Digital Commons Network^™

The Lung Cancer Autochthonous Model Gene Expression Database Enables Cross-Study Comparisons Of The Transcriptomic Landscapes Across Mouse Models, Ling Cai, Fangjiang Wu, Qinbo Zhou, Ying Gao, Bo Yao, Ralph J Deberardinis, George K Acquaah-Mensah, Vassilis Aidinis, Jennifer E Beane, Shyam Biswal, Ting Chen, Carla P Concepcion-Crisol, Barbara M Grüner, Deshui Jia, Robert A Jones, Jonathan M Kurie, Min Gyu Lee, Per Lindahl, Yonathan Lissanu, Corina Lorz, David Macpherson, Rosanna Martinelli, Pawel K Mazur, Sarah A Mazzilli, Shinji Mii, Herwig P Moll, Roger A Moorehead, Edward E Morrisey, Sheng Rong Ng, Matthew G Oser, Arun R Pandiri, Charles A Powell, Giorgio Ramadori, Mirentxu Santos, Eric L Snyder, Rocio Sotillo, Kang-Yi Su, Tetsuro Taki, Kekoa Taparra, Phuoc T Tran, Yifeng Xia, J Edward Van Veen, Monte M Winslow, Guanghua Xiao, Charles M Rudin, Trudy G Oliver, Yang Xie, John D Minna

Faculty, Staff and Student Publications

Lung cancer, the leading cause of cancer mortality, exhibits diverse histological subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. In this study, we established the Lung Cancer Autochthonous Model Gene Expression Database (LCAMGDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMMs), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model. Meticulous curation and collaboration with data depositors produced a robust and comprehensive database, …

G-Quadruplex Stabilizer Cx-5461 Effectively Combines With Radiotherapy To Target Α-Thalassemia/Mental Retardation X-Linked-Deficient Malignant Glioma, Sharvari Dharmaiah, Prit Benny Malgulwar, William E Johnson, Brandon A Chen, Vladislav Sharin, Benjamin T Whitfield, Christian Alvarez, Vasudev Tadimeti, Ahsan S Farooqi, Jason T Huse

Faculty, Staff and Student Publications

Background: Inactivation of α-thalassemia/mental retardation X-linked (ATRX) represents a defining molecular feature in large subsets of malignant glioma. ATRX deficiency gives rise to abnormal G-quadruplex (G4) DNA secondary structures, enhancing replication stress and genomic instability. Building on earlier work, we evaluated the extent to which pharmacological G4 stabilization selectively enhances DNA damage and cell death in ATRX-deficient preclinical glioma models.

Methods: Using the G4 stabilizer CX-5461, we treated patient-derived glioma stem cells (GSCs) in vitro and GSC flank and intracranial murine xenografts in vivo to evaluate efficacy as both a single agent and in combination with ionizing radiation (IR), the …

Label-Free Multimodal Optical Biopsy Reveals Biomolecular And Morphological Features Of Diabetic Kidney Tissue In 2d And 3d, Anthony A Fung, Zhi Li, Craig Boote, Petar Markov, Joseph P Gaut, Sanjay Jain, Lingyan Shi

2020-Current year OA Pubs

Kidney disease, the ninth leading cause of death in the United States, suffers from poor diagnostic efficiency (10%). Traditional biopsies use molecular reagents to enhance diagnostic power but are limited by overlapping spatial and chromatic signals, product quality variability, and additional processing. To address these challenges without disrupting routine diagnostics, we implement label-free imaging modalities-stimulated Raman scattering (SRS), second harmonic generation (SHG), and two-photon fluorescence (TPF)-within a single setup. We identify morphological, lipidomic, and metabolic biomarkers in control and diabetic kidney samples at subcellular resolution. Label-free Stimulated Raman Histology (SRH) reveals distinct collagen morphology, mesangial-glomerular volumes, lipid saturation, redox status, …

Meningeal Lymphatics-Microglia Axis Regulates Synaptic Physiology, Kyungdeok Kim, Daviti Abramishvili, Siling Du, Zachary Papadopoulos, Jay Cao, Jasmin Herz, Igor Smirnov, Jean-Leon Thomas, Marco Colonna, Jonathan Kipnis

