Digital Commons Network^™

The Covert Symphony: Cellular And Molecular Accomplices In Breast Cancer Metastasis, Hongjiang Si, Madelyn Esquivel, Erika Mendoza Mendoza, Kevin Roarty

Faculty, Staff and Students Publications

Breast cancer has emerged as the most commonly diagnosed cancer and primary cause of cancer-related deaths among women worldwide. Although significant progress has been made in targeting the primary tumor, the effectiveness of systemic treatments to prevent metastasis remains limited. Metastatic disease continues to be the predominant factor leading to fatality in the majority of breast cancer patients. The existence of a prolonged latency period between initial treatment and eventual recurrence in certain patients indicates that tumors can both adapt to and interact with the systemic environment of the host, facilitating and sustaining the progression of the disease. In order …

Size Distributions Of Intracellular Condensates Reflect Competition Between Coalescence And Nucleation, Daniel S W Lee, Chang-Hyun Choi, David W Sanders, Lien Beckers, Joshua A Riback, Clifford P Brangwynne, Ned S Wingreen

Faculty, Staff and Students Publications

Phase separation of biomolecules into condensates has emerged as a mechanism for intracellular organization and affects many intracellular processes, including reaction pathways through the clustering of enzymes and pathway intermediates. Precise and rapid spatiotemporal control of reactions by condensates requires tuning of their sizes. However, the physical processes that govern the distribution of condensate sizes remain unclear. Here we show that both native and synthetic condensates display an exponential size distribution, which is captured by Monte Carlo simulations of fast nucleation followed by coalescence. In contrast, pathological aggregates exhibit a power-law size distribution. These distinct behaviours reflect the relative importance …

The Fgfr1 Signaling Pathway Upregulates The Oncogenic Transcription Factor Foxq1 To Promote Breast Cancer Cell Growth, Yan Lin, Fengkang Lin, Zhuoran Zhang, Lijia Peng, Wenli Yang, Mao Yang, Bo Luo, Ting Wu, Dabing Li, Xuesen Li, Bing Ran, Songyot Anuchapreeda, Rujirek Chaiwongsa, Pinyaphat Khamphikham, Suwit Duangmano, Jianming Xu, Tao He, Sakorn Pornprasert

Faculty, Staff and Students Publications

FGFR1 is a receptor tyrosine kinase deregulated in certain breast cancers (BCs) with a poor prognosis. Although FGFR1-activated phosphorylation cascades have been mapped, the key genes regulated by FGFR1 in BC are largely unclear. FOXQ1 is an oncogenic transcription factor. Although we found that activation of FGFR1 robustly upregulated FOXQ1 mRNA, how FGFR1 regulates FOXQ1 gene expression and whether FOXQ1 is essential for FGFR1-stimulated cell proliferation are unknown. Herein, we confirmed that activation of FGFR1 robustly upregulated FOXQ1 mRNA and protein in BC cells. Knockdown of FOXQ1 blocked the FGFR1 signaling-stimulated BC cell proliferation, colony formation, and xenograft tumor growth. …

Proceedings Of The 2023 Santa Fe Bone Symposium: Progress And Controversies In The Management Of Patients With Skeletal Diseases, E Michael Lewiecki, Teresita Bellido, John P Bilezikian, Jacques P Brown, Azeez Farooki, Christopher S Kovacs, Brendan Lee, William D Leslie, Michael R Mcclung, Mark L Prasarn, Deborah E Sellmeyer

Faculty, Staff and Students Publications

The Santa Fe Bone Symposium (SFBS) held its 23rd annual event on August 5-6, 2023, in Santa Fe, New Mexico, USA. Attendees participated in-person and remotely, representing many states and countries. The program included plenary presentations, panel discussions, satellite symposia, a Project ECHO workshop, and a session on healthcare policy and reimbursement for fracture liaison programs. A broad range of topics were addressed, including transitions of osteoporosis treatments over a lifetime; controversies in vitamin D; update on Official Positions of the International Society for Clinical Densitometry; spine surgery and bone health; clinical applications of bone turnover markers; basic bone biology …

Circulating Tumor Dna Sequencing Of Pediatric Solid And Brain Tumor Patients: An Institutional Feasibility Study, Ross Mangum, Jacquelyn Reuther, Koel Sen Baksi, Ilavarasi Gandhi, Ryan C Zabriskie, Alva Recinos, Robin Raesz-Martinez, Frank Y Lin, Samara L Potter, Andrew C Sher, Stephen F Kralik, Carrie A Mohila, Murali M Chintagumpala, Donna Muzny, Jianhong Hu, Richard A Gibbs, Kevin E Fisher, Juan Carlos Bernini, Jonathan Gill, Timothy C Griffin, Gail E Tomlinson, Kelly L Vallance, Sharon E Plon, Angshumoy Roy, D Williams Parsons

