Medical Sciences Commons^™

Id1 And Id3 Functions In The Modulation Of The Tumour Immune Microenvironment In Adult Patients With B-Cell Acute Lymphoblastic Leukaemia, Nathaly Poveda-Garavito, Carlos A. Orozco Castaño, Yulieth Torres-Llanos, Nataly Cruz-Rodriguez, Rafael Parra-Medina, Sandra Quijano, Jovanny Zabaleta, Alba Lucia Combita

School of Medicine Faculty Publications

Introduction: B-cell acute lymphoblastic leukemia (B-ALL) in adults often presents a poor prognosis. ID1 and ID3 genes have been identified as predictors of poor response in Colombian adult B-ALL patients, contributing to cancer development. In various cancer models, these genes have been associated with immune regulatory populations within the tumor immune microenvironment (TIME). B-ALL progression alters immune cell composition and the bone marrow (BM) microenvironment, impacting disease progression and therapy response. This study investigates the relationship between ID1 and ID3 expression, TIME dynamics, and immune evasion mechanisms in adult B-ALL patients. Methods: This exploratory study analysed BM samples from 10 …

Role Of Myeloid Cell-Specific Adenylyl Cyclase Type 7 In Lipopolysaccharide- And Alcohol-Induced Immune Responses, Yawen Hu, Sonika Patial, Yogesh Saini, Masami Yoshimura

School of Graduate Studies Faculty Publications

Clinical and experimental evidence indicates that alcohol use causes various abnormalities in the immune system and compromises immune functions. However, the mechanistic understanding of ethanol’s effects on the immune system remains limited. Cyclic AMP (cAMP) regulates multiple processes, including immune responses. Earlier research indicated that type 7 adenylyl cyclase (AC7) regulates the immune system and is highly responsive to ethanol. Therefore, we hypothesized that AC7 is a central player in regulating the effects of alcohol on innate immune responses. To test this hypothesis, we utilized a myeloid lineage-specific AC7 KO mouse model and compared the effects of acute and chronic …

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 …

Enhancing Immune Response And Survival In Hepatocellular Carcinoma With Novel Oncolytic Jurona Virus And Immune Checkpoint Blockade, Mulu Z. Tesfay, Yuguo Zhang, Khandoker U. Ferdous, Mika A. Taylor, Aleksandra Cios, Randal S. Shelton, Camila C. Simoes, Chelsae R. Watters, Oumar Barro, Natalie M. Elliott, Bahaa Mustafa, Jean Christopher Chamcheu, Alicia L. Graham, Charity L. Washam, Duah Alkam, Allen Gies, Stephanie D. Byrum, Emmanouil Giorgakis, Steven R. Post, Thomas Kelly, Jun Ying, Omeed Moaven, Chiswili Y. Chabu, Martin E. Fernandez-Zapico, Dan G. Duda, Lewis R. Roberts, Rang Govindarajan, Mitesh J. Borad, Martin J. Cannon, Et Al

School of Graduate Studies Faculty Publications

Members of the Vesiculovirus genus including Jurona virus (JURV) have emerged as promising immunotherapeutic agents, characterized by their tumor selectivity, fast kinetics, low seroprevalence, and minimal toxicity in humans. Here, we demonstrate that the administration of JURV leads to tumor regression in both hepatocellular carcinoma (HCC) xenograft and syngeneic models. Furthermore, our findings indicate that combining JURV and anti-PD-1 therapy reduced tumor burden and improved survival rates over JURV or anti-PD-1 alone in an orthotopic HCC model. Proteogenomic analysis of JURV-treated, murine HCC tumors demonstrates that the therapeutic effects of the combination of JURV and anti-PD-1 are predominantly driven by …

Avaren-Fc, A Novel Immunotherapeutic, Recruits Nk Cells In B16f10 Melanoma Tumor Tissue, Sreevatsa Vemuri, Katarina L Mayer, Nobuyuki Matoba

The Cardinal Edge

Melanoma is the fifth most common cancer in the US, with limited effective immunotherapeutic options available for patients. Avaren-Fc (AvFc) is a novel experimental immunotherapeutic agent with a unique “lectibody” property. It is capable of targeting cancer cells through the selective recognition of high mannose glycans, which are aberrantly overrepresented on the surface of malignant cells. Upon binding to cancer cells, AvFc can interact with circulating effector immune cells equipped with Fc receptors, such as natural killer (NK) cells to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and kill the cancer cells. Previous work has shown that AvFc effectively induces ADCC activity …

Autoimmunity And The Epigenome, Jeffrey S. Miller Jr

The Cardinal Edge

No abstract provided.

