Biomedical Informatics Commons^™

Sugar Functionalized Collagen Material For Local Modulation Of Innate Immunity, Francesca Taraballi, Claudia Corbo, Julia Enterria-Rosales, John Otto Martinez, Silvia Minardi, Laura Pandolfi, Xing Wang, Ennio Tasciotti, Kavindra V Singh, Cesar A Arias, Bruna Corradetti

Faculty, Staff and Students Publications

Small alterations during the early stages of the innate immune response to an implant can drive large changes in adaptive immunity. Biomaterials for regenerative purposes can be engineered to modulate this immune response in beneficial ways. This study presents an innovative patch designed and functionalized to target the innate immunity at the implant site. Mannose moieties are incorporated into collagen patches, resulting in a technology called Local Immunotuning Patch (LIP), designed to directly interact with antigen presenting cells through their mannose receptor. In vitro, LIP shows anti-inflammatory effects on bone marrow-derived macrophages and inhibitory properties even on methicillin-resistant bacterial strains. …

Minimum Core Data Elements For Evaluation Of Thoracic Aortic Disease, Andreina Carbone, Mary J Roman, Melissa L Russo, Kathryn W Holmes, Maya Brown-Zimmerman, John Elefteriades, Catherine M Otto, Nicholas S Burris, Carlos Alberto Campello Jorge, Scott C Deroo, Maral Ouzounian, Matthew D Solomon, Jay D Humphrey, Bart Loeys, Shaine A Morris, Guillaume Jondeau, Scott A Lemaire, Sherene Shalhub, Siddharth K Prakash

Faculty, Staff and Students Publications

Thoracic aortic aneurysms predisposing to aortic dissections are rare but potentially deadly conditions that can be inherited in families. Understanding the natural history and genetic causes of thoracic aortic disease (TAD) requires international collaboration. The aim of this project is to provide core data elements that can be assessed directly and summarized efficiently in research records while developing standards to harmonize data across registries and clinical trials. Ten contemporary TAD registries were analyzed to identify significant gaps in the amount and types of data that are needed for accurate, verifiable, and reproducible studies. The set of data elements recommended by …

Constitutive Il-7 Signaling Promotes Car-Nk Cell Survival In The Solid Tumor Microenvironment But Impairs Tumor Control, Matthew Dysthe, Ishwar Navin, Dayenne Van Leeuwen, Josue Pineda, Corrine Baumgartner, Cliona M Rooney, Robin Parihar

Faculty, Staff and Students Publications

Background: Adoptive transfer of chimeric antigen receptor (CAR)-expressing natural killer (NK) cells has demonstrated success against hematological malignancies. Efficacy against solid tumors has been limited by poor NK cell survival and function in the suppressive tumor microenvironment (TME). To enhance efficacy against solid tumors, stimulatory cytokines have been incorporated into CAR-NK cell therapeutic approaches. However, current cytokine strategies have limitations, including systemic toxicities, exogenous dependencies, and unwanted TME bystander effects. Here, we aimed to overcome these limitations by modifying CAR-NK cells to express a constitutively active interleukin (IL)-7 receptor, termed C7R, capable of providing intrinsic CAR-NK cell activation that does …

Elimination Of Hiv Reservoirs Harboring Intact Proviruses, Min Li, Khanghy Truong, Suman Sharma, Baichao Sun, Min Chen, Jason T Kimata, Jin Wang

Faculty, Staff and Students Publications

Background: Human immunodeficiency virus (HIV) establishes persistent infection by integrating its proviral DNA into the host genome. While most integrated proviruses are defective, a small portion of proviruses are intact that represent a major obstacle to achieving an HIV cure. We have designed an approach for selective elimination of host cells harboring replication-competent HIV (SECH), through inhibition of autophagy and anti-apoptotic molecules during viral reactivation. However, the effects of SECH on the dynamics of intact and defective HIV provirus remain unclear.