2020-Current year OA Pubs

Meningeal lymphatics serve as an outlet for cerebrospinal fluid, and their dysfunction is associated with various neurodegenerative conditions. Previous studies have demonstrated that dysfunctional meningeal lymphatics evoke behavioral changes, but the neural mechanisms underlying these changes have remained elusive. Here, we show that prolonged impairment of meningeal lymphatics alters the balance of cortical excitatory and inhibitory synaptic inputs, accompanied by deficits in memory tasks. These synaptic and behavioral alterations induced by lymphatic dysfunction are mediated by microglia, leading to increased expression of the interleukin 6 gene (Il6). IL-6 drives inhibitory synapse phenotypes via a combination of trans- and classical IL-6 …

Acute Kidney Injury Triggers Hypoxemia By Lung Intravascular Neutrophil Retention That Reduces Capillary Blood Flow, Yohei Komaru, Liang Ning, Carine Lama, Anusha Suresh, Eirini Kefaloyianni, Mark J. Miller, Shinichi Kawana, Hailey M Shepherd, Wenjun Li, Daniel Kreisel, Andreas Herrlich

2020-Current year OA Pubs

Sterile acute kidney injury (AKI) is common in the clinic and frequently associated with unexplained hypoxemia that does not improve with dialysis. AKI induces remote lung inflammation with neutrophil recruitment in mice and humans, but which cellular cues establish neutrophilic inflammation and how it contributes to hypoxemia is not known. Here we report that AKI induced rapid intravascular neutrophil retention in lung alveolar capillaries without extravasation into tissue or alveoli, causing hypoxemia by reducing lung capillary blood flow in the absence of substantial lung interstitial or alveolar edema. In contrast to direct ischemic lung injury, lung neutrophil recruitment during remote …

Maintenance Of Graft Tissue-Resident Foxp3+ Cells Is Necessary For Lung Transplant Tolerance In Mice, Wenjun Li, Yuriko Terada, Yun Zhu Bai, Yuhei Yokoyama, Hailey M. Shepherd, Junedh M. Amrute, Amit I. Bery, Zhiyi Liu, Jason M. Gauthier, Marina Terekhova, Jon H. Ritter, Varun Puri, Ramsey R. Hachem, Maxim N. Artyomov, Kory J. Lavine, Ruben G. Nava, Andrew E. Gelman, Daniel Kreisel, Et Al.

2020-Current year OA Pubs

Mechanisms that mediate allograft tolerance differ between organs. We have previously shown that Foxp3+ T cell-enriched bronchus-associated lymphoid tissue (BALT) is induced in tolerant murine lung allografts and that these Foxp3+ cells suppress alloimmune responses locally and systemically. Here, we demonstrated that Foxp3+ cells that reside in tolerant lung allografts differed phenotypically and transcriptionally from those in the periphery and were clonally expanded. Using a mouse lung retransplant model, we showed that recipient Foxp3+ cells were continuously recruited to the BALT within tolerant allografts. We identified distinguishing features of graft-resident and newly recruited Foxp3+ cells and showed that graft-infiltrating Foxp3+ …

Modulation Of Her2 Internalization Enhances Single-Dose Antibody-Drug Potency In Her2+ Gastric Cancer, Abbey Zidel, Alex Benton, Emma Brown, Shayla Shmuel, Alex Vanover, Sandeep Surendra Panikar, Ron Bose, Haeseong Park, Andrew A Davis, Patrícia M R Pereira

2020-Current year OA Pubs

HER2 is a membrane receptor tyrosine kinase overexpressed in 18-20% of gastric tumors. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) that targets HER2-positive (HER2

Multifaceted Roles Of Epac Signaling In Renal Functions, Oleh Pochynyuk, Kyrylo Pyrshev, Xiaodong Cheng

The Brown Foundation: Institute of Molecular Medicine

3',5'-cyclic adenosine monophosphate (cAMP) is a fundamental secondary messenger capable of rapidly amplifying and propagating cellular signals in response to various extracellular stimuli. cAMP plays a significant role in hormone-mediated regulation of renal fluid and electrolyte balance. Impaired signaling of cAMP has been linked to a variety of pathological ramifications in the kidneys. This review explores the physiological functions of exchange proteins directly activated by cAMP (Epac) in renal water balance and the regulation of solute transport in the renal tubule. Additionally, the involvement of Epac signaling in renal pathologies such as acute kidney injury, chronic kidney disease, and polycystic …