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 …

Immune Responses Drive Chorioretinitis And Retinal Pathology After Neonatal Cmv Infection, Jessica L. Mccord, John Y.S. Han, Ross E. Staudt, Nancy J. Philp Phd, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Human cytomegalovirus (CMV) causes a common congenital infection leading to long-term neurological impairments including brain, cochlear, and ocular pathology. Infection of newborn mice with murine (M)CMV is an established model of neuropathology caused by congenital CMV infection, with recent work suggesting that brain pathology may be driven by immune responses. In the eye, however, CMV retinitis is thought to result from virus-driven necrosis in the absence of T cell responses. We found that MCMV infection of newborn mice recapitulates human eye disease after congenital CMV infection, including focal chorioretinitis, inflamed vasculature, and disrupted blood-retinal barriers. Moreover, infection drove extensive T …

The Impact Of Diabetes Mellitus On Hiv Virologic Control: Results Of The Macs/Wihs Combined Cohort Study, Sarah C Mann, Weiqun Tong, Alison G Abraham, Frank Palella, Anjali Sharma, Phyllis C Tien, Margaret A Fischl, Samy I Mcfarlane, Cecile D Lahiri, Susan Koletar, Daniel Merenstein, Michelle Floris-Moore, Jordan E Lake, Elizabeth Daubert, Aubri Hickman, Todd T Brown, Jose Castillo-Mancilla

Faculty, Staff and Student Publications

Objective: Diabetes mellitus (DM) is associated with lower antiretroviral (ART) drug exposure among persons with HIV (PWH) compared to PWH without DM. The association between DM and virologic control in PWH, however, remains unknown.

Methods: We included participants in the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study (MWCCS) who had initiated ART between 1999 and 2020 and had a suppressed HIV viral load (≤200 copies/ml) within 1 year of ART initiation. We compared the frequency of incident HIV viremia (HIV-1 RNA >200 copies/ml) between adult PWH with and without DM. Poisson regression was used to examine the …

Alternatively Spliced Map4 Isoforms Have Key Roles In Maintaining Microtubule Organization And Skeletal Muscle Function, Lathan Lucas, Larissa Nitschke, Brandon Nguyen, James A Loehr, George G Rodney, Thomas A Cooper

Faculty, Staff and Students Publications

Skeletal muscle cells (myofibers) are elongated non-mitotic, multinucleated syncytia that have adapted a microtubule lattice. Microtubule-associated proteins (MAPs) play roles in regulating microtubule architecture. The most abundant MAP in skeletal muscle is MAP4. MAP4 consists of a ubiquitous MAP4 isoform (uMAP4), expressed in most tissues, and a striated-muscle-specific alternatively spliced isoform (mMAP4) that includes a 3,180-nucleotide exon (exon 8). To determine the role of mMAP4 in skeletal muscle, we generated mice that lack mMAP4 and express only uMAP4 due to genomic deletion of exon 8. We demonstrate that loss of mMAP4 leads to disorganized microtubule architecture and intrinsic loss of …

Skin Manifestations In People With Hepatitis C, Erjola Toska, Cameron Minars, Suzanne Riskin