Methods: We isolated DNA from HIV-infected samples after SECH treatments. We analyzed HIV-1 proviruses in these samples by intact …

Gene Expression In Tumor And Adjacent Normal Tissues In Lung Adenocarcinoma Subtypes, Olga Y Gorlova, Ivan P Gorlov, R Taylor Ripley, Chao Cheng, Yafang Li, Bo Peng, Yanhong Liu, Hee-Jin Jang, Sung Wook Kang, Claire Lee, Priyanka Ranchod, Bryan M Burt, Hyun-Sung Lee, Christopher I Amos

Faculty, Staff and Students Publications

Background: Lung adenocarcinoma (LUAD) has several histologically distinct subtypes that differ by a number of clinical features including patient survival. Molecular mechanisms underlying histological and clinical differences between subtypes remain poorly understood.

Methods: We conducted a comparative analyses of gene expression in acinar, lepidic, papillary and solid subtypes, as well as mucinous adenocarcinoma. We used a novel, more efficient approach to identify subtype-specific genes. We compared the mean gene expression level separately for tumors and adjacent normal tissue with pure or a highly represented (≥ 75%) subtype of interest to the mean expression in tumors where the subtype of interest …

The Co-Occurrence Of Autism Spectrum Disorder And Aarskog-Scott Syndrome In An Accomplished Young Man, Raisa S Romanova, Oksana I Talantseva, Katerina V Lind, Victoria A Manasevich, Julia E Kuznetsova, Elena L Grigorenko

Faculty, Staff and Students Publications

Objectives/Background: Aarskog-Scott syndrome (AAS), also known as faciogenital dysplasia, is a rare X-linked genetic disorder primarily characterized by its diverse physical manifestations. Previous evidence suggests a potential association between AAS and neurodevelopmental disorders, including autism spectrum disorder (ASD).

Methods: This case study presents a male adolescent with ASD and a novel genetic variant in FGD1 underlying AAS. We conducted comprehensive clinical, genetic, and behavioral assessments to characterize the neurodevelopmental presentation. Moreover, we examined the existing literature on AAS and comorbid neurodevelopmental disorders.

Results: The patient demonstrated features consistent with both AAS and ASD, presenting with characteristic physical features of AAS …

Genomic Rare Variant Mechanisms For Congenital Cardiac Laterality Defect: A Digenic Model Approach, Archana Rai, Jonathan Klonowski, Bo Yuan, Karen J Coveler, Zain Dardas, Iman Egab, Jiaoyang Xu, Philip J Lupo, A J Agopian, Dennis Kostka, Cecilia W Lo, S Stephen Yi, Bruce D Gelb, Christine E Seidman, Eric Boerwinkle, Jennifer E Posey, Richard A Gibbs, James R Lupski, Shaine A Morris, Zeynep Coban-Akdemir

Faculty, Staff and Students Publications

Laterality defects are defined by perturbations in the usual left-right asymmetry of organs. The genetic etiology that underlies congenital heart disease (CHD) is often unknown (less than 40%), so we used a digenic model approach for the identification of contributing variants in known laterality-defect-associated genes (n = 115) in the exome/genome sequencing (ES/GS) data from individuals with clinically diagnosed laterality defects. The unsolved ES/GS data were analyzed from three CHD cohorts: Baylor College of Medicine-Genomics Research to Elucidate the Genetics of Rare Diseases (BCM-GREGoR; n= 251 proband ES), Gabriella Miller Kids First Pediatric Research Program (Kids First; n = 158 …

Environmental Exposures Increase Health Risks In Childhood Cancer Survivors, Omar Shakeel, Nicole M Wood, Hannah M Thompson, Michael E Scheurer, Mark D Miller

