Allergy and Immunology Commons^™

Addressing Barriers In Fair Data Practices For Biomedical Data, Laura D Hughes, Ginger Tsueng, Jack Digiovanna, Thomas D Horvath, Luke V Rasmussen, Tor C Savidge, Thomas Stoeger, Serdar Turkarslan, Qinglong Wu, Chunlei Wu, Andrew I Su, Lars Pache, Niaid Systems Biology Data Dissemination Working Group

Faculty, Staff and Students Publications

No abstract provided.

Developing A Standardized But Extendable Framework To Increase The Findability Of Infectious Disease Datasets, Ginger Tsueng, Marco A Alvarado Cano, José Bento, Candice Czech, Mengjia Kang, Lars Pache, Luke V Rasmussen, Tor C Savidge, Justin Starren, Qinglong Wu, Jiwen Xin, Michael R Yeaman, Xinghua Zhou, Andrew I Su, Chunlei Wu, Liliana Brown, Reed S Shabman, Laura D Hughes

Faculty, Staff and Students Publications

Biomedical datasets are increasing in size, stored in many repositories, and face challenges in FAIRness (findability, accessibility, interoperability, reusability). As a Consortium of infectious disease researchers from 15 Centers, we aim to adopt open science practices to promote transparency, encourage reproducibility, and accelerate research advances through data reuse. To improve FAIRness of our datasets and computational tools, we evaluated metadata standards across established biomedical data repositories. The vast majority do not adhere to a single standard, such as Schema.org, which is widely-adopted by generalist repositories. Consequently, datasets in these repositories are not findable in aggregation projects like Google Dataset Search. …

Macroh2a Histone Variants Modulate Enhancer Activity To Repress Oncogenic Programs And Cellular Reprogramming, Wazim Mohammed Ismail, Amelia Mazzone, Flavia G Ghiraldini, Jagneet Kaur, Manvir Bains, Amik Munankarmy, Monique S Bagwell, Stephanie L Safgren, John Moore-Weiss, Marina Buciuc, Lynzie Shimp, Kelsey A Leach, Luis F Duarte, Chandandeep S Nagi, Saul Carcamo, Chi-Yeh Chung, Dan Hasson, Neda Dadgar, Jian Zhong, Jeong-Heon Lee, Fergus J Couch, Alexander Revzin, Tamas Ordog, Emily Bernstein, Alexandre Gaspar-Maia

Faculty, Staff and Students Publications

Considerable efforts have been made to characterize active enhancer elements, which can be annotated by accessible chromatin and H3 lysine 27 acetylation (H3K27ac). However, apart from poised enhancers that are observed in early stages of development and putative silencers, the functional significance of cis-regulatory elements lacking H3K27ac is poorly understood. Here we show that macroH2A histone variants mark a subset of enhancers in normal and cancer cells, which we coined 'macro-Bound Enhancers', that modulate enhancer activity. We find macroH2A variants localized at enhancer elements that are devoid of H3K27ac in a cell type-specific manner, indicating a role for macroH2A at …

Slo3 In The Fast Lane: The Latest Male Contraceptive Target With A Promising Small-Molecule Inhibitor, Zhi Tan, Thomas X Garcia

Faculty, Staff and Students Publications

No abstract provided.

Antileukemic Properties Of The Kinase Inhibitor Otssp167 In T-Cell Acute Lymphoblastic Leukemia, Cory Seth Bridges, Taylor J Chen, Monica Puppi, Karen R Rabin, H Daniel Lacorazza

Faculty, Staff and Students Publications

Novel drugs are needed to increase treatment response in children with high-risk T-cell acute lymphoblastic leukemia (T-ALL). Following up on our previous report on the activation of the MAP2K7-JNK pathway in pediatric T-ALL, here we demonstrate that OTSSP167, recently shown to inhibit MAP2K7, has antileukemic capacity in T-ALL. OTSSP167 exhibited dose-dependent cytotoxicity against a panel of T-ALL cell lines with IC50 in the nanomolar range (10-50 nM). OTSSP167 induces apoptosis and cell cycle arrest in T-ALL cell lines, associated at least partially with the inhibition of MAP2K7 kinase activity and lower activation of its downstream substrate, JNK. Other leukemic T-cell …

