Medical Specialties Commons^™

Batf2 Is A Glutamine-Responsive Tumour Suppressor Required For Type-I Interferon-Dependent Anti-Tumour Immunity, Wang Gong, Hülya F Taner, Yuesong Wu, Yumin He, Xingwu Zhou, Zaiye Li, Xin Hu, Charisse Ursin, Kala Chand Debnath, Kohei Okuyama, Qiang Hu, Christopher R Donnelly, Felipe Nör, Chamila D Perera, Emily Bellile, Arash Yunesi, Zhiqian Zhai, Mei Zhao, Wanqing Cheng, Zackary R Fitzsimonds, Luke Broses, Jiaqian Li, Shadmehr Demehri, Deepak Nagrath, Gregory T Wolf, Andrew G Sikora, Yanbao Yu, Haitao Wen, Lei Wei, Steven B Chinn, Jeffrey N Myers, Shizuo Akira, Yuying Xie, James J Moon, Yu Leo Lei

Faculty, Staff and Student Publications

Recent evidence highlights the significance of a new type of tumour suppressors, which are not frequently mutated but inhibited by metabolic cues in cancers. Here, we identify BATF2 as a tumour suppressor whose expression is epigenetically silenced by glutamine in Head and Neck Squamous Cell Carcinomas (HNSCC). BATF2 correlates with type-I interferon and Th1 signatures in human HNSCC, with correlation coefficients even stronger than those of the positive control, STING. The phosphorylation of BATF2 at serine 227 promotes the oligomerization of STING. BATF2 deficiency or high glutamine levels result in higher oxygen consumption rates and metabolic profiles unfavorable for …

A Spatiotemporal Model Of Cxcl10 As A Master Regulator Of Immune Evasion And Metastasis In Osteosarcoma, Benjamin B Gyau, Tsz-Kwong Man

Faculty, Staff and Students Publications

The C-X-C motif chemokine ligand 10 (CXCL10) is implicated in the progression of osteosarcoma (OS), the most aggressive pediatric bone malignancy. However, its role often presents a profound clinical paradox: although high circulating levels are strongly linked to poor prognosis, its canonical function is to recruit anti-tumor immune cells. This review unravels these contrasting roles by proposing a novel spatiotemporal model. We argue that in the early stages, immune-evading OS cells initiate the formation of a pre-metastatic niche (PMN) in the lungs, creating a localized inflammatory environment that becomes the primary source of elevated circulating CXCL10. As the disease progresses, …

Amino Acid Signaling In Skeletal Muscle Is Blunted By Prematurity In A Piglet Model, Antonio C Ramos Dos Santos, Agus Suryawan, Ki Beom Jang, Rosemarie D Parada, Mahmoud A Mohammad, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

Background: Preterm (PT) infants are at increased risk for reduced postnatal lean mass accretion. We established that the feeding-induced stimulation of protein synthesis in skeletal muscle is blunted in piglets born PT compared with those born at term.

Objectives: We evaluated the extent to which key components of the amino acid-sensing pathways that regulate mechanistic target of rapamycin complex 1 (mTORC1) activation contribute to anabolic resistance in skeletal muscle of piglets born PT compared with those born term.

Methods: Piglets delivered by cesarean section 10 d PT (n = 23) or at term (n = 22) were administered total parenteral …

Loss Of The Maternal Effect Gene Nlrp2 Impairs Embryonic And Extra-Embryonic Development, Revealing A Novel Genetic Cause Of Congenital Anomalies†, Momal Sharif, Zahra Anvar, Imen Chakchouk, Sara H El-Dessouky, Roni Zemet, Eric C Kao, Wessam E Sharaf-Eldin, Ying-Wooi Wan, Zhandong Liu, Pengfei Liu, Michael Jochum, Ignatia B Van Den Veyver

Duncan NRI Faculty and Staff Publications

Maternal-effect genes (MEGs) play a crucial role in early mammalian development, and their dysfunction can lead to severe embryonic and extra-embryonic abnormalities. NLRP2, a MEG that encodes a subcortical maternal complex (SCMC) protein, has been implicated in preimplantation development, but its role after implantation remains underexplored. In this study, we investigated the developmental consequences of maternal Nlrp2 loss-of-function in a maternal knockout (KO) mouse model at embryonic day 11.5. Embryos derived from Nlrp2-KO females have abnormal yolk sac vasculature, increased embryonic resorption, craniofacial abnormalities, neural tube defects, and congenital heart defects. Placental architecture is disrupted with an altered junctional zone …