Faculty, Staff and Students Publications

Childhood cancer survivors (CCSs) are at increased risk for chronic health issues due to late effects of cancer and its treatment. We address the impact of environmental exposures, such as air pollution, tobacco smoke, extreme weather events, and pesticides, on the health and survival of CCSs. These environmental hazards have been associated with worsening health outcomes and decreased survival among CCSs on a global scale. We also highlight that providers at a major pediatric cancer center in the United States have limited knowledge and practical skills about environmental risk factors and how to reduce exposures. Our survey results show that …

Integrative Analysis Reveals The Prognostic Effects Of Epigenetic Regulators In Bladder Cancer, Venugopalareddy Mekala, Yupei Lin, Xiang Wang, Naail Chowdhury, Jianrong Li, Chao Cheng

Faculty, Staff and Students Publications

Background: Epigenetic regulatory genes (epiRG) are pivotal in the epigenetic regulation of the human genome, primarily through DNA and histone modifications. These genes are frequently mutated in human cancers, particularly bladder cancer (BC). However, the functional impact of epiRG mutations on patient outcomes remains poorly understood.

Methods: In this study, we developed gene signatures for the most frequent genomic aberrations of epiRG using The Cancer Genome Atlas Bladder Carcinoma (TCGA-BLCA) dataset and validated these signatures with independent tumor expression profiles for prognostic relevance. Furthermore, we evaluated the role of these signature scores in the immune system within the tumor microenvironment …

Glioblastoma-Instructed Astrocytes Suppress Tumour-Specific T Cell Immunity, Camilo Faust Akl, Brian M Andersen, Zhaorong Li, Federico Giovannoni, Martin Diebold, Liliana M Sanmarco, Michael Kilian, Luca Fehrenbacher, Florian Pernin, Joseph M Rone, Hong-Gyun Lee, Gavin Piester, Jessica E Kenison, Joon-Hyuk Lee, Tomer Illouz, Carolina M Polonio, Léna Srun, Jazmin Martinez, Elizabeth N Chung, Anton Schüle, Agustin Plasencia, Lucinda Li, Kylynne Ferrara, Mercedes Lewandrowski, Craig A Strathdee, Lorena Lerner, Christophe Quéva, Iain C Clark, Benjamin Deneen, Judy Lieberman, David H Sherr, Jack P Antel, Michael A Wheeler, Keith L Ligon, E Antonio Chiocca, Marco Prinz, David A Reardon, Francisco J Quintana

Faculty, Staff and Students Publications

Glioblastoma is the most common and aggressive primary brain cancer and shows minimal response to therapies. The immunosuppressive tumour microenvironment in glioblastoma contributes to the limited therapeutic response. Astrocytes are abundant in the central nervous system and have important immunoregulatory roles. However, little is known about their role in the immune response to glioblastoma1. Here we used single-cell and bulk RNA sequencing of clinical glioblastoma samples and samples from preclinical models, multiplexed immunofluorescence, in vivo CRISPR-based cell-specific genetic perturbations and in vitro mouse and human experimental systems to address this gap in knowledge. We identified an astrocyte subset …

Mechanisms Of Experience-Dependent Place-Cell Referencing In Hippocampal Area Ca1, Fish Kunxun Qian, Yiding Li, Jeffrey C Magee

Faculty, Staff and Students Publications

Hippocampal CA1 place cells (PCs) encode both space- and goal-referenced information to support a cognitive map. The mechanism of this referencing and the role of experience remain poorly understood. Here we longitudinally recorded PC activity while head-fixed mice performed a spatial learning task on a treadmill. In a familiar environment, the CA1 representation consisted of PCs that were referenced to either specific spatial locations or a reward goal in approximately equal proportions; however, the CA1 representation became predominately goal-referenced upon exposure to a novel environment, as space-referenced PCs adaptively switched reference frames. Intracellular membrane potential recordings revealed that individual CA1 …

Crispr-Cas9 Mediated Proteinase 3 Autoantigen Deletion As A Treatment Strategy For Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis, Uwe Jerke, Claudia Eulenberg-Gustavus, Dimitrios Laurin Wagner, Adrian Schreiber, Ralph Kettritz

Faculty, Staff and Students Publications

Introduction: Proteinase 3 (PR3) is a major autoantigen in patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). Here, we performed a proof-of-principle study using ex vivo CRISPR-Cas9 guided gene editing to eliminate the PR3 autoantigen as an alternative to suppressing the autoimmune response to PR3.