Bnt162b2 Mrna Vaccination Against Coronavirus Disease 2019 Is Associated With A Decreased Likelihood Of Multisystem Inflammatory Syndrome In Children Aged 5-18 Years-United States, July 2021 - April 2022, Laura D Zambrano, Margaret M Newhams, Samantha M Olson, Natasha B Halasa, Ashley M Price, Amber O Orzel, Cameron C Young, Julie A Boom, Leila C Sahni, Aline B Maddux, Katherine E Bline, Satoshi Kamidani, Keiko M Tarquinio, Kathleen Chiotos, Jennifer E Schuster, Melissa L Cullimore, Sabrina M Heidemann, Charlotte V Hobbs, Ryan A Nofziger, Pia S Pannaraj, Melissa A Cameron, Tracie C Walker, Stephanie P Schwartz, Kelly N Michelson, Bria M Coates, Heidi R Flori, Elizabeth H Mack, Laura Smallcomb, Shira J Gertz, Samina S Bhumbra, Tamara T Bradford, Emily R Levy, Michele Kong, Katherine Irby, Natalie Z Cvijanovich, Matt S Zinter, Cindy Bowens, Hillary Crandall, Janet R Hume, Manish M Patel, Angela P Campbell, Adrienne G Randolph, Overcoming Covid-19 Investigators

Faculty, Staff and Students Publications

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), linked to antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with considerable morbidity. Prevention of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) by vaccination might also decrease MIS-C likelihood.

METHODS: In a multicenter, case-control, public health investigation of children ages 5-18 years hospitalized from 1 July 2021 to 7 April 2022, we compared the odds of being fully vaccinated (2 doses of BNT162b2 vaccine ≥28 days before hospital admission) between MIS-C case-patients and hospital-based controls who tested negative for SARS-CoV-2. These associations were examined by age group, timing of vaccination, …

Experiences Of Racism Among Black And African Children With Asthma, Esosa Adah, Rayanna Tucker, Bridgette Jones

Posters

Rationale: The relationship between adverse childhood experiences, toxic stress and asthma risk has been previously described in the literature among adult and pediatric populations. Studies have identified experiences of racism as a chronic stressor associated with asthma morbidity however, most studies have focused primarily on adults or parental perspectives. We initiated a pilot study to characterize described experiences of racism among Black/African American children with persistent asthma and describe some of our initial results. Methods: Children were asked to complete the “Perceptions of Racism in Children and Youth,” a validated questionnaire, measuring perceptions of racism and discrimination. Responses were analyzed …

Maternal Western Diet Is Associated With Distinct Preclinical Pediatric Nafld Phenotypes In Juvenile Nonhuman Primate Offspring, Michael J Nash, Evgenia Dobrinskikh, Rachel C Janssen, Mark A Lovell, Deborah A Schady, Claire Levek, Kenneth L Jones, Angelo D'Alessandro, Paul Kievit, Kjersti M Aagaard, Carrie E Mccurdy, Maureen Gannon, Jacob E Friedman, Stephanie R Wesolowski

Faculty, Staff and Students Publications

Pediatric NAFLD has distinct and variable pathology, yet causation remains unclear. We have shown that maternal Western-style diet (mWSD) compared with maternal chow diet (CD) consumption in nonhuman primates produces hepatic injury and steatosis in fetal offspring. Here, we define the role of mWSD and postweaning Western-style diet (pwWSD) exposures on molecular mechanisms linked to NAFLD development in a cohort of 3-year-old juvenile nonhuman primates offspring exposed to maternal CD or mWSD followed by CD or Western-style diet after weaning. We used histologic, transcriptomic, and metabolomic analyses to identify hepatic pathways regulating NAFLD. Offspring exposed to mWSD showed increased hepatic …

Gut Microbiota And Microbiota-Derived Metabolites Promotes Endometriosis, Sangappa B Chadchan, Sumanta K Naik, Pooja Popli, Chandni Talwar, Satwikreddy Putluri, Chandrasekhar R Ambati, Michael A Lint, Andrew L Kau, Christina L Stallings, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Endometriosis is a pathological condition of the female reproductive tract characterized by the existence of endometrium-like tissue at ectopic sites, affecting 10% of women between the age 15 and 49 in the USA. However, currently there is no reliable non-invasive method to detect the presence of endometriosis without surgery and many women find hormonal therapy and surgery as ineffective in avoiding the recurrences. There is a lack of knowledge on the etiology and the factors that contribute to the development of endometriosis. A growing body of recent evidence suggests an association between gut microbiota and endometriosis pathophysiology. However, the direct …