Faculty, Staff and Students Publications

The potential of circulating tumor DNA (ctDNA) analysis to serve as a real-time "liquid biopsy" for children with central nervous system (CNS) and non-CNS solid tumors remains to be fully elucidated. We conducted a study to investigate the feasibility and potential clinical utility of ctDNA sequencing in pediatric patients enrolled on an institutional clinical genomics trial. A total of 240 patients had tumor DNA profiling performed during the study period. Plasma samples were collected at study enrollment from 217 patients and then longitudinally from a subset of patients. Successful cell-free DNA extraction and quantification occurred in 216 of 217 (99.5%) …

Differential Regulation Of Skeletal Stem/Progenitor Cells In Distinct Skeletal Compartments, Jea Giezl Niedo Solidum, Youngjae Jeong, Francisco Heralde, Dongsu Park

Faculty, Staff and Students Publications

Skeletal stem/progenitor cells (SSPCs), characterized by self-renewal and multipotency, are essential for skeletal development, bone remodeling, and bone repair. These cells have traditionally been known to reside within the bone marrow, but recent studies have identified the presence of distinct SSPC populations in other skeletal compartments such as the growth plate, periosteum, and calvarial sutures. Differences in the cellular and matrix environment of distinct SSPC populations are believed to regulate their stemness and to direct their roles at different stages of development, homeostasis, and regeneration; differences in embryonic origin and adjacent tissue structures also affect SSPC regulation. As these SSPC …

Variantsurvival: A Tool To Identify Genotype-Treatment Response, Thomas Krannich, Marina Herrera Sarrias, Hiba Ben Aribi, Moustafa Shokrof, Alfredo Iacoangeli, Ammar Al-Chalabi, Fritz J Sedlazeck, Ben Busby, Ahmad Al Khleifat

Faculty, Staff and Students Publications

Associated Data

A Population-Based Assessment Of Metastatic Hepatoblastoma In Texas Reveals Ethnic Disparities, Andres F Espinoza, Michael E Scheurer, Tiffany M Chambers, Sanjeev A Vasudevan, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: Hepatoblastoma (HB) is the most common primary liver cancer in children with emerging evidence that incidence is increasing globally. While overall survival for low risk hepatoblastoma is >90%, children with metastatic disease have worse survival. As identifying factors associated with high-risk disease is critical for improving outcomes for these children, a need for a further understanding of the epidemiology of hepatoblastoma is warranted. Therefore, we conducted a population-based epidemiologic study of hepatoblastoma in Texas, a large state characterized by ethnic and geographic diversity.

METHODS: Information on children diagnosed with hepatoblastoma at 0-19 years of age for the period of …

Ultrahigh Resolution Lipid Mass Spectrometry Imaging Of High-Grade Serous Ovarian Cancer Mouse Models, Xin Ma, Andro Botros, Sylvia R Yun, Eun Young Park, Olga Kim, Soojin Park, Thu-Huyen Pham, Ruihong Chen, Murugesan Palaniappan, Martin M Matzuk, Jaeyeon Kim, Facundo M Fernández

Faculty, Staff and Students Publications

No effective screening tools for ovarian cancer (OC) exist, making it one of the deadliest cancers among women. Considering that little is known about the detailed progression and metastasis mechanism of OC at a molecular level, it is crucial to gain more insights into how metabolic and signaling alterations accompany its development. Herein, we present a comprehensive study using ultra-high-resolution Fourier transform ion cyclotron resonance matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to investigate the spatial distribution and alterations of lipids in ovarian tissues collected from double knockout (n = 4) and triple mutant mouse models (n …

Disease Modeling Of Adamts9-Related Nephropathy Using Kidney Organoids Reveals Its Roles In Tubular Cells And Podocytes, Seyoung Yu, Yo Jun Choi, John Hoon Rim, Hye-Youn Kim, Nasim Bekheirnia, Sarah Jane Swartz, Hongzheng Dai, Shen Linda Gu, Soyeon Lee, Ryuichi Nishinakamura, Friedhelm Hildebrandt, Mir Reza Bekheirnia, Heon Yung Gee

Faculty, Staff and Students Publications

INTRODUCTION: Mutations in ADAMTS9 cause nephronophthisis-related ciliopathies (NPHP-RC), which are characterized by multiple developmental defects and kidney diseases. Patients with NPHP-RC usually have normal glomeruli and negligible or no proteinuria. Herein, we identified novel compound-heterozygous ADAMTS9 variants in two siblings with NPHP-RC who had glomerular manifestations, including proteinuria.

METHODS: To investigate whether ADAMTS9 dysfunction causes NPHP and glomerulopathy, we differentiated ADAMTS9 knockout human induced pluripotent stem cells (hiPSCs) into kidney organoids. Single-cell RNA sequencing was utilized to elucidate the gene expression profiles from the ADAMTS9 knockout kidney organoids.