Detection Of The Linac Jaw Face Angle Misalignment Using High Energy Electron Beam Symmetry, Song Gao, Andres Cibrian, Jared Ohrt, Peter Balter

Faculty, Staff and Student Publications

Purpose: To demonstrate the usage of a high energy electron beam symmetry measured at different collimator angles to detect jaws face angle misalignments on Varian TrueBeam linear accelerators (linac) during acceptance and commissioning processes.

Methods: During the linac acceptance, all beams were steered to a symmetric shape with the gantry and collimator at 0°. We noted that the symmetries of higher energies electrons (e.g., 16 MeV, 20 MeV) changed over 2% when measured with the collimator at 90° and/or 270° for two linacs commissioned within 5-months of each other. Misaligned applicators were ruled out as the cause of this issue. …

The Impact Of Targeting Traf2 And Nck-Interacting Protein Kinase On Antitumor Effect And Tumor Immune Environment In C-Myc-High Sclc, Azusa Tanimoto, Kavya Ramkumar, C Allison Stewart, Bingnan Zhang, Kyle Concannon, Robert J Cardnell, Li Shen, Qi Wang, Jing Wang, Carl M Gay, Lauren Averett Byers

Faculty, Staff and Student Publications

Introduction: Wnt/β-catenin signaling pathway activation contributes to tumorigenesis and chemo-resistance in SCLC, yet clinical attempts to target this pathway have been unsuccessful. TRAF2 and NCK-interacting protein kinase (TNIK), an essential nuclear activator of Wnt/β-catenin target genes, has not yet been validated as a viable therapeutic target in SCLC. Here, we validated that TNIK inhibition is a promising approach for personalized anticancer therapy in SCLC.

Methods: We correlated the IC50 values of a TNIK inhibitor, NCB-0846, with proteomic profiling (reverse phase protein array) data across 28 SCLC cell lines. Cytokine array analysis was performed to quantify changes in 105 cytokines after …

Anti-Saccade Error Rates Are Associated With Somatic Depressive Symptoms In Cocaine Use Disorder, Constanza De Dios, Heather E Webber, Margaret C Wardle, Jin H Yoon, Michelle A Patriquin, Jessica N Vincent, Joy M Schmitz, Scott D Lane

Faculty, Staff and Student Publications

Background: Inhibitory control deficits are associated with cocaine use disorder (CUD) development and maintenance. Additionally, drug use and inhibitory control can be negatively affected by depressive symptoms, including somatic factors like sleep disturbance and fatigue.

Aim: The current study assessed the relationship between inhibitory control and depressive symptoms among individuals initiating CUD treatment. We examined associations among anti-saccade response inhibition performance, total scores on the Beck Depression Inventory-II (BDI-II), and individual BDI-II items.

Methods: N = 101 patients enrolled in a clinical trial for CUD completed drug-specific anti-saccade and depression (BDI-II) measures prior to treatment. Generalized linear models tested the …

Intraventricular Iron Causes Severe Hydrocephalus – A Model Of Severe Neonatal Hydrocephalus, Kwang-Min Kim, Arokoruba Oboba Cheetham-West, Mohamed Rafiuddin Ahmed, Megan Phillips, Andrey V Malkovskiy, Venkata Raveendra Pothineni, Kyle D Brewer, Chirag B Patel, Jayakumar Rajadas, Kelly B Mahaney

Faculty, Staff and Student Publications

Background: Neonatal germinal matrix hemorrhage-intraventricular hemorrhage and subsequent post-hemorrhagic hydrocephalus (PHH) is a leading cause of neurologic morbidity and mortality in preterm infants. Preclinical models of PHH have implicated hemoglobin and iron-mediated cellular injury in the pathogenesis of PHH, but have typically demonstrated a phenotype characterized by mild to moderate ventriculomegaly – the equivalent of which may not even require intervention in the human condition. We sought to establish a preclinical model of severe IVH that recapitulates the severity of the hydrocephalus phenotype requiring neurosurgical intervention and to determine the causal blood degradation product resulting in severe hydrocephalus following preterm …

Cd177+ Neutrophils: New Drivers Of Liver Regeneration, Yankai Wen, Cynthia Ju

Faculty, Staff and Student Publications

No abstract provided.