Methods: A ribonucleoprotein (RNP) complex of Cas9 protein and a PR3-specific single guide-RNA was transfected into human CD34+ hematopoietic stem and progenitor cells (HSPC) by electroporation. Effects on PR3 protein abundance, neutrophil differentiation, and ANCA-dependent and -independent neutrophil responses were assessed.

Results: Gene editing introduced a frame shift in exon 2 of PRTN3. Consequently, PR3 …

Pediatric Cancer Predisposition And Surveillance Update: Summary Perspective And Future Directions, Garrett M Brodeur, Lisa R Diller, Kim E Nichols, Sharon E Plon, Christopher C Porter, David Malkin

Faculty, Staff and Students Publications

An increasing number of studies suggest that a significant proportion of children with cancer harbor an underlying predisposition to malignancy, and it is likely that this proportion will only increase. Targeted surveillance for these individuals would likely improve outcomes. Historically, however, for most predisposition syndromes, there were no standardized surveillance protocols for early detection of cancer in predisposed individuals. Therefore, the Pediatric Cancer Working Group of the American Association for Cancer Research convened a workshop in 2016 to develop consensus surveillance recommendations (published in 2017) for children and adolescents with the most common cancer predisposition syndromes. These recommendations provided a …

Functional Assays In Drosophila Facilitate Classification Of Variants Of Uncertain Significance Associated With Rare Diseases, Jung-Wan Mok, Shelley B Gibson, Haley A Dostalik, Shinya Yamamoto

Faculty, Staff and Students Publications

Individuals living with rare diseases often undergo a frustrating and expensive diagnostic odyssey. Clinical geneticists who analyze exome or genome sequencing data from rare disease patients often encounter a list of variants of uncertain significance (VUS) in known disease-causing genes or rare variants in genes of uncertain significance (GUS) that are difficult to interpret, even with the integration of the latest bioinformatic tools. In this Perspective, we review how studies using the fruit fly Drosophila melanogaster have facilitated rare disease diagnosis by uncovering the clinical relevance of GUS and classifying rare variants into specific allelic categories (loss-of-function or gain-of-function, Muller's …

Endothelium- And Fibroblast-Derived C-Type Natriuretic Peptide Prevents The Development And Progression Of Aortic Aneurysm, Aisah A Aubdool, Amie J Moyes, Cristina Perez-Ternero, Reshma S Baliga, Jaspinder Singh Sanghera, M Taaha Syed, Kareemah Jaigirdar, Anmolpreet K Panesar, Janice C Tsui, Yanming Li, Hernan G Vasquez, Ying H Shen, Scott A Lemaire, Juliette Raffort, Ziad Mallat, Hong S Lu, Alan Daugherty, Adrian J Hobbs

Faculty, Staff and Students Publications

Background: Thoracic (TAA) and abdominal (AAA) aortic aneurysm are life-threatening diseases characterized by dilation, inflammation, and structural weakness; development of pharmacological therapies is desperately needed. CNP (C-type natriuretic peptide) plays a key role in vascular homeostasis, mediating vasodilator, anti-inflammatory, and antiatherogenic actions. Since such processes drive AA, we determined the role of endogenous CNP in offsetting pathogenesis.

