CONCLUSION: Altogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical

Transferrin Receptor In Primary And Metastatic Breast Cancer: Evaluation Of Expression And Experimental Modulation To Improve Molecular Targeting, Francesca Fontana, Alison K. Esser, Christopher Egbulefu, Partha Karmakar, Xinming Su, John S. Allen, Yalin Xu, Jennifer L. Davis, Ariel Gabay, Jingyu Xiang, Kristin A. Kwakwa, Brad Manion, Suzanne Bakewell, Shunqiang Li, Haeseong Park, Gregory M. Lanza, Samuel Achilefu, Katherine N. Weilbaecher

2020-Current year OA Pubs

BACKGROUND: Conjugation of transferrin (Tf) to imaging or nanotherapeutic agents is a promising strategy to target breast cancer. Since the efficacy of these biomaterials often depends on the overexpression of the targeted receptor, we set out to survey expression of transferrin receptor (TfR) in primary and metastatic breast cancer samples, including metastases and relapse, and investigate its modulation in experimental models.

METHODS: Gene expression was investigated by datamining in twelve publicly-available datasets. Dedicated Tissue microarrays (TMAs) were generated to evaluate matched primary and bone metastases as well as and pre and post chemotherapy tumors from the same patient. TMA were …

Enhancing The Therapeutic Activity Of Hyperimmune Igg Against Chikungunya Virus Using Fcγriiia Affinity Chromatography, Julie M Fox, Vicky Roy, Bronwyn M Gunn, Glen R Bolton, Daved H Fremont, Galit Alter, Michael S Diamond, Austin W Boesch

2020-Current year OA Pubs

INTRODUCTION: Chikungunya virus (CHIKV) is a re-emerging mosquito transmitted alphavirus of global concern. Neutralizing antibodies and antibody Fc-effector functions have been shown to reduce CHIKV disease and infection in animals. However, the ability to improve the therapeutic activity of CHIKV-specific polyclonal IgG by enhancing Fc-effector functions through modulation of IgG subclass and glycoforms remains unknown. Here, we evaluated the protective efficacy of CHIKV-immune IgG enriched for binding to Fc-gamma receptor IIIa (FcγRIIIa) to select for IgG with enhanced Fc effector functions.

METHODS: Total IgG was isolated from CHIKV-immune convalescent donors with and without additional purification by FcγRIIIa affinity chromatography. The …

Inhibition Of Yap/Taz-Driven Tead Activity Prevents Growth Of Nf2-Null Schwannoma And Meningioma, Liyam Laraba, Lily Hillson, Julio Grimm De Guibert, Amy Hewitt, Maisie R Jaques, Tracy T Tang, Leonard Post, Emanuela Ercolano, Ganesha Rai, Shyh-Ming Yang, Daniel J Jagger, Waldemar Woznica, Philip Edwards, Aditya G Shivane, C Oliver Hanemann, David B Parkinson

Peninsula Medical School

Schwannoma tumours typically arise on the eighth cranial nerve and are mostly caused by loss of the tumour suppressor Merlin (NF2). There are no approved chemotherapies for these tumours and the surgical removal of the tumour carries a high risk of damage to the eighth or other close cranial nerve tissue. New treatments for schwannoma and other NF2-null tumours such as meningioma are urgently required. Using a combination of human primary tumour cells and mouse models of schwannoma, we have examined the role of the Hippo signalling pathway in driving tumour cell growth. Using both genetic ablation of the Hippo …

Vancomycin-Induced Gut Microbial Dysbiosis Alters Enteric Neuron-Macrophage Interactions During A Critical Period Of Postnatal Development, Ellen Merrick Schill, Elisabeth L Joyce, Alexandria N Floyd, Sreeram Udayan, Brigida Rusconi, Shreya Gaddipati, Bibiana E Barrios, Vini John, Mitchell E Kaye, Devesha H Kulkarni, Jocelyn T Pauta, Keely G Mcdonald, Rodney D Newberry

2020-Current year OA Pubs

Vancomycin is a broad-spectrum antibiotic widely used in cases of suspected sepsis in premature neonates. While appropriate and potentially lifesaving in this setting, early-life antibiotic exposure alters the developing microbiome and is associated with an increased risk of deadly complications, including late-onset sepsis (LOS) and necrotizing enterocolitis (NEC). Recent studies show that neonatal vancomycin treatment disrupts postnatal enteric nervous system (ENS) development in mouse pups, which is in part dependent upon neuroimmune interactions. This suggests that early-life antibiotic exposure could disrupt these interactions in the neonatal gut. Notably, a subset of tissue-resident intestinal macrophages, muscularis macrophages, has been identified as …