Eif3d And Eif3e Mediate Selective Translational Control Of Hypoxia That Can Be Inhibited By Small Molecules, Stephen C Purdy, Kate Matlin, Christopher Alderman, Amber Baldwin, Natasha Shrivastava, Goksu Sarioglu, Somnath Dutta, Kristofor J Webb, Arthur Wolin, Dillon P Boulton, Annika Gustafson, Jyoti Kapali, John D Landua, Michael T Lewis, M Cecilia Caino, James C Costello, William Old, Xiang Wang, Rui Zhao, Heide L Ford, Neelanjan Mukherjee

Faculty, Staff and Students Publications

Exposure to hypoxia is linked to increased cellular plasticity and enhanced metastasis, effects that are primarily attributed to the transcriptional activation of large gene programs downstream of hypoxia-inducible factors (HIFs). However, translational effects in hypoxia, which likely precede transcriptional effects, have remained largely unexplored. Using ribosome profiling, we uncovered a selective translational response in acute hypoxia that is eukaryotic initiation factor (eIF)3d/eIF3e dependent and controls downstream hypoxic responses, including HIF1α accumulation and cellular invasion. We further demonstrated that eIF3e copy number and eIF3e and eIF3d expression signatures are associated with worsened outcomes for patients with breast cancer. Finally, we identified …

Pepquerymhc: Rapid And Comprehensive Tumor Antigen Prioritization From Immunopeptidomics Data, Seunghyuk Choi, Bing Zhang

Faculty, Staff and Students Publications

Determining tumor-specificity of MHC-bound peptides is crucial for cancer immunotherapy development, yet current methods struggle with class II peptides and non-reference sequences. We introduce PepQueryMHC, an ultra-fast tool that integrates MHC-bound peptide sequences with translated RNA-seq reads for efficient tumor antigen prioritization. We demonstrate its versatility in prioritizing class I and II tumor antigens, mapping the cellular origins of presented peptides, and resolving uncertainties surrounding the prevalence of proteasome-spliced peptides.

Sox11 Modulates Bcr Signaling Through The Pax5/Cd19 Axis For Therapeutic Targeting In Btk-Resistant Mantle Cell Lymphoma, Rudra Prasad Dutta, Heng-Huan Lee, Violetta V Leshchenko, Ravi Prakash Shukla, Fangfang Yan, Yang Liu, H Ümit Kaniskan, Xing Qiu, Jian Jin, Lapo Alinari, Michael Wang, Samir Parekh

Faculty, Staff and Student Publications

Mantle cell lymphoma (MCL) is an incurable subtype of B-cell non-Hodgkin lymphoma. Despite multiple approved Bruton tyrosine kinase inhibitors (BTKis), resistance to BTKi continues to pose a major clinical challenge. The transcription factor sex determining region Y-box 11 (SOX11) is expressed in most patients with MCL and is associated with poor outcomes. We have previously demonstrated SOX11-dependent B-cell receptor (BCR) signaling in transgenic models of MCL. Here, we report that SOX11 drives BCR signaling via the transcriptional activation of the PAX5/CD19 axis. The translational potential of these results is significant as single-cell RNA sequencing data show that SOX11 is overexpressed …

Coordinated Changes In Stromal And Hematopoietic Cells That Define The Perinatal To Juvenile Transition In The Mouse Thymus, Anusha Vasudev, Colin R Moore, Aparna Calindi, Seung Woo Kang, Bryan R Helm, Jayashree Srinivasan, Siddhartha Shah, Erin Baker, Ruiting Zong, Nandini Singarapu, Scott Casey, Andrew N Macintyre, Ken S Lau, Laura P Hale, Qi Liu, Nancy R Manley, Lauren I R Ehrlich, Ellen R Richie