HCA-NSU MD Research Day

Skin Manifestations in People with Hepatitis C Authors: Erjola Toska, OMS-III, Cameron Minars, OMS-II, Suzanne Riskin, M.D. Objectives: This study is aimed to summarize the association between hepatitis C infection and dermatological manifestations from the past decade. Background: Hepatitis C is a growing global health concern, with rising incidence rates and an increased likelihood of extrahepatic manifestations, including dermatological conditions. Despite research into the connection between hepatitis C and skin disorders, there is a lack of comprehensive reviews on this subject. Methods: Four databases—PubMed (NLM), EMBASE, CINAHL, and Web of Science—were searched for peer-reviewed articles written in English, focusing on …

Nosebleed No More: Recognizing And Diagnosing Factor Viii Inhibitor, Salam Harb, Leidy Huie Martinez Md, Jose Alvarado Md, Ajit Koli Do, Hazem Nasef Ms4

HCA-NSU MD Research Day

Acquired hemophilia is a condition characterized by the unexpected onset of severe bleeding due to an issue with coagulation factors. Typically, this disorder results from the production of autoantibodies against the Factor VIII coagulation factor. Although acquired hemophilia is an extremely rare condition, with an annual incidence of just 1.5 cases per million, it is crucial to recognize and understand it. This is because diagnosing this disorder is intricate, and if left undiagnosed and untreated, it can lead to high levels of morbidity and mortality. This case stands out as the condition typically targets older adults, with around 80% of …

Mouse Mammary Tumor Virus (Mmtv) Genomic Rna (Grna) Packaging: Selective Grna Encapsidation Is Facilitated By Long-Range Interactions (Lris) That Facilitate Specific Gag Binding, Suresha G. Prabhu

Thesis/ Dissertation Defenses

Mouse mammary tumor virus (MMTV) is a betaretrovirus that induces breast cancer and sporadically, T-cell lymphomas in mice. MMTV serves as a pertinent model for elucidating the mechanism(s) of oncogenesis and the genetics associated with the development of mammary tumors. Being a rodent retrovirus, MMTV is phylogenetically distant from human and other primate retroviruses; thus, positioning it ideally as a potential vector of choice for human gene therapy. This may circumvent safety concerns such as recombination with other related endogenous human retroviruses. In addition, MMTV is distinct from most other retroviruses, but similar to lentiviruses, in that it has the …

The Rna Receptor Rig-I Binding Synthetic Oligodeoxynucleotide Promotes Pneumonia Survival, Yongxing Wang, Vikram V Kulkarni, Jezreel Pantaleóngarcía, Michael K Longmire, Mathilde Lethier, Stephen Cusack, Scott E Evans

Faculty, Staff and Student Publications

Pneumonia is a worldwide threat to public health, demanding novel preventative and therapeutic strategies. The lung epithelium is a critical environmental interface that functions as a physical barrier to pathogen invasion while also actively sensing and responding to pathogens. We have reported that stimulating lung epithelial cells with a combination therapeutic consisting of a diacylated lipopeptide and a synthetic CpG oligodeoxynucleotide (ODN) induces synergistic pneumonia protection against a wide range of pathogens. We report here that mice deficient in TLR9, the previously described receptor for ODN, still displayed partial ODN-induced protection. This prompted us to seek an alternate ODN receptor, …

Using A Rabbit Model To Understand The Impact Of Oral Versus Intravenous Transmission Of Epstein-Barr Virus, Meera Mohammed Al Ameri

Thesis/ Dissertation Defenses

The isolation of Epstein-Barr Virus (EBV) in 1964 from a case of Burkitt lymphoma prompted a surge in research on the biology of this oncogenic virus and its role in the pathogenesis of associated malignancies. Over half a century later, a number of pertinent questions on the dynamics of EBV and the cellular targets of primary infection remain poorly defined. One major obstacle in EBV research has been the lack of a suitable small animal model. EBV is a highly human tropic virus. We have recently established a novel rabbit model of EBV infection that appears to mimic natural infection …

Peak Nasal Inspiratory Flow Assessment Of Polyp Size And Response From Synapse, Amber U Luong, Joshua M Levy, Ludger Klimek, Richard J Harvey, Jared Silver, Steven G Smith, Abby Fuller, Robert Chan, Peter W Hellings

Faculty, Staff and Student Publications

Background: In the phase III SYNAPSE study, mepolizumab plus standard of care reduced total endoscopic nasal polyp score (NPS) versus that with placebo in patients with chronic rhinosinusitis with nasal polyps.