Methods: Tissue from patients with AA was analyzed to determine the consequences on CNP signaling. Ascending and suprarenal aortic diameters were assessed at baseline and following Ang II (angiotensin II; 1.44 mg/kg per day) infusion in wild-type, endothelium-restricted (ecCNP-/-), fibroblast-restricted (fbCNP-/-), global CNP …

Differences In Arterial Events In Vascular Ehlers-Danlos, Loeys-Dietz, And Marfan Syndrome, Ernesto Calderon-Martinez, Walter V Velasco, Dongchuan Guo, Ellen H Hostetler, Zhang Xun, Sara Stephens, Sherene Shalhub, Julie De Backer, Maral Ouzounian, Scott A Lemaire, Olivier Milleron, Nadine Hanna, Pauline Arnaud, Maria Tchitchinadze, Siddharth K Prakash, Mark Lindsay, Julien Marcadier, Richmond Jeremy, Shaine A Morris, Anji T Yetman, Catherine Boileau, Alan C Braverman, Guillaume Jondeau, Dianna M Milewicz

Faculty, Staff and Students Publications

Background: Heritable thoracic aortic disease is due to altered genes that confer a highly penetrant risk for thoracic aortic aneurysm and dissection, and a subset of these genes also cause aneurysms and dissections of peripheral arteries beyond the aorta. Arterial aneurysms, dissections, and ruptures are associated with pathogenic variants (PVs) in COL3A1, which is responsible for vascular Ehlers-Danlos syndrome, but arterial events are rare in Marfan syndrome due to PVs in FBN1, and poorly characterized in Loeys-Dietz syndrome due to PVs in the transforming growth factor (TGF)-β pathway genes.

Objectives: This study sought to define the relative risk of arterial …

Primary Mouse Choroidal Endothelial Cell Culture, Qiuhua Yang, Yongfeng Cai, Qian Ma, Yuqing Huo

Faculty, Staff and Students Publications

The study of choroidal endothelial cells is essential for understanding the pathological mechanisms underlying choroidal neovascularization and other vision-threatening disorders. Traditional methods for isolating and culturing primary endothelial cells often yield mixed populations or require specialized equipment, limiting their widespread use. Here, we present a straightforward protocol for isolating and culturing primary mouse choroidal endothelial cells. This protocol involves enzymatic digestion of choroidal tissue, magnetic-activated cell sorting (MACS) to enrich CD31+ endothelial cells, and optimized culture conditions to promote cell proliferation and maintain endothelial phenotype. The protocol is strategic, reproducible, and requires minimal specialized equipment, making it accessible for researchers …

Oncolytic Adeno-Immunotherapy Improves Allogeneic Adoptive Her2car-Nk Function Against Pancreatic Ductal Adenocarcinoma, Greyson Biegert, Amanda Rosewell Shaw, Daisuke Morita, Caroline Porter, Ryu Matsumoto, Lisa Jatta, Noah Crooks, Mae Woods, Qizhi Cathy Yao, Robin Parihar, Masataka Suzuki

Faculty, Staff and Students Publications

Pancreatic ductal adenocarcinoma (PDAC) responds poorly to conventional treatments and immunotherapy. We previously developed a binary oncolytic/helper-dependent adenovirus system (CAdTrio) that facilitated oncolysis and expressed the immunomodulatory molecule interleukin-12 and a programmed death ligand 1 (PD-L1) blocking mini-antibody. Given that CAdTrio enhanced endogenous natural killer (NK) cell anti-tumor activity in humanized mice bearing PDAC tumors and that NK cells can be adoptively transferred to patients safely in the allogeneic setting, we hypothesized that a combination of CAdTrio and allogeneic NK cells expressing a HER2-specific chimeric antigen receptor (HER2.CAR-NK) would be an effective, entirely “off-the-shelf” treatment against …

Graphage: Unleashing The Power Of Graph Neural Network To Decode Epigenetic Aging, Saleh Sakib Ahmed, Nahian Shabab, Abul Hassan Samee, M Sohel Rahman