Faculty, Staff and Student Publications

Perinatal T cells have distinctive phenotypes and functions that may be due in part to age-associated features of stromal cells in the perinatal thymus. We identify age-associated changes in mouse thymic epithelial cells, mesenchyme, endothelium, and hematopoietic antigen-presenting cells from birth to one month of age using single-cell transcriptional profiling, flow cytometry, and imaging. Coordinated cellular and molecular changes occur at 7-14 days of age, designated "transitional ages," as thymus growth switches to homeostasis. E2F target gene expression declines, and the expression of type I interferon response genes increases across diverse cell types at transitional ages. Alterations in thymic stromal …

Perspectives On The Future Of The Profession Of Microbiology, Todd L Kelson, Heidi B Kaplan, Michelle Dziejman, Shilpa Gadwal, Irene Hulede, Jennifer Bennett, Roger Greenwell, Shelley Payne, Kyle Maclea, Eric Miller, Diana L Vullo, Rebecca Sparks-Thissen, Astral Bertolio, Jorge Cervantes

Faculty, Staff and Student Publications

The Profession of Microbiology (POM) embodies the bulk of the American Society for Microbiology (ASM) members and represents the career preparation arm of the ASM for academia, industry, and clinical lab professions. The ASM Council on Microbial Sciences hosted a virtual retreat in 2025 to identify the future of the POM. The retreat presentations centered on workforce development, professional development, innovations in technology, and interdisciplinary collaborations. Various aspects were identified, such as the need to prepare for careers in industry, as an important goal of future training. It was also clear that scientists, in all walks of life, need professional …

Clair3-Rna: A Deep Learning-Based Small Variant Caller For Long-Read Rna Sequencing Data, Zhenxian Zheng, Xian Yu, Lei Chen, Yan-Lam Lee, Cheng Xin, Angel On Ki Wong, Miten Jain, Rupesh K Kesharwani, Fritz J Sedlazeck, Ruibang Luo

Faculty, Staff and Students Publications

Variant calling with long-read RNA sequencing (lrRNA-seq) helps to analyze full-length isoforms and gene expression but is complicated by high error rates, transcript diversity, RNA editing events, etc. Here, we propose Clair3-RNA, the first deep learning-based variant caller tailored for lrRNA-seq data. Building upon Clair series' pipelines, Clair3-RNA enhances lrRNA-seq variant calling using optimized techniques, such as uneven coverage normalization, refined training data, editing site discovery, and haplotype phasing to enhance performance. Clair3-RNA supports various platforms, including PacBio, ONT complementary DNA sequencing (cDNA), and ONT direct RNA sequencing (dRNA). Clair3-RNA achieved a ~ 91% SNP F1-score on the ONT platform …

Discovery Of Small Molecules And A Druggable Groove That Regulate Dna Binding And Release Of The Ap-1 Transcription Factor Δfosb, Sean Mcneme, Yun Young Yim, Ashwani Kumar, Yi Li, Brandon Hughes, Corey Peyton St Romain, Galina Aglyamova, Jianping Chen, Nghi D Nguyen, Shanghua Fan, Gabriel S Stephens, Wen-Ning Zhao, Samantha Kruzshak, Molly Estill, Corrine Brener, Solange Tofani, Anil Kumar, Earnest P Chen, Nadeen Takatka, Alfred J Robison, Haiying Chen, Reid T Powell, Stephen J Haggarty, Clifford Stephan, Eric J Nestler, Jeannie Chin, Mischa Machius, Jia Zhou, Gabby Rudenko

Faculty, Staff and Students Publications

ΔFOSB, a member of the AP-1 family of transcription factors, mediates long-term neuroadaptations underlying drug addiction, seizure-related cognitive decline, dyskinesias, and several other chronic conditions. AP-1 transcription factors are notoriously difficult to modulate pharmacologically due to the absence of well-defined binding pockets. Here, we identify a novel site on ΔFOSB, located outside the DNA-binding cleft, that accommodates small molecules. We show that sulfonic acid-containing compounds bind to this site via an induced-fit mechanism, reorienting side chains critical for DNA binding, and that they may hinder the ΔFOSB bZIP α-helix from binding to the major groove of DNA. In vivo, direct …