A Novel Defined Tlr3 Agonist As An Effective Vaccine Adjuvant, Kwang Hyun Ko, Seung Bin Cha, Seung-Hwan Lee, Hyun Shik Bae, Chul Soo Ham, Min-Gyu Lee, Dong-Ho Kim, Seung Hyun Han

Faculty, Staff and Student Publications

Synthetic double-stranded RNA analogs recognized by Toll-like receptor 3 (TLR3) are an attractive adjuvant candidate for vaccines, especially against intracellular pathogens or tumors, because of their ability to enhance T cell and antibody responses. Although poly(I:C) is a representative dsRNA with potent adjuvanticity, its clinical application has been limited due to heterogeneous molecular size, inconsistent activity, poor stability, and toxicity. To overcome these limitations, we developed a novel dsRNA-based TLR3 agonist named NexaVant (NVT) by using PCR-coupled bidirectional in vitro transcription. Agarose gel electrophoresis and reverse phase-HPLC analysis demonstrated that NVT is a single 275-kDa homogeneous molecule. NVT appears to …

Establishing 3d Endometrial Organoids From The Mouse Uterus, Suni Tang, Sydney E Parks, Zian Liao, Dominique I Cope, Sarah E Blutt, Diana Monsivais

Faculty, Staff and Students Publications

Endometrial tissue lines the inner cavity of the uterus and is under the cyclical control of estrogen and progesterone. It is a tissue that is composed of luminal and glandular epithelium, a stromal compartment, a vascular network, and a complex immune cell population. Mouse models have been a powerful tool to study the endometrium, revealing critical mechanisms that control implantation, placentation, and cancer. The recent development of 3D endometrial organoid cultures presents a state-of-the-art model to dissect the signaling pathways that underlie endometrial biology. Establishing endometrial organoids from genetically engineered mouse models, analyzing their transcriptomes, and visualizing their morphology at …

Uncovering The Role Of Cancer Associated Fibroblasts In Tumor Immunosuppression, Kamal Amirneni, Kavitha Yaddanapudi

Posters-at-the-Capitol

Current advances in cancer immunotherapy are hindered by the immunosuppressive nature of the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are a key component of the TME that contribute to suppressing the immune response. Chemokines and cytokines released by CAFs, such as IL-6, attract circulating monocytes which are converted into myeloid-derived suppressor cells (MDSCs). MDSCs suppress T-cells and natural killer cell proliferation which inactivates the immune response and deters immunotherapy. Both Prostaglandin E₂ (PGE₂) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been implicated in the CAF immunosuppressive pathway, but a causal link has yet to be established. We hypothesized …

Increased Camkk2 Expression Is An Adaptive Response That Maintains The Fitness Of Tumor-Infiltrating Natural Killer Cells, Patrick K Juras, Luigi Racioppi, Debarati Mukherjee, Sandeep Artham, Xia Gao, Laura Akullian D'Agostino, Ching-Yi Chang, Donald P Mcdonnell

Faculty, Staff and Students Publications

Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of energy homeostasis in several cell types. Expression of this enzyme in tumor cells promotes proliferation and migration, and expression in tumor-associated immune cells facilitates M2 macrophage polarization and the development of myeloid-derived suppressor cells. Thus, there has been interest in developing CaMKK2 inhibitors as potential anticancer therapeutics. One impediment to clinical development of these agents is that the roles of CaMKK2 in other cellular compartments within the tumor immune microenvironment remain to be established. We report herein that CaMKK2 is expressed at low basal levels in natural killer (NK) …

Leukocytes As Mediators Of Gut-Brain Communication, Dilini Ekanayake

Biomedical Sciences Posters and Presentations

Food allergies

▪ Reactions range from mild/delayed to severe/rapid. ▪ People with mild allergic reactions have increased re-exposure risks. ▪ Cow’s milk allergy tends to manifest with milder allergic reactions.