Immunotherapy With Nebulized Pattern Recognition Receptor Agonists Restores Severe Immune Paralysis And Improves Outcomes In Mice With Influenza-Associated Pulmonary Aspergillosis, Jezreel Pantaleón García, Sebastian Wurster, Nathaniel D Albert, Uddalak Bharadwaj, Keerthi Bhoda, Vikram K Kulkarni, Mbaya Ntita, Paris Rodríguez Carstens, Madeleine Burch-Eapen, Daniela Covarrubias López, Jania Foncerrada Lizaola, Katherine E Larsen, Lauren M Matula, Seyed J Moghaddam, Yongxing Wang, Dimitrios P Kontoyiannis, Scott E Evans

Faculty, Staff and Student Publications

Influenza-associated pulmonary aspergillosis (IAPA) is a potentially deadly superinfection in patients with influenza pneumonia, especially those with severe disease, underlying immunosuppression, corticosteroid therapy, or requiring intensive care support. Given the high mortality of IAPA, adjunct immunomodulatory strategies remain a critical unmet need. Previously, the desensitization of pattern recognition pathways has been described as a hallmark of IAPA pathogenesis and a predictor of mortality in IAPA patients. Therefore, we studied the impact of nebulized Toll-like receptor 2/6/9 agonists Pam2 CSK4 (Pam2) and CpG oligodeoxynucleotides (ODNs) on infection outcomes and pulmonary immunopathology in a corticosteroid-immunosuppressed murine IAPA model. Mice with IAPA receiving …

Forward Genetic Screen In Zebrafish Identifies New Fungal Regulators That Limit Host-Protective Candida-Innate Immune Interaction, Bailey A Blair, Emma Bragdon, Gursimran Dhillon, Nnamdi Baker, Lena Stasiak, Mya Muthig, Pedro Miramon, Michael C Lorenz, Robert T Wheeler

Faculty, Staff and Student Publications

Candida is one of the most frequent causes of bloodstream infections, and our first line of defense against these invasive infections is the innate immune system. The early immune response is critical in controlling Candida albicans infection, but C. albicans has several strategies to evade host immune attack. Phagocytosis of C. albicans blocks hyphal growth, limiting host damage and virulence, but how C. albicans limits early recruitment and phagocytosis in vertebrate infection is poorly understood. To study innate immune evasion by intravital imaging, we utilized the transparent larval zebrafish infection model to screen 131 C. albicans mutants for altered …

Theta Oscillons In Behaving Rats, M S Zobaer, Nastaran Lotfi, Carli M Domenico, Clarissa Hoffman, Luca Perotti, Daoyun Ji, Yuri Dabaghian

Faculty, Staff and Students Publications

Recently discovered constituents of the brain waves—the oscillons—provide a high-resolution representation of the extracellular field dynamics. Here, we study the most robust, highest-amplitude oscillons recorded in actively behaving male rats, which underlie the traditional θ-waves. The resemblances between θ-oscillons and the conventional θ-waves are manifested primarily at the ballpark level—mean frequencies, mean amplitudes, and bandwidths. In addition, both hippocampal and cortical oscillons exhibit a number of intricate, behavior-attuned, transient properties that suggest a new vantage point for understanding the θ-rhythms’ structure, origins and functions. In particular, we demonstrate that oscillons are frequency-modulated waves, with speed-controlled …

A Role For Δ Subunit-Containing Gabaa Receptors On Parvalbumin-Positive Neurons In Maintaining Electrocortical Signatures Of Sleep States, Peter M Lambert, Sofia V Salvatore, Xinguo Lu, Hong-Jin Shu, Ann Benz, Nicholas Rensing, Carla M Yuede, Michael Wong, Charles F Zorumski, Steven Mennerick

2020-Current year OA Pubs

GABA

Genome-Wide Allele-Specific Expression In Multi-Tissue Samples From Healthy Male Baboons Reveals The Transcriptional Complexity Of Mammals, Ramesh Ramasamy, Muthuswamy Raveendran, R Alan Harris, Hiep D Le, Ludovic S Mure, Giorgia Benegiamo, Ouria Dkhissi-Benyahya, Howard Cooper, Jeffrey Rogers, Satchidananda Panda

Faculty, Staff and Students Publications

Allele-specific expression (ASE) is pivotal in understanding the genetic underpinnings of phenotypic variation within species, differences in disease susceptibility, and responses to environmental factors. We processed 11 different tissue types collected from 12 age-matched healthy olive baboons (Papio anubis) for genome-wide ASE analysis. By sequencing their genomes at a minimum depth of 30×, we identified over 16 million single-nucleotide variants (SNVs). We also generated long-read sequencing data, enabling the phasing of all variants present within the coding regions of 96.5% of assayable protein-coding genes as a single haplotype block. Given the extensive heterozygosity of baboons relative to humans, we could …