Investigating Chronic Toxicity, Diet, Patient-Reported Outcomes And The Microbiome In Immunotherapy-Treated Metastatic Melanoma Survivors: A New Frontier, Margaux Robert, Satabdi Saha, Nazli Dizman, Michelle Rohlfs, Elizabeth Sirmans, Julie Simon, Rodabe N Amaria, Isabella C Glitza Oliva, Hussein A Tawbi, Michael A Davies, Alexandra Ikeguchi, Karen Basen-Engquist, Keri Schadler, Michael E Roth, Wenye Song, Xiaotao Zhang, Nadim J Ajami, Lorenzo Cohen, Jennifer A Wargo, Christine B Peterson, Jennifer L Mcquade, Carrie R Daniel

Faculty, Staff and Student Publications

Background/Objectives: Immune checkpoint blockade (ICB) therapies have significantly improved outcomes in metastatic melanoma. However, immune-related adverse events (irAEs) and persistent chronic toxicities (CTs) among this emerging survivor population likely influence different facets of quality of life. This study characterized CT, patient-reported outcomes (PROs), diet, physical activity and gut microbiome features in a cohort of long-term survivors with a history of ICB-treated metastatic melanoma.

Methods: Forty-eight patients with a history of metastatic melanoma who initiated ICB treatment at least 3 years earlier and were not currently on treatment were prospectively enrolled from a melanoma survivorship clinic. Participants completed screening …

Epcam Activates The Erk-Egr1 Signaling Axis And Promotes Tnf-Α-Induced The Progression Of Anaplastic Thyroid Cancer, Chi-Chiu Lee, Yi-Jen Su, Sushree Shankar Panda, Chiung-Yi Chiu, Chung-Hsuan Wu, Tsai-Ming Lu, Pi-Chun Li, Yen-Lin Huang, Ruey-Long Hong, Shao-Hsi Hung, Cassian Yee, Stephen Y Lai, Han-Chung Wu

Faculty, Staff and Student Publications

Background: Epithelial cell adhesion molecule (EpCAM) is a pleotropic transmembrane glycoprotein comprising an extracellular domain (EpEX), a single transmembrane domain, and an intracellular domain (EpICD). For several types of cancer, high EpCAM expression is associated with tumor progression, metastasis, immune evasion, and overall poor prognosis. A rare but aggressive form of thyroid cancer, anaplastic thyroid cancer (ATC), has a mean survival time of only 3–6 months after diagnosis.

Methods: The levels of EpEX and EpICD cleavage in clinical patient samples was evaluated by using tissue microarray. Capture enzyme-linked immunosorbent assay (ELISA) was conducted to explore the of shedding EpEX and …

Society For Immunotherapy Of Cancer: Standards For Reporting Of Multiplex Immunohistochemistry/Immunofluorescence Assays (Stormi), Sam Sater, Carlo B Bifulco, Jaime Rodriguez-Canales, Joe Yeong, Guray Akturk, Michael Angelo, Carmen Ballesteros-Merino, Peter Bankhead, Subham Basu, Jorge M Blando, Saska Brajkovic, Marco Cassano, Benjamin J Chen, Ahmet F Coskun, Tricia R Cottrell, Carlos E De Andrea, Robin H Edwards, Colt Egelston, Logan L Engle, Marc S Ernstoff, Rong Fan, Michael Feldman, Bernard A Fox, Jerome Galon, Robyn Gartrell, Sacha Gnjatic, Benjamin F Green, James L Gulley, Anne Hellebust, Stephen Hewitt, Travis J Hollmann, Lucas A Horn, William J Howat, Clifford C Hoyt, Shawn M Jensen, Arutha Kulasinghe, Wiem Lassoued, Steven Lott, James Mansfield, Sebastian Marwitz, George Netto, David B Page, Edwin Parra, David L Rimm, Scott J Rodig, Roberto Salgado, Denis Schapiro, Kurt A Schalper, Joel C Sunshine, Michael J Surace, Alexander S Szalay, Magdalena Thurin, Jose C Villasboas, Keith Wharton, Ignacio I Wistuba, Jennifer H Yearley, Yinyin Yuan, Geroge Zaki, James Ziai, Janis M Taube