Objective: Our aim was to investigate relationships between NPS and (1) peak nasal inspiratory flow (PNIF) and (2) patient-reported outcomes.

Methods: In this post hoc analysis, patients randomized 1:1 received mepolizumab, 100 mg, or placebo subcutaneously every 4 weeks (plus standard of care). Changes from baseline in PNIF (week 52), visual analog scale scores (overall symptoms, nasal obstruction, and loss of smell [weeks 49-52]), and total 22-Item Sino-Nasal Outcome …

Ga2len Anacare Consensus Statement: Potential Of Omalizumab In Food Allergy Management, Torsten Zuberbier, Antonella Muraro, Ulugbek Nurmatov, Stefania Arasi, Katarina Stevanovic, Aikaterini Anagnostou, Roberta Bonaguro, Sharon Chinthrajah, Gideon Lack, Alessandro Fiocchi, Thuy-My Le, Paul Turner, Montserrat Alvaro Lozano, Elizabeth Angier, Simona Barni, Phillippe Bégin, Barbara Ballmer-Weber, Victoria Cardona, Carsten Bindslev-Jensen, Antonella Cianferoni, Nicolette De Jong, Debra De Silva, Antoine Deschildre, Audrey Dunn Galvin, Motohiro Ebisawa, David M Fleischer, Jennifer Gerdts, Mattia Giovannini, Josefine Gradman, Susanne Halken, Syed Hasan Arshad, Ekaterina Khaleva, Susanne Lau, Richard Loh, Mika J Mäkelä, Mary Jane Marchisotto, Laura Morandini, Charlotte G Mortz, Caroline Nilsson, Anna Nowak-Wegrzyn, Marcia Podestà, Lars K Poulsen, Graham Roberts, Pablo Rodríguez Del Río, Hugh A Sampson, Angel Sánchez, Sabine Schnadt, Peter K Smith, Hania Szajewska, Natasa Teovska Mitrevska, Alice Toniolo, Carina Venter, Amena Warner, Gary W K Wong, Robert Wood, Margitta Worm

Faculty, Staff and Students Publications

Immunoglobulin E (IgE)‐mediated food allergies are the most common type of food allergy, often causing rapid symptoms after exposure to allergens posing a serious health risk and a high impact on patient's and caregiver's quality of life. Omalizumab, a humanized anti‐IgE monoclonal antibody, reduces allergic reactions by binding to circulating IgE. Omalizumab has been successfully used in allergic asthma, chronic rhinosinusitis with nasal polyps, and chronic urticaria, and was recently approved for treating IgE‐mediated food allergies by the US Food and Drug Administration (FDA). This GA2LEN ANACARE Consensus Statement presents our position on the use of omalizumab for treating IgE‐mediated …

Experiences Of Midwestern Obstetric Clinicians During The Coronavirus Disease 2019 Pandemic, Drishti D Sinha, Megan Foeller, Abigail S Bell, Anthony J Nixon, Darrell Hudson, Aimee S James, Amy R Scheffer, Ana A Baumann, Emily Diveley, Ebony B Carter, Nandini Raghuraman, Indira U Mysorekar, Jeannie C Kelly

Faculty, Staff and Students Publications

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic led to healthcare system changes aimed at minimizing disease transmission that impacted experiences with obstetric healthcare.

OBJECTIVE: To explore experiences of clinicians providing obstetric care during the COVID-19 pandemic.