Intraspecific Sensory Diversity And The Decapod Claw: Patterns Of Sensillation Are Heterochelic And Sexually Dimorphic In Pagurus Bernhardus, Ari Drummond, Summer Nash, Tianna Holloway, Alexander Wilson, Lucy Turner, Mark Briffa, David T Bilton

School of Biological and Marine Sciences

Information detection affects physiological performance and behaviour and is vital to survival and fitness. Despite the recognised importance of sensory adaptations in information acquisition and manipulation, many forms of sensory variation—from within individuals to between species—remain underexplored. To better understand the role of information in evolution, it is important to examine sensory variation as part of a cohesive framework of sensory diversity. Using the decapod claw, a structure well-recognised for its morphological variation, we investigated sensory diversity at the intraspecific level by assessing heterochely and sexual dimorphism in the chelar morphologies of Pagurus bernhardus hermit crabs. We employed a novel …

Smooth Muscle Cells And Fibroblasts In The Ascending Aorta Exhibit Minor Differences Between Embryonic Origins In Angiotensin Ii-Driven Transcriptional Alterations, Sohei Ito, David B Graf, Yuriko Katsumata, Jessica J Moorleghen, Chen Zhang, Yanming Li, Scott A Lemaire, Ying H Shen, Hong S Lu, Alan Daugherty, Hisashi Sawada

Faculty, Staff and Students Publications

Thoracic aortopathy is influenced by angiotensin II (AngII) and exhibits regional heterogeneity with the ascending aorta being particularly susceptible. In this region, smooth muscle cells (SMCs) and selected fibroblasts originate from the second heart field (SHF) and cardiac neural crest (CNC). While our previous study revealed a critical role of SHF-derived cells in AngII-mediated aortopathy, the contribution of CNC-derived cells remains unclear. To investigate lineage-specific responses to AngII, Mef2c-Cre R26RmT/mG mice were infused with AngII. Ascending aortas were harvested at baseline or after 3 days of infusion, representing the prepathological phase. Cells were sorted based on their embryonic origins and …

Ogg1s326c Variant Frequent In Human Populations Facilitates Inflammatory Responses Due To Its Extended Interaction With Dna Substrate, Jinling Han, Meichen Zhang, Jiakun Ge, Zhihua Ji, Jianyi Zhao, Yinchao Hu, Chunshuang Li, Yaoyao Xue, Xining Li, Haiwang Zhao, Zixu Cui, Miaomiao Tian, Xu Zheng, Dapeng Wang, Jing Wang, Min Wei, Zsolt Radak, Yusaku Nakabeppu, Istvan Boldogh, Xueqing Ba

Faculty, Staff and Student Publications

8-oxoguanine (8-oxoGua) is one of the most frequent forms of oxidative DNA base lesions, repaired by 8-oxoguanine DNA glycosylase 1 (OGG1) via base excision repair (BER) pathway to maintain genome fidelity. The human allelic variant hOGG1^S326C, prevalent in Caucasians and Asians, has been regarded as a susceptibility factor for various diseases, yet its pathogenic mechanism remains elusive. In this study, we demonstrate that Ogg1^S326C/S326C mice exhibit increased and sustained airway inflammation compared with wild-type (WT) Ogg1^S326/S326 mice. Mechanistically, in response to inflammatory stimulation, OGG1S326C undergoes reactive oxygen species-induced dimerization, which impairs its base excision function, but …

Dnmt3a Regulates Murine Megakaryocyte-Biased Hematopoietic Stem Cell Fate Decisions, Sarah M Waldvogel, Virginia Camacho, Dandan Fan, Anna G Guzman, Alejandra Garcia-Martell, Elmira Khabusheva, Jacey Rodriguez Pridgen, Josephine De La Fuente, Rachel Rau, Ashlyn G Laidman, Maria N Barrachina, Estelle Carminita, Justin A Courson, Michael R Williamson, Joanne I Hsu, Chun-Wei Chen, Jaime Reyes, Subhashree Pradhan, Rolando E Rumbaut, Alan R Burns, Benjamin Deneen, Jianzhong Su, Kellie R Machlus, Margaret A Goodell