Cow’s milk allergy (CMA)

▪ CMA has been associated with behavioral and neurological disorders. ▪ How allergic inflammatory signals from the gut reach the brain is unclear

Continuous Consumption Of Whey Protein Affects Motor And Cognitive Functions In A Mouse Model Of Cow’S Milk Hypersensitivity, Geetika Verma

Biomedical Sciences Posters and Presentations

Hypersensitization to a food allergen can occur in the absence of immediate allergic reactions, a condition referred to as asymptomatic sensitization. Using mice asymptomatically sensitized to a bovine whey allergen, β-lactoglobulin (BLG, Bos d 5), we have previously shown that chronic exposure to the allergen results in behavior changes with increased neuroinflammation and cortical demyelination. However, whether allergen avoidance can resolve these pathologies is unknown. Thus, we aimed to compare immunological and behavioral changes in sham- or BLG-sensitized mice with or without the removal of dietary whey after the mice had consumed either a control diet (CTL) or a whey-protein-containing …

Continued Food-Allergen Consumption Exacerbates Beta-Amyloid Accumulation In Allergen-Sensitized Appnl-G-Fmice., Afrina Brishti

Biomedical Sciences Posters and Presentations

Alzheimer’s disease (AD) is the most common neurodegenerative disease, with β-amyloid(Aβ) plaque deposition being one of the hallmark pathologies. However, the etiology of AD remains elusive. While chronic inflammation from recurrent infections or injury seems to contribute to AD development, it is unclear whether atopic diseases, such as allergies, are associated with AD. We previously reported that continuous consumption of a whey protein(WP) -containing diet led to lasting neuro inflammation in C57BL/6J mice that were sensitized but tolerant to a bovine milk allergen, β-lactoglobulin (BLG;Bosd5). Thus, we hypothesized that the persisting neuroinflammation due to repeated allergen consumption would exacerbate AD …

Histamine H3 Receptor Antagonism Mitigates Food-Hypersensitivity-Associated Depressive Behavior And Neuropathology In A Mouse Model Of Cow’S Milk Allergy, Danielle Germundson-Hermanson

Biomedical Sciences Posters and Presentations

Background Histamine is best known for causing allergy symptoms, but it also regulates blood-brain barrier permeability1 and oligodendrocyte differentiation2. Thus, brain histamine levels are tightly controlled.

Previous Findings We demonstrated that histamine and histamine H3 receptor (H3R) levels were elevated in a mouse model of cow’s milk allergy (CMA) in association with intracranial mast cell activation, depression-like behaviors, and cortical demyelination3,4.

Gaps in Knowledge In humans, food allergies are often associated with neuropsychiatric disorders5-7, but the involvement of allergy induced histamine in triggering behavioral changes is unclear.

Hypothesis Repeated allergen consumption can lead to central histaminergic dysfunction through H3R, ultimately …

Continuous Consumption Of Whey Protein Maintains Neuroinflammation In A Mouse Model Of Asymptomatic Cow’S Milk Allergy, Geetika Verma

Biomedical Sciences Posters and Presentations

Using a mouse model of cow’s milk allergy (CMA), we previously showed that C57BL/6J mice sensitized to a bovine whey allergen, β-lactoglobulin (BLG), exhibited anxiety/depression-like behavior and neuroinflammation in the absence of overt anaphylaxis upon allergen exposure

Milk Allergen Increases Intestinal Immune Cells In Association With Neuroinflammation And Behavioral Changes, Dilini Ekanayake

Biomedical Sciences Posters and Presentations

Cow’s milk allergy (CMA)

 CMA h as been associated with neurological disorders.

 How allergic inflammatory signals from the gut reach the brain is unclear.

Repeated Allergen Exposure Induces Histaminergic Dysregulation And Depression-Like Behaviors In A Non-Anaphylactic Food Allergy Mouse Model, Danielle Germundson-Hermanson

Biomedical Sciences Posters and Presentations

▪ Food allergy is often comorbid with neuropsychiatric disorders such as anxiety1,2, depression1,2, OCD3, ADD/ADHD4, and autism5. ➢ The mechanism of how food allergy may impact brain function and behavior in certain allergic individuals has yet to be elucidated.

▪ Mast cells (MCs) are not only the effector cell of the hypersensitivity response but are also important in maintaining brain homeostasis6. ➢ MCs have been implicated in neuropsychiatric and neurodegenerative disorders such as multiple sclerosis7,8.

▪ We have previously found in a mouse model of cow’s milk allergy (CMA) that intracranial MC numbers9 and histamine 3 receptor (H3R)10 increased after …