STUDY DESIGN: Qualitative, in-depth, semi-structured interviews were conducted with five nurse practitioners and 16 obstetrical physicians providing a mix of outpatient and inpatient obstetric care during the COVID-19 pandemic in a mid-sized, Midwestern city in the United States. Interviews elucidated challenges and facilitators of obstetric care provision and vaccination of pregnant patients against COVID-19 during the pandemic. Transcripts were coded inductively then deductively using …

Hepatotoxicity Induced By Immune Checkpoint Inhibitors, Flaviu Muresan, Olga Hilda Orasan, Angela Cozma, Madalina Daiana Bancos, Lorena Ciumarnean, Mircea Vasile Milaciu, Tinca Codruta Pocol, Nicoleta Valentina Leach, Teodora Gabriela Alexescu, Ovidiu Vasile Fabian, George Ciulei, Mirela Georgiana Perne

Journal of Mind and Medical Sciences

Immune checkpoint inhibitors (ICIs) are an effective immunotherapeutic approach for cancers affecting the lung, skin, kidney, mammary gland, or certain hematologic malignancies. Regarding the prognosis of these oncological conditions, treatments with ICIs open new therapeutic perspectives with benefits for both patients and healthcare providers. A drawback of immune checkpoint inhibition is the occurrence of immune-related adverse events that can involve a wide range of organs, such as the liver. Given widespread usage of immunotherapy, the number of patients who suffer from this unwanted condition has increased. Hepatopathy induced by ICIs can be severe and can even lead to death. Detecting …

Riluzole Attenuates Acute Neural Injury And Reactive Gliosis, Hippocampal-Dependent Cognitive Impairments And Spontaneous Recurrent Generalized Seizures In A Rat Model Of Temporal Lobe Epilepsy, Thomas Kyllo, Dominic Allocco, Laine Vande Hei, Heike Wulff, Jeffrey D. Erickson

School of Medicine Faculty Publications

Background: Riluzole exhibits neuroprotective and therapeutic effects in several neurological disease models associated with excessive synaptic glutamate (Glu) release. We recently showed riluzole prevents acute excitotoxic hippocampal neural injury at 3 days in the kainic acid (KA) model of temporal lobe epilepsy (TLE). Currently, it is unknown if preventing acute neural injury and the neuroinflammatory response is sufficient to suppress epileptogenesis. Methods: The KA rat model of TLE was used to determine if riluzole attenuates acute hippocampal neural injury and reactive gliosis. KA was administered to adult male Sprague-Dawley (250 g) rats at 5 mg/kg/hr until status epilepticus (SE) was …

Periodontal Health In A Large Cohort Of Ugandans Living With Hiv: A Cross-Sectional Study, William Buwembo, Adriane Kamulegeya, Dunstan Kalanzi, Priscilla Naava Namuyonga, Proscovia Nakasujja, David P. Katete, F. Collins Semitala, Catherine Mwesigwa-Lutalo, Samuel Kalungi, Jennifer E. Cameron, Ian G. Munabi

School of Medicine Faculty Publications

Background: The impact of periodontitis on large populations of people living with HIV (PLHIV) in resource-constrained settings remains largely un-investigated. This study aims to address this knowledge gap by providing a comprehensive description of the periodontal health status among a sizable cohort of Ugandans living with HIV. Methods: This was a cross-sectional study with 4,449 participants who were over 18-years old with data captured on their reported age, gender, tobacco use, length of time on HAART and alcohol use. Periodontal health was assessed using the WHO periodontal probe and the modified CPI data entry form. Descriptive statistics were reported using …

Excess Potassium Promotes Autophagy To Maintain The Immunosuppressive Capacity Of Myeloid-Derived Suppressor Cells Independent Of Arginase 1, Ramesh Thylur Puttalingaiah, Matthew J. Dean, Liqin Zheng, Phaethon Philbrook, Dorota Wyczechowska, Timothy Kayes, Luis Del Valle, Denise Danos, Maria Dulfary Sanchez-Pino

School of Medicine Faculty Publications

Potassium ions (K+) are critical electrolytes that regulate multiple functions in immune cells. Recent studies have shown that the elevated concentration of extracellular potassium in the tumor interstitial fluid limits T cell effector function and suppresses the anti-tumor capacity of tumor-associated macrophages (TAMs). The effect of excess potassium on the biology of myeloid-derived suppressor cells (MDSCs), another important immune cell component of the tumor microenvironment (TME), is unknown. Here, we present data showing that increased concentrations of potassium chloride (KCl), as the source of K+ ions, facilitate autophagy by increasing the expression of the autophagosome marker LC3β. Simultaneously, excess potassium …