Center on Aging Staff Publications

Hematopoietic stem cells (HSCs) are defined by their capacity to regenerate all main components of peripheral blood, but individual HSCs exhibit a range of preferences for generating downstream cell types. Their propensities are thought to be epigenetically encoded, but few differential regulatory mechanisms have been identified. In this work, we explored the role of DNA methyltransferase 3A (DNMT3A) in the megakaryocyte-biased HSC population, which is thought to reside at the top of the hematopoietic hierarchy. We demonstrate that heterozygous loss of DNMT3A (Dnmt3a+/-) in these megakaryocyte-biased HSCs has distinct consequences compared with the rest of the HSC pool. These megakaryocyte-biased …

Loss Of Progesterone Receptor In Smooth Muscle Cells Has No Impact On Oviductal Contractions And Preimplantation Embryo Development†, Emily A Mcglade, Jiude Mao, Kalli K Stephens, Cayce N Rose, John P Lydon, Wipawee Winuthayanon

Faculty, Staff and Students Publications

No abstract provided.

Disruption Of Oocyte Sumoylation Impacts Critical Regulatory Processes During Folliculogenesis In Mice, Zian Liao, Tessa E Steenwinkel, Bruno Moscoso, Ernesto Salas, Bethany K Patton, Amanda Rodriguez, Anna Malovannaya, Stephanie A Pangas

Faculty, Staff and Students Publications

The conjugation of small ubiquitin-like modifiers (SUMO) to target proteins, known as SUMOylation, plays a crucial role in regulating protein homeostasis, activity, interaction with other proteins, and subcellular localization. Loss of SUMOylation in nongrowing oocytes by conditional deletion of the E2 SUMO conjugating enzyme, Ube2i, at the primordial follicle stage leads to female sterility due to complex changes in oocyte development, including altered folliculogenesis, defective meiotic progression, and premature loss of the ovarian reserve. In this study, proteomics was used to compare control and Ube2i conditional knockout ovaries during the first wave of folliculogenesis to identify key differences that may …

Temporal Regulation Of Early-Stage Cytokine Expression In Diabetic Wound Healing Under Negative Pressure Wound Therapy, Hua-Sheng Chiu, Ting-Shuo Huang, Chien-Tzung Chen, Xin-Yu Lin, Po-Cheng Liao, Cai-Cin Liou, Chih-Chin Hsu, Sonal Somvanshi, Pavel Sumazin, Pang-Hung Hsu, Chi-Chin Sun, Yu-Chiau Shyu

Faculty, Staff and Students Publications

Negative pressure wound therapy (NPWT) is widely recognized for its efficacy in treating diabetic wounds, but the mechanisms involved in the wound healing process remain unclear. By examining changes in blood cytokine levels as molecular signaling precursors, we aim to provide a comprehensive cytokine profile to support adjunctive therapy research and clinical applications. A diabetic mouse wound model was established to compare cytokine profiles between NPWT-treated and standard dressing groups, identifying key signaling candidates that may facilitate wound healing. By integrating normal mouse data with large-scale cytokine analysis, we developed a time-stratified NPWT approach to track acute-phase cytokine fluctuations in …

Molecular Basis Of Trpv3 Channel Blockade By Intracellular Polyamines, Jingying Zhang, Peng Yuan, Colin G Nichols, Grigory Maksaev

2020-Current year OA Pubs

ThermoTRPV1-4 channels are involved in the regulation of multiple physiological processes, including thermo- and pain perception, thermoregulation, itch, and nociception and therefore tight control of their activity is a critical requirement for correct perception of noxious stimuli and pain. We previously reported a voltage-dependent inhibition of TRPV1-4 channels by intracellular polyamines that could be explained by high affinity spermine binding in, and passage through, the permeation path. Here, using electrophysiology and cryo-electron microscopy, we elucidate molecular details of TRPV3 blockade by endogenous spermine and its analog NASPM. We identify a high-affinity polyamine interaction site at the intracellular side of the …

Let-7 Restrains An Epigenetic Circuit In At2 Cells To Prevent Fibrogenic Intermediates In Pulmonary Fibrosis, Matthew J Seasock, Md Shafiquzzaman, Maria E Ruiz-Echartea, Rupa S Kanchi, Brandon T Tran, Lukas M Simon, Matthew D Meyer, Phillip A Erice, Shivani L Lotlikar, Stephanie C Wenlock, Scott A Ochsner, Anton Enright, Alex F Carisey, Freddy Romero, Ivan O Rosas, Katherine Y King, Neil J Mckenna, Cristian Coarfa, Antony Rodriguez