Faculty, Staff and Students Publications

DNA methylation is a crucial epigenetic marker used in various clocks to predict epigenetic age. However, many existing clocks fail to account for crucial information about CpG sites and their interrelationships, such as co-methylation patterns. We present a novel approach to represent methylation data as a graph, using methylation values and relevant information about CpG sites as nodes, and relationships like co-methylation, same gene, and same chromosome as edges. We then use a graph neural network (GNN) to predict age. Thus our model, GraphAge leverages both the structural and positional information for prediction as well as better interpretation. Although, we …

Ccaat/Enhancer-Binding Proteins Α And Β Regulate Ovulation And Gene Expression Via Dose- And Stage-Dependent Mechanisms, Hanxue Zhang, Rainer B Lanz, Jimmy Dhillon, Paul D Soloway, Bo Shui, Yi Athena Ren

Faculty, Staff and Students Publications

The preovulatory luteinizing hormone (LH) surge orchestrates complex cellular and molecular events leading to ovulation. CCAAT/enhancer-binding proteins α and β (C/EBPα/β) are transcription factors acutely induced by the LH surge and crucial for ovulation and granulosa cell luteinization. However, biological processes (BPs) and their regulatory mechanisms downstream of C/EBPα/β in the preovulatory ovary are not completely understood. To address this knowledge gap, we generated Cebpa/bfl/fl;Pgr-Cre mutants and compared them with Cebpa/bfl/fl;Cyp19a1-Cre mutant female mice: Cebpa/bfl/fl;Cyp19a1-Cre mutants have undetectable levels of C/EBPα/β throughout the preovulatory stages and do not ovulate, aligning with previous reports; and Cebpa/bfl/fl;Pgr-Cre mutants present gradual depletion of …

Approach To The Patient: From Endocrinopathy To The Diagnosis Of A Histiocytic Disorder, Polyzois Makras, Dana Erickson, Caroline J Davidge-Pitts, Eli L Diamond, Carl E Allen, Kenneth L Mcclain, Jithma P Abeykoon, Ronald S Go, Krishmita Siwakoti, Houman Sotoudeh, Aishwarya Ravindran, Lucinda M Gruber, Gaurav Goyal

Faculty, Staff and Students Publications

Endocrinopathies are frequently the initial presentation of histiocytic neoplasms, which are rare hematologic disorders affecting multiple organ systems. Langerhans cell histiocytosis and Erdheim-Chester disease are 2 such disorders known to infiltrate the hypothalamus and/or pituitary gland, leading to arginine vasopressin deficiency (AVP-D) and anterior pituitary dysfunction (APD) in 20% to 30% of cases, often as the first manifestation. Conversely, histiocytic disorders account for a notable proportion (10-15%) of all pituitary stalk lesions. The diagnosis of histiocytoses is often delayed in such cases due to the nonspecific presentation of endocrinopathies and pituitary involvement. Consequently, endocrinologists are at the frontline and uniquely …

The Genestar Manual For Biospecimen Collection Biobanking And Omics Data Generation From Commercial Space Missions, Aparna Krishnavajhala, Marie-Claude Gingras, Emmanuel Urquieta, Hsu Chao, Dilrukshi Bandaranaike, Yi Chen, Sravya Bhamidipati, Viktoriya Korchina, S Michelle Griffin, Michal M Masternak, Hannah Moreno, Javid Mohammed, Mullai Murugan, Jennifer E Posey, Jimmy H Wu, Donna Muzny, Richard A Gibbs, Harsha Doddapaneni

Faculty, Staff and Students Publications

The surge in commercial and civilian spaceflight enables the systematic and longitudinal, large-scale biospecimen collection to understand the prospective effects of space travel on human health. The Genomics and Space Medicine (Space Omics) project at BCM-HGSC involves a comprehensive biospecimen collection plan from commercial/private space flight participants. The manuscript addresses the critical gaps in the biospecimen collection process including details of the informed consent process, a provision for subjects to obtain custom CLIA-WGS reports, a data dictionary and a LIMS enabled biobank. The manuscript also discusses the biospecimens collection, processing methodologies and nucleic acid suitability for Omics data generation. Results …