Faculty, Staff and Student Publications

Multiplex immunofluorescence and immunohistochemistry (mIF/IHC) are increasingly employed antibody-based technologies that use tissue sparingly and facilitate the detection of co-localized or neighboring biomarkers. Specifically, these platforms enable spatial analyses of the tumor microenvironment as well as extended applications, for example, describing normal tissue anatomy, autoimmunity, infectious diseases, etc. mIF/IHC has greatly enhanced biomarker discovery efforts, and a growing number of studies suggest superiority to traditional IHC. Standardization of staining approaches, reporting of image analysis strategies and resultant data is critical for facilitating cross-study comparisons, validation, deployment, and generalization of findings. To address this challenge, The Society for Immunotherapy of Cancer …

Trait-Like Visual Cortical Hyperactivity In Trait Anxiety, Zhaohan Wu, Yuqi You, Joshua A Brown, Raymond J Dolan, Wen Li

Faculty, Staff and Student Publications

Sensory processing varies across individuals, with some traits-particularly sensory hypersensitivity to basic non-valenced stimuli-linked to emotional traits and psychiatric risk. Traditional accounts attribute this sensory-emotion linkage to limbic or prefrontal modulation, but empirical support is limited. Growing evidence suggests sensory cortex itself flexibly encodes value beyond labeled-line analysis. Across four high-density EEG experiments with multi-wave assessments, we identified reliable visual cortical hyperactivity in high trait anxiety. The effect emerged as early as 46 ms, localized to V1/V2, and was specific to the parvocellular pathway. It was reproducible across arousal states, stimulus valence, extended intervals, and paradigms, and evident for both …

Metabolomic Profiling Reveals Brain Lipid Alterations In Pex7-Deficient Models Of Rhizomelic Chondrodysplasia Punctata, Riya Sankhe, Meredith I Williams, Wedad Fallatah, Laura Mackay, Mary Layne Brown, Pranjali Bhagwat, Sarah H Elsea, Nancy Braverman, Michael F Wangler

Duncan NRI Faculty and Staff Publications

Rhizomelic chondrodysplasia punctata type 1 (RCDP1) is a peroxisomal disorder characterized by skeletal shortening, intellectual disability, seizures, cataracts, and reduced lifespans. RCDP1 is caused by biallelic loss-of-function variants in PEX7, which encodes a protein required for importing select enzymes into the peroxisome matrix, including those essential for ether lipid synthesis (e.g., plasmalogens) and the branched-chain fatty acid catabolism. Plasmalogen deficiency is a hallmark of RCDP1 and other peroxisomal disorders, including RCDP types 2-5 (RCDP2-5) and Zellweger spectrum disorders (ZSD). Here, we performed comprehensive metabolomic profiling of clinical samples from RCDP patients and Pex7-deficient mouse models. We identified profound …

Adaptive Neuromodulation Dialogues: Navigating Current Challenges And Emerging Innovations In Neuromodulation System Development, Frederik Lampert, Matthew R Baker, Michael A Jensen, Amir H Ayyoubi, Christian Bentler, Jessica L Bowersock, Rosana Esteller, Jeffrey A Herron, Graham W Johnson, Daryl R Kipke, Christopher K Kovach, Vaclav Kremen, Filip Mivalt, Joseph S Neimat, Theoden I Netoff, Enrico Opri, Alexander Rockhill, Joshua M Rosenow, Kristin K Sellers, Nathan P Staff, Chandra Prakash Swamy, Ashwin Viswanathan, Gerwin Schalk, Timothy Denison, Dora Hermes, Nuri F Ince, Peter Brunner, Gregory A Worrell, Kai J Miller

Faculty, Staff and Students Publications

Adaptive neuromodulation systems and implantable brain-computer interfaces have made notable strides in recent years, translating experimental prototypes into clinical applications and garnering substantial attention from the public. This surge in interest is accompanied by increased scrutiny related to the safety, efficacy, and ethical implications of these systems, all of which must be directly addressed as we introduce new neurotechnologies. In response, we have synthesized the insights resulting from discussions between groups of experts in the field and summarized them into five key domains essential to therapeutic device development: (1) analyzing current landscape of neuromodulation devices and translational platforms (2) identifying …