Faculty, Staff and Students Publications

MicroRNA-mediated post-transcriptional regulation of lung alveolar type 2 (AT2) and AT1 cell differentiation remains understudied. Here, we demonstrate that the let-7 miRNA family plays a homeostatic role in AT2 quiescence by preventing the uncontrolled accumulation of AT2 transitional cells and promoting AT1 differentiation. Using mouse and organoid models, we show that genetic ablation of let-7a1/let-7f1/let-7d cluster (let-7afd) in AT2 cells prevents AT1 differentiation and leads to KRT8 transitional cell accumulation in progressive pulmonary fibrosis. Integration of AGO2-eCLIP with RNA-sequencing identified direct let-7 targets within an oncogene feed-forward regulatory network, including BACH1/EZH2/MYC, which drives an aberrant fibrotic cascade. Additional CUT&RUN-sequencing analyses …

Multi-Parametric Quantitative Evaluation Of Murine Cervical Remodeling During Pregnancy And Postpartum, Yan Yan, Jose Galaz, Joshua Marvald, Tanzy Love, Steven Yellon, Nardhy Gomez-Lopez, Mohammad Mehrmohammadi

2020-Current year OA Pubs

Cervical remodeling during pregnancy is a critical process that, if untimely, can lead to complications such as preterm birth (PTB). This study introduces a novel multi-parametric approach combining non-invasive imaging modalities to quantify cervical tissue changes during pregnancy and postpartum in a murine model. By integrating ultrasound-based measurements of cervical length, photoacoustic imaging of the collagen-to-water ratio, and elastography for tissue elasticity alongside histological assessments, this method provides a comprehensive evaluation of cervical remodeling. The findings reveal that combining these parameters significantly improves the accuracy of gestational age prediction compared to individual measurements, with a tri-parametric model achieving 85.3% prediction …

Optimizing Peptide Nucleic Acid-Based Pretargeting For Enhanced Targeted Radionuclide Therapy, Mohamed Altai, Ábel Nagy, Pauline Granit, Wahed Zedan, Myriam Cerezo-Magaña, Julie Park, Katharina Lückerath, Susanne Geres, Marie Sydoff, Daniel L J Thorek, Kristina Westerlund, David Ulmert, Amelie Eriksson Karlström

2020-Current year OA Pubs

Radiolabeled targeting agents have emerged as valuable tools for the treatment of disseminated cancer. Monoclonal antibodies (mAbs) are widely employed as carriers for diagnostic and therapeutic radionuclides due to their exceptional specificity and affinity. However, their prolonged circulatory half-life can diminish diagnostic efficacy and increase radiation exposure to non-target tissues in therapeutic applications, resulting in dose-limiting toxicities. To overcome this limitation, pretargeting technologies emerge as promising strategies to enhance tumor-to-background ratio and reduce radiation exposure of healthy tissues. Our previous work introduced a pretargeting concept leveraging the specific interaction between two peptide nucleic acid (PNA) probes, HP1 and HP2, as …

High-Throughput Echocardiography-Guided Induction Of Myocardial Ischemia/Reperfusion In Mice., Florian Sicklinger, Niklas Hartmann, Attila Kovacs, Carla Weinheimer, Jess Nigro, Tobias Thiemann, Junedh M Amrute, David Schumacher, Moritz P Kornadt, Laura M Wienecke, Lennart Rompel, Johannes Fischer, John F Bachman, Olivia Bedard, Shibali Das, Tim C Kuhn, Mirko Völkers, Ralf P Brandes, Rafael Kramann, Nadia Rosenthal, Norbert Frey, Kory J Lavine, Florian Leuschner

Faculty Research 2025

BACKGROUND: Mouse models of myocardial ischemia with subsequent heart failure are common approaches to examine heart failure pathology and possible treatment strategies. We sought to establish a high-throughput approach for echocardiography-guided induction of myocardial ischemia/reperfusion (IR) in mice.

METHODS: After visualization of the left coronary artery with high-resolution ultrasound imaging and echocardiographic definition of the level of coronary occlusion, the left anterior descending artery was temporarily occluded with 2 micromanipulator-controlled needles. Functional and molecular changes were assessed and compared with commonly performed surgical techniques.