RESULTS:ADAMTS9 knockout had no effect on nephron differentiation; however, it reduced …

Establishing An Online Resource To Facilitate Global Collaboration And Inclusion Of Underrepresented Populations: Experience From The Mjff Global Genetic Parkinson’S Disease Project, Eva-Juliane Vollstedt, Harutyun Madoev, Anna Aasly, Azlina Ahmad-Annuar, Bashayer Al-Mubarak, Roy N Alcalay, Victoria Alvarez, Ignacio Amorin, Grazia Annesi, David Arkadir, Soraya Bardien, Roger A Barker, Melinda Barkhuizen, A Nazli Basak, Vincenzo Bonifati, Agnita Boon, Laura Brighina, Kathrin Brockmann, Andrea Carmine Belin, Jonathan Carr, Jordi Clarimon, Mario Cornejo-Olivas, Leonor Correia Guedes, Jean-Christophe Corvol, David Crosiers, Joana Damásio, Parimal Das, Patricia De Carvalho Aguiar, Anna De Rosa, Jolanta Dorszewska, Sibel Ertan, Rosangela Ferese, Joaquim Ferreira, Emilia Gatto, Gençer Genç, Nir Giladi, Pilar Gómez-Garre, Hasmet Hanagasi, Nobutaka Hattori, Faycal Hentati, Dorota Hoffman-Zacharska, Sergey N Illarioshkin, Joseph Jankovic, Silvia Jesús, Valtteri Kaasinen, Anneke Kievit, Peter Klivenyi, Vladimir Kostic, Dariusz Koziorowski, Andrea A Kühn, Anthony E Lang, Shen-Yang Lim, Chin-Hsien Lin, Katja Lohmann, Vladana Markovic, Mika Henrik Martikainen, George Mellick, Marcelo Merello, Lukasz Milanowski, Pablo Mir, Özgür Öztop-Çakmak, Márcia Mattos Gonçalves Pimentel, Teeratorn Pulkes, Andreas Puschmann, Ekaterina Rogaeva, Esther M Sammler, Maria Skaalum Petersen, Matej Skorvanek, Mariana Spitz, Oksana Suchowersky, Ai Huey Tan, Pichet Termsarasab, Avner Thaler, Vitor Tumas, Enza Maria Valente, Bart Van De Warrenburg, Caroline H Williams-Gray, Ruey-Mei Wu, Baorong Zhang, Alexander Zimprich, Justin Solle, Shalini Padmanabhan, Christine Klein

Faculty, Staff and Students Publications

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, …

The Role Of Hyperexcitability In Gliomagenesis, Eric A Goethe, Benjamin Deneen, Jeffrey Noebels, Ganesh Rao

Faculty, Staff and Students Publications

Glioblastoma is the most common malignant primary brain tumor. Recent studies have demonstrated that excitatory or activity-dependent signaling-both synaptic and non-synaptic-contribute to the progression of glioblastoma. Glutamatergic receptors may be stimulated via neuron-tumor synapses or release of glutamate by the tumor itself. Ion currents generated by these receptors directly alter the structure of membrane adhesion molecules and cytoskeletal proteins to promote migratory behavior. Additionally, the hyperexcitable milieu surrounding glioma increases the rate at which tumor cells proliferate and drive recurrent disease. Inhibition of excitatory signaling has shown to effectively reduce its pro-migratory and -proliferative effects.

From Concept To Delivery: A Yeast-Expressed Recombinant Protein-Based Covid-19 Vaccine Technology Suitable For Global Access, Peter J Hotez, Rakesh Adhikari, Wen-Hsiang Chen, Yi-Lin Chen, Portia Gillespie, Nelufa Y Islam, Brian Keegan, Rakhi Tyagi Kundu, Jungsoon Lee, Zhuyun Liu, Jason T Kimata, Numan Oezguen, Jeroen Pollet, Cristina Poveda, Kay Razavi, Shannon E Ronca, Ulrich Strych, Syamala R Thimmiraju, Leroy Versteeg, Maria Jose Villar-Mondragon, Junfei Wei, Bin Zhan, Maria Elena Bottazzi

Faculty, Staff and Students Publications

Introduction: The development of a yeast-expressed recombinant protein-based vaccine technology co-developed with LMIC vaccine producers and suitable as a COVID-19 vaccine for global access is described. The proof-of-concept for developing a SARS-CoV-2 spike protein receptor-binding domain (RBD) antigen as a yeast-derived recombinant protein vaccine technology is described.