Daily Intake Of A Lycopene-Rich Juice Is Associated With Reductions In Inflammatory Markers But Not Increases In Skin Carotenoids In A Pilot Study Among Participants With Obesity, Stephanie B Jilcott Pitts, Qiang Wu, Melissa N Laska, Elizabeth Gates, Megumi H Seese, Katelyn E Senkus, Santiago Carrero Longlax, Alexandra Portillo-Varela, Andrew R Dinardo, Nancy E Moran

Faculty, Staff and Students Publications

Background

Obesity is associated with systemic inflammation, increasing chronic disease risk. Carotenoids possess anti-inflammatory properties, yet the short-term impact of carotenoid-rich juice intake on inflammation in individuals with obesity remains unclear. Therefore, the purpose of this paper was to examine: (1) participant adherence to a 3-week lycopene-rich juice intervention; (2) variance and effect sizes of responses to the dietary intervention; (3) changes in skin and plasma carotenoids, and inflammatory markers among adults with obesity.

Methods

Twenty-five participants with body mass index (BMI) > 30 kg/m2 were recruited and completed the study. Participants drank 4 ounces (118.3 mL) of study-provided tomato juice, …

Life-Threatening Bradycardia In Anti-Nmda-Receptor Encephalitis And A Novel Use For Permanent Pacing, Sarah Tucker, Abhijit Das, Andres Jimenez, Areeba Basit, Yike Jiang, Emily A Smitherman, Heather Van Mater, Taylor Howard, Alexander J Sandweiss, Kristen S Fisher

Faculty, Staff and Students Publications

Background: Pediatric anti-NMDA receptor encephalitis (pNMDARE) is an autoantibody-mediated disorder that can cause severe autonomic dysfunction, including symptomatic bradycardia and asystole. Dysautonomia can last for years, making it very challenging to manage.

Objective: To describe outcomes of 5 pNMDARE patients with life-threatening bradycardic and/or asystolic events who were managed with permanent or semi-permanent pacemaker implantation.

Methods: We performed a retrospective chart review of 5 patients from multiple institutions. We included patients with a diagnosis of pNMDARE (confirmed by positive cerebrospinal fluid and/or serum anti-NMDAR antibodies) who had a permanent or semi-permanent pacemaker placed due to symptomatic bradycardia, sinus pauses, and/or …

Mechanistic And Functional Characterization Of Abtb2 As A Novel Target For Pancreatic Cancer Therapy, Nan Lyu, Olamide T Olaoba, Qiongling Wang, Harinarayanan Janakiraman, Xinjian Liu, Ernest Ramsay Camp, Kun Cheng, Eric T Kimchi, Yi Miao, Kevin F Staveley-O'Carroll, Guangfu Li

Faculty, Staff and Students Publications

BTB/POZ domain-containing proteins are increasingly recognized for their context-dependent roles in cancer, acting as either tumor suppressors or oncogenic drivers depending on the cancer type. Among them, the function of ankyrin repeat and BTB domain-containing protein 2 (ABTB2) in pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy, has remained unexplored. In this study, we employed comprehensive functional genomics approaches—siRNA/shRNA knockdown, CRISPR-Cas9 knockout, plasmid-based overexpression, and a Cre-LoxP transgenic mouse model—to systemically modulate ABTB2 expression in human and murine PDAC cell lines, as well as in the KPC mouse model of PDAC. Our gain- and loss-of-function studies revealed that ABTB2 plays …

Transposable Element-Derived Mir-28-5p And Mir-708-5p: Exploring Potential Roles In Lung Cancer, Sergiu Chira, Cornelia Braicu, Stefan Strilciuc, George A Calin, Ioana Berindan-Neagoe

Faculty, Staff and Student Publications

Background: Transposable elements are normally silenced by epigenetic mechanisms; however, during malignant transformation, epigenetic alterations enable transposons to produce functional molecules like miRNAs. Among these, LINE-2 (L2) elements can generate miRNAs capable of regulating key genes, including tumor suppressors. Two L2-derived miRNAs, miR-28 and miR-708, have been linked to lung cancer, yet the mechanisms underlying their dysregulation remain poorly understood. Our study reveals how genomic context contributes to aberrant gene expression through comprehensive bioinformatic analyses.