RESULTS: Echocardiography-guided induction of myocardial IR enabled standardized induction of myocardial IR injury with subsequent left …

Three Cases Of Adolescent Orf Virus Skin And Soft Tissue Infection In Southeast Texas, Margaret Taylor Danner, Caroline A Schrodt, Alexandra Tuttle, Victoria Shelus, Brendan Sullivan, Ankhi Dutta, Claire Bocchini, Denver Niles

Faculty, Staff and Students Publications

We report 3 adolescents who presented to a tertiary care hospital in Houston, Texas, with cutaneous skin lesions after contact with sheep and/or goats. The cases presented a diagnostic challenge initially but were later suspected or confirmed as orf virus infection after consultation with infectious diseases specialists.

High-Throughput Echocardiography-Guided Induction Of Myocardial Ischemia/Reperfusion In Mice, Florian Sicklinger, Niklas Hartmann, Attila Kovacs, Carla Weinheimer, Jess Nigro, Junedh M. Amrute, Kory J. Lavine, Et Al.

2020-Current year OA Pubs

BACKGROUND: Mouse models of myocardial ischemia with subsequent heart failure are common approaches to examine heart failure pathology and possible treatment strategies. We sought to establish a high-throughput approach for echocardiography-guided induction of myocardial ischemia/reperfusion (IR) in mice.

METHODS: After visualization of the left coronary artery with high-resolution ultrasound imaging and echocardiographic definition of the level of coronary occlusion, the left anterior descending artery was temporarily occluded with 2 micromanipulator-controlled needles. Functional and molecular changes were assessed and compared with commonly performed surgical techniques.

RESULTS: Echocardiography-guided induction of myocardial IR enabled standardized induction of myocardial IR injury with subsequent left …

Hippocampal-Prefrontal Functional Neural Networks In A Rat Model Of Fragile X Syndrome Are Poorly Organized With Limited Resiliency., Mohamed Ouardouz, Patrick Jasinski, Mohamed Khalife, J Matthew Mahoney, Amanda E Hernan, Rod C Scott

Faculty Research 2025

Fragile X Syndrome (FXS) is a common cause of autism spectrum symptoms. The genetic mutation results in multiple molecular alterations that are hypothesized to negatively impact neural circuit development although the nature of any functional neural dynamic consequences remain unclear. Therefore, the characteristics of hippocampal-prefrontal (H-PFC) network dysfunction were investigated in a rat model of FXS. FMR-KO and control rats underwent behavioral tests assessing sociability, memory, and anxiety to validate and replicate previously recognized deficits. Single-unit electrophysiology in the H-PFC circuit during exploration was used to measure patterns of action potential firing that were then compared between groups using generalized …

Sirt6 Deficiency Promotes Senescence And Age-Associated Intervertebral Disc Degeneration In Mice, Pranay Ramteke, Bahiyah Watson, Mallory Toci, Victoria Tran, Shira N Johnston, Maria Tsingas, Ruteja Barve, Ramkrishna Mitra, Richard Loeser, John Collins, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain. While the etiological factors for disc degeneration vary, age is still one of the most important risk factors. Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health, however its role in the intervertebral disc health remains unexplored. We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc (Acan^CreERT2; Sirt6^fl/fl). Histological studies showed a degenerative phenotype in knockout mice …

Metabolic Reprogramming Driven By Ant2 Deficiency Augments T Cell Function And Anti-Tumor Immunity In Mice, Omri Yosef, Leonor Cohen-Daniel, Oded Shamriz, Zahala Bar-On, Wajeeh Salaymeh, Amijai Saragovi, Ifat Abramovich, Bella Agranovich, Veronika Lutz, Joseph Tam, Anna Permyakova, Eyal Gottlieb, Magdalena Huber, Michael Berger

Faculty, Staff and Student Publications

T cell activation requires a substantial increase in NAD+ production, often exceeding the capacity of oxidative phosphorylation (OXPHOS). To investigate how T cells adapt to this metabolic challenge, we generate T cell-specific ADP/ATP translocase-2 knockout (Ant2-/-) mice. Loss of Ant2, a crucial protein mediating ADP/ATP exchange between mitochondria and cytoplasm, induces OXPHOS restriction by limiting ATP synthase activity, thereby impeding NAD+ regeneration. Interestingly, Ant2-/- naïve T cells exhibit enhanced activation, proliferation and effector functions compared to wild-type controls. Metabolic profiling reveals that these T cells adopt an activated-like metabolic program with increased mitobiogenesis and anabolism. Lastly, pharmacological inhibition of ANT …