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 …

Tau Depletion Diminishes Vascular Amyloid-Related Deficits In A Mouse Model Of Cerebral Amyloid Angiopathy, Nur Jury-Garfe, Enrique Chimal-Juárez, Henika Patel, Jonathan Martinez-Pinto, Kathryn Vanderbosch, Muriel D Mardones, Abigail Perkins, Gonzalo Viana Di Prisco, Yamil Marambio, Ruben Vidal, Brady K Atwood, Cristian A Lasagna-Reeves

Faculty, Staff and Students Publications

Introduction: Tau is essential for amyloid beta (Aβ)-induced synaptic and cognitive deficits in Alzheimer's disease (AD), making its downregulation a therapeutic target. Cerebral amyloid angiopathy (CAA), a major vascular contributor to cognitive decline, affects over 90% of patients with AD. This study explores the impact of tau downregulation on CAA pathogenesis.

Methods: We crossed the Familial Danish Dementia mouse model (Tg-FDD), which develops vascular amyloid, with tau-null (mTau-/-) mice to generate a CAA model lacking endogenous tau (Tg-FDD/mTau-/-). Behavioral, electrophysiological, histological, and transcriptomic analyses were performed.

Results: Tau depletion ameliorated motor and synaptic impairments, reduced vascular amyloid deposition, and prevented …

The Influence Of The American Association For Thoracic Surgery On Clinical Trial Development By Cardiothoracic Surgeons, Adishesh K Narahari, Taylor M Horgan, Anirudha S Chandrabhatla, Abhinav Kareddy, Ajami Gikandi, Marco A Zenati, David Harpole, David Jones, Leora T Yarboro, Bryan Burt, A Sasha Krupnick, J Hunter Mehaffey

Faculty, Staff and Students Publications

Objective: Clinical trials play a critical role in the rapidly evolving field of cardiothoracic surgery and the American Association for Thoracic Surgery Clinical Trials Methods Course has provided a biannual symposium led by preeminent surgeons with vast experience in planning, conducting, and analyzing surgical clinical trials. This study hypothesizes that participation in the course is associated with future success in clinical trial leadership.

Methods: A list of course attendees (2014-2022) was queried in ClinicalTrials.gov, a database of clinical trials funded by the US Department of Health and Human Services and the National Institutes of Health. The type of clinical trial …

Emapalumab Treatment In Rheumatologic Disease-Associated Hemophagocytic Lymphohistiocytosis: A Plain Language Summary, Shanmuganathan Chandrakasan, Carl E Allen, Deepika Bhatla, John Carter, May Chien, Robert Cooper, Lauren Draper, Olive S Eckstein, Rabi Hanna, J Allyson Hays, Michelle L Hermiston, Ashley P Hinson, Patricia M Hobday, Michael S Isakoff, Michael B Jordan, Jennifer W Leiding, Renee Modica, Taizo A Nakano, Abiola Oladapo, Sachit A Patel, Priti Pednekar, Mona Riskalla, Susmita N Sarangi, Prakash Satwani, Anand Tandra, Kelly J Walkovich, John D Yee, Adi Zoref-Lorenz, Edward M Behrens

Faculty, Staff and Students Publications

What is this summary about? Hemophagocytic lymphohistiocytosis (HLH) is a rare disease caused by overactivation of the body’s natural defense mechanism (the immune system) against infection. In untreated HLH, uncontrolled inflammation (hyperinflammation) can cause significant damage to the body’s organs and death. HLH can occur due to genetic defects (primary HLH) or as a complication or worsening of an underlying disease such as rheumatologic disease, cancer, or infection (secondary HLH).Interferon-gamma (IFNγ) is a type of protein that is overproduced in HLH and causes hyperinflammation. Emapalumab is a medicine that blocks IFNγ activity. The REAL-HLH study described the use of emapalumab …