Methods: Using bioinformatics analysis, we evaluated the expression of miR-28 and miR-708 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) datasets from TCGA. …

Clinical Practice Variation Among Pediatric Rheumatologists Treating Kawasaki Disease: Results Of A North American Survey, Daniel Ibanez, Bianca Lang, Julia Shalen, Ali Yalcindag, Linda Wagner-Weiner, Kenneth N Schikler, Shoghik Akoghlanian, Hulya Bukulmez, Kristen Hayward, Laura Berbert, Sivia Lapidus, Andrea A Ramirez, Cagri Yildirim-Toruner

Faculty, Staff and Students Publications

Background: The best treatment for children with KD who fail to respond to the first dose of IVIG (refractory KD) is currently unknown. The purpose of this study was to determine treatment practices of pediatric rheumatologists in North America who manage IVIG-refractory KD.

Methods: A 34-item web-based survey was sent to 102 randomly selected members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). The anonymous survey addressed the use of primary intensification as well as the treatment of IVIG-refractory KD.

Results: The response rate was 82%; 56% (all pediatric rheumatologists) completed the survey. Primary intensification was …

Mbnl Loss Of Function In Smooth Muscle As A Model For Myotonic Dystrophy Associated Gastrointestinal Dysmotility, Janel A M Peterson, Jesus A Frias, Andrew N Miller, Krishnakant G Soni, Yi Zhang, Zheng Xia, John W Day, Geoffrey A Preidis, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy and severely affects multiple organ systems, including the brain, heart, skeletal muscle, and gastrointestinal (GI) tract. Despite 80% of individuals with DM1 experiencing GI dysfunction that affects their daily life, the mechanisms of GI dysmotility in DM1 remain an understudied aspect of the disease. DM1 is caused by a CTG repeat expansion in the DMPK gene that, when expressed as an expanded CUG repeat RNA, sequesters and reduces the activity of the muscleblind-like (MBNL) RNA-binding protein family. We developed a mouse line with conditional, smooth muscle-specific knockout of …

Vesicle-Mediated Mitochondrial Clearance Presents An Actionable Metabolic Vulnerability In Triple-Negative Breast Cancer, Jody Vykoukal, Yihui Chen, Mingxin Zuo, Riccardo Ballarò, Monica J Hong, Hansini Krishna, Daniela B Rodriquez-Perera, Hiroyuki Katayama, Ehsan Irajizad, Ranran Wu, Ricardo A León-Letelier, Jennifer B Dennison, Angelica M Gutierrez, Adriana Paulucci-Holthauzen, Timothy C Thompson, Leona Rusling, Yining Cai, Fu Chung Hsiao, Soyoung Park, Banu Arun, Samir Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

Selective autophagy of mitochondria is known to promote cancer cell survival and progression, including in triple-negative breast cancer (TNBC). Here, we apply an integrated multi-omics approach together with functional experimental analyses to investigate metabolic adaptations that support mitochondrial quality control in TNBC. We detail a mitochondrial quality control mechanism, complementary to mitophagy, that is enabled by a program of heightened extracellular sphingomyelin salvaging in TNBC coupled with extracellular vesicle-mediated intracellular clearance of mitochondrial damage. Targeting of this onco-metabolic pathway via repurposing of eliglustat, a selective small molecule inhibitor of glucosylceramide synthase, results in ceramide-mediated compensatory mitophagy and cancer cell death …

Accurate Imputation Of Pathway-Specific Gene Expression In Spatial Transcriptomics With Pasta, Ruoxing Li, Peng Yang, Mauro Di Pilato, Jianjun Zhang, Christopher R Flowers, Lulu Shang, Ziyi Li

Faculty, Staff and Student Publications

Mapping the entire transcriptome at single-cell resolution under its natural spatial context is essential for investigating the oncogenesis and progression of diseases. The recently emerged targeted in-situ technologies retain the spatial organization of cells at high resolution, although they remain limited in the number of genes that can be simultaneously measured. To overcome this obstacle, numerous computational methods have been developed to predict unmeasured gene expression in spatial transcriptomics data by leveraging scRNA-seq data. Most of these methods focus on the expression of individual genes and usually generate highly variable predictions. In this study, we introduce PASTA (PAthway-oriented Spatial gene …