Sex Hormones And Risk Of Lung And Colorectal Cancers In Women: A Mendelian Randomization Study, Marion Denos, Yi-Qian Sun, Ben Michael Brumpton, Yafang Li, Demetrius Albanes, Andrea Burnett-Hartman, Peter T Campbell, Sébastien Küry, Christopher I Li, Emily White, Jewel N Samadder, Mark A Jenkins, Xiao-Mei Mai

Faculty, Staff and Students Publications

The roles of sex hormones such as estradiol, testosterone, and sex hormone-binding globulin (SHBG) in the etiology of lung and colorectal cancers in women, among the most common cancers after breast cancer, are unclear. This Mendelian randomization (MR) study evaluated such potential causal associations in women of European ancestry. We used summary statistics data from genome-wide association studies on sex hormones and from the Trøndelag Health Study (HUNT) and large consortia on cancers. There was suggestive evidence of 1-standard deviation increase in total testosterone levels being associated with a lower risk of lung non-adenocarcinoma (hazard ratio 0.60, 95% confidence interval …

Tcellsi: A Novel Method For T Cell State Assessment And Its Applications In Immune Environment Prediction, Jing-Min Yang, Nan Zhang, Tao Luo, Mei Yang, Wen-Kang Shen, Zhen-Lin Tan, Yun Xia, Libin Zhang, Xiaobo Zhou, Qian Lei, An-Yuan Guo

Faculty, Staff and Student Publications

T cell is an indispensable component of the immune system and its multifaceted functions are shaped by the distinct T cell types and their various states. Although multiple computational models exist for predicting the abundance of diverse T cell types, tools for assessing their states to characterize their degree of resting, activation, and suppression are lacking. To address this gap, a robust and nuanced scoring tool called T cell state identifier (TCellSI) leveraging Mann-Whitney

Relative Effectiveness And Immunogenicity Of Quadrivalent Recombinant Influenza Vaccine Versus Egg-Based Inactivated Influenza Vaccine Among Adults Aged 18-64 Years: Results And Experience From A Randomized, Double-Blind Trial, Lauren Grant, Jennifer A Whitaker, Sarang K Yoon, Karen Lutrick, Shivam Bhargava, C Perry Brown, Emily Zaragoza, Rebecca V Fink, Jennifer Meece, Kristina Wielgosz, Hana El Sahly, Kurt T Hegmann, Ashley A Lowe, Alia Southworth, Tanya Tatum, Sarah W Ball, Min Z Levine, Matthew S Thiese, Steph Battan-Wraith, John Barnes, Andrew L Phillips, Alicia M Fry, Fatimah S Dawood, Randomized Assessment Of Influenza Vaccine Efficacy Network (Raiven)

Faculty, Staff and Students Publications

BACKGROUND: Immunogenicity studies suggest that recombinant influenza vaccine (RIV) may provide better protection against influenza than standard-dose inactivated influenza vaccines (SD IIV). This randomized trial evaluated the relative vaccine effectiveness (VE) and immunogenicity of RIV versus SD IIV in frontline workers and students aged 18-64 years.

METHODS: Participants were randomized to receive RIV or SD IIV and followed for reverse-transcription polymerase chain reaction (RT-PCR)-confirmed influenza during the 2022-2023 influenza season. Sera were collected from a subset of participants before and at 1 and 6 months postvaccination and tested by hemagglutination inhibition for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria and against cell-grown …

High Fat, High Sucrose Diet Promotes Increased Expression Of Ace2 Receptor In The Siv-Infected Host: Implications For Sars-Cov-2 Infection, Elizabeth C. Delery, Danielle E. Levitt, Angela M. Amedee, Patricia E. Molina, Liz Simon