Nanoparticle Contrast-Enhanced Computed Tomography And Magnetic Resonance Imaging Of Vascularization Of A Subcutaneous Niche For Islet Transplantation, Simone Capuani, Jocelyn Nikita Campa-Carranza, Nathanael Hernandez, Renuka T R Menon, Rohan Bhavane, Gabrielle E Rome, Laxman Devkota, Ketan B Ghaghada, Ananth V Annapragada, Corrine Ying Xuan Chua, Andrew A Badachhape, Alessandro Grattoni

Faculty, Staff and Students Publications

Revascularization plays a critical role in the successful engraftment of transplanted pancreatic islets, which are inherently rich in capillaries to meet their high metabolic demands. Innovative islet encapsulation strategies such as the NICHE (neovascularized implantable cell homing and encapsulation), generate a prevascularized transplantation site that allows for direct integration of the graft with the systemic circulation. Timing the transplantation is key to maximizing islet engraftment and survival, especially in diabetic individuals, who exhibit impaired wound healing. Therefore, in this study, we explored different methods to assess vascular development within NICHE in vivo in a non-invasive fashion. We effectively tracked neoangiogenesis …

Cross-Tissue Coordination Between Slc Nucleoside Transporters Regulates Reproduction In Caenorhabditis Elegans, Youchen Guan, Yong Yu, Shihong M Gao, Lang Ding, Qian Zhao, Meng C Wang

Faculty, Staff and Students Publications

Metabolism is fundamental to organism physiology and pathology. From the intricate network of metabolic reactions, diverse chemical molecules, collectively termed metabolites, are produced. In multicellular organisms, metabolite communication between different tissues is vital for maintaining homeostasis and adaptation. However, the molecular mechanisms mediating these metabolite communications remain poorly understood. Here, we focus on nucleosides and nucleotides, essential metabolites involved in multiple cellular processes, and report the pivotal role of the SLC29A family of transporters in mediating nucleoside coordination between the soma and the germline. Through genetic analysis, we discovered that two Caenorhabditis elegans homologs of SLC29A transporters, Equilibrative Nucleoside Transporter …

Temi: Tissue-Expansion Mass-Spectrometry Imaging, Hua Zhang, Lang Ding, Amy Hu, Xudong Shi, Penghsuan Huang, Haiyan Lu, Paul W Tillberg, Meng C Wang, Lingjun Li

Faculty, Staff and Students Publications

The spatial distribution of diverse biomolecules in multicellular organisms is essential for their physiological functions. High-throughput in situ mapping of biomolecules is crucial for both basic and medical research, and requires high scanning speed, spatial resolution, and chemical sensitivity. Here we developed a tissue-expansion method compatible with matrix-assisted laser desorption/ionization mass-spectrometry imaging (TEMI). TEMI reaches single-cell spatial resolution without sacrificing voxel throughput and enables the profiling of hundreds of biomolecules, including lipids, metabolites, peptides (proteins), and N-glycans. Using TEMI, we mapped the spatial distribution of biomolecules across various mammalian tissues and uncovered metabolic heterogeneity in tumors. TEMI can be easily …

Region-Specific Roles Of Oviductal Motile Cilia In Oocyte/Embryo Transport And Fertility†, Deirdre M Scully, Tian Xia, Guzel R Musina, Michaela A Mccown, Kohei Umezu, Bonnie K Kircher, Richard R Behringer, Irina V Larina

Faculty, Staff and Students Publications

The physiological and clinical importance of motile cilia in reproduction is well recognized; however, the specific role they play in transport through the oviduct and how ciliopathies lead to subfertility and infertility are still unclear. The contribution of cilia beating, fluid flow, and smooth muscle contraction to overall progressive transport within the oviduct remains under debate. Therefore, we investigated the role of cilia in the oviduct transport of preimplantation eggs/embryos using a combination of genetic and advanced imaging approaches. We show that the region of the oviduct where cumulus-oocyte complex circling occurs, around the time of fertilization, is correlated with …