School of Graduate Studies Faculty Publications

Introduction: People with pre-existing conditions, including metabolic comorbidities, are at greater risk for complications of SARS-CoV-2 infection and expression of machinery required for viral entry into host cells may be a contributing factor. This study tested the hypothesis that high fat, high sucrose diet (HFSD) and alcohol use increase expression of angiotensin converting enzyme 2 (ACE2) receptor and transmembrane serine protease 2 (TMPRSS2) in tissues isolated from simian immunodeficiency virus (SIV) infected macaques, the most clinically relevant model for the study of HIV. Methods: Biospecimens obtained from a longitudinal study of SIV-infected, antiretroviral therapy (ART)-treated female rhesus macaques (Macaca mulatta) …

Creb-Binding Protein/P300 Bromodomain Inhibition Reduces Neutrophil Accumulation And Activates Antitumor Immunity In Triple-Negative Breast Cancer, Xueying Yuan, Xiaoxin Hao, Hilda L Chan, Na Zhao, Diego A Pedroza, Fengshuo Liu, Kang Le, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Michael J Soth, Philip Jones, Xiang Hf Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Tumor-associated neutrophils (TANs) have been shown to promote immunosuppression and tumor progression, and a high TAN frequency predicts poor prognosis in triple-negative breast cancer (TNBC). Dysregulation of CREB-binding protein (CBP)/P300 function has been observed with multiple cancer types. The bromodomain (BRD) of CBP/P300 has been shown to regulate its activity. In this study, we found that IACS-70654, a selective CBP/P300 BRD inhibitor, reduced TANs and inhibited the growth of neutrophil-enriched TNBC models. In the bone marrow, CBP/P300 BRD inhibition reduced the tumor-driven abnormal differentiation and proliferation of neutrophil progenitors. Inhibition of CBP/P300 BRD also stimulated the immune response by inducing …

Exploring New Frontiers In Space Medicine: Unprecedented Detailed Mapping Of Human Biology During Spaceflight, Laura Ioana Patras, Nadia Houerbi, Jankeun Kim

FRONTIERS UNBOUND: Exploring Extreme Environments

No abstract provided.

Targeting Ribosome Biogenesis Is A Novel Approach For The Management Of Pancreatic Cancer, Mudassier Ahmad, Haider Ahsan, Carlos Perez, Muhammad Bangash, Andrew Massey, Emmanuel Anning, Manish Tripathi, Dae Kim, Subhash C. Chauhan, Bilal Bin Hafeez

Research Colloquium

Pancreatic ductal adenocarcinoma is the third leading cause of cancer-related deaths in the United States with limited therapeutic options available. Gemcitabine, a deoxycytidine nucleoside analog is currently considered the most effective therapy for PanCa. However, it shows only a marginal survival benefit of six months. Aberrant ribosome biogenesis occurs in most tumor types. We observed that PanCa cells are addicted to ribosome biogenesis, which supports their highly aggressive metastatic phenotypes. Thus, strategically targeting ribosome biogenesis process could be one of the ideal strategies for the prevention and treatment of PanCa. In this study, we elucidated the molecular mechanisms of POLR1A …

Role Of Poly(A)-Binding Protein Cytoplasmic 1, A Trna-Derived Rna Fragment-Bound Protein, In Respiratory Syncytial Virus Infection, Devin V Davis, Eun-Jin Choi, Deena Ismail, Miranda L Hernandez, Jong Min Choi, Ke Zhang, Kashish Khatkar, Sung Yun Jung, Wenzhe Wu, Xiaoyong Bao

Faculty, Staff and Students Publications

Respiratory Syncytial Virus (RSV) is a significant cause of lower respiratory tract infections (LRTI) across all demographics, with increasing mortality and morbidity among high-risk groups such as infants under two years old, the elderly, and immunocompromised individuals. Although newly approved vaccines and treatments have substantially reduced RSV hospitalizations, accessibility remains limited, and response to treatment varies. This underscores the importance of comprehensive studies on host-RSV interactions. tRNA-derived RNA fragments (tRFs) are recently discovered non-coding RNAs, notable for their regulatory roles in diseases, including viral infections. Our prior work demonstrated that RSV infection induces tRFs, primarily derived from the 5'-end of …