Areas covered: Genetic Engineering: The strategy is presented for the design and genetic modification used during cloning and expression in the yeast system. Process and Assay Development: A summary is presented of how a scalable, reproducible, and robust production process for the recombinant protein COVID-19 vaccine antigen was developed. Formulation and Pre-clinical Strategy: …

Cumulative Comorbid Conditions Influence Mortality Risk After Staged Palliation For Hypoplastic Left Heart Syndrome And Variants, Emily R Backes, Natasha S Afonso, Danielle Guffey, James S Tweddell, Sarah Tabbutt, Nancy A Rudd, Ginny O'Harrow, Silvana Molossi, George M Hoffman, Garick Hill, Jeffrey S Heinle, Priya Bhat, Jeffrey B Anderson, Nancy S Ghanayem

Faculty, Staff and Students Publications

Objective: Prematurity, low birth weight, genetic syndromes, extracardiac conditions, and secondary cardiac lesions are considered high-risk conditions associated with mortality after stage 1 palliation. We report the impact of these conditions on outcomes from a prospective multicenter improvement collaborative.

Methods: The National Pediatric Cardiology Quality Improvement Collaborative Phase II registry was queried. Comorbid conditions were categorized and quantified to determine the cumulative burden of high-risk diagnoses on survival to the first birthday. Logistic regression was applied to evaluate factors associated with mortality.

Results: Of the 1421 participants, 40% (575) had at least 1 high-risk condition. The aggregate high-risk group had …

Editorial: The Regulatory Immune System As A Target To Improve Adjuvants And Novel Vaccines, Carlos Jiménez-Cortegana, Cristina Poveda, Gabriel Cabrera

Faculty, Staff and Students Publications

No abstract provided.

Melatonin Attenuates Mitochondrial Damage In Aristolochic Acid-Induced Acute Kidney Injury, Jian Sun, Jinjin Pan, Qinlong Liu, Jizhong Cheng, Qing Tang, Yuke Ji, Ke Cheng, Rui Wang, Liang Liu, Dingyou Wang, Na Wu, Xu Zheng, Junxia Li, Xueyan Zhang, Zhilong Zhu, Yanchun Ding, Feng Zheng, Jia Li, Ying Zhang, Yuhui Yuan

Faculty, Staff and Students Publications

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro …

Nanocurcumin Combined With Insulin Alleviates Diabetic Kidney Disease Through P38/P53 Signaling Axis, Raghu Ganugula, Nikhil K Nuthalapati, Subhash Dwivedi, Dianxiong Zou, Meenakshi Arora, Richard Friend, David Sheikh-Hamad, Rita Basu, M N V Ravi Kumar

Faculty, Staff and Students Publications

Treatments for diabetic kidney disease (DKD) mainly focus on managing hyperglycemia and hypertension, but emerging evidence suggests that inflammation also plays a role in the pathogenesis of DKD. This 10-week study evaluated the efficacy of daily oral nanoparticulate-curcumin (nCUR) together with long-acting insulin (INS) to treat DKD in a rodent model. Diabetic rats were dosed with unformulated CUR alone, nCUR alone or together with INS, or INS alone. The progression of diabetes was reflected by increases in plasma fructosamine, blood urea nitrogen, creatinine, bilirubin, ALP, and decrease in albumin and globulins. These aberrancies were remedied by nCUR+INS or INS but …

Diversity And Evolution Of Computationally Predicted T Cell Epitopes Against Human Respiratory Syncytial Virus, Jiani Chen, Swan Tan, Vasanthi Avadhanula, Leonard Moise, Pedro A Piedra, Anne S De Groot, Justin Bahl

Faculty, Staff and Students Publications

Human respiratory syncytial virus (RSV) is a major cause of lower respiratory infection. Despite more than 60 years of research, there is no licensed vaccine. While B cell response is a major focus for vaccine design, the T cell epitope profile of RSV is also important for vaccine development. Here, we computationally predicted putative T cell epitopes in the Fusion protein (F) and Glycoprotein (G) of RSV wild circulating strains by predicting Major Histocompatibility Complex (MHC) class I and class II binding affinity. We limited our inferences to conserved epitopes in both F and G proteins that have been experimentally …

The Rsv F P27 Peptide: Current Knowledge, Important Questions, Wanderson Rezende, Hadley E Neal, Rebecca E Dutch, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) remains a leading cause of hospitalizations and death for young children and adults over 65. The worldwide impact of RSV has prioritized the search for an RSV vaccine, with most targeting the critical fusion (F) protein. However, questions remain about the mechanism of RSV entry and RSV F triggering and fusion promotion. This review highlights these questions, specifically those surrounding a cleaved 27 amino acids long peptide within F, p27.

Cell-Type-Specific Aging Clocks To Quantify Aging And Rejuvenation In Neurogenic Regions Of The Brain, Matthew T Buckley, Eric D Sun, Benson M George, Ling Liu, Nicholas Schaum, Lucy Xu, Jaime M Reyes, Margaret A Goodell, Irving L Weissman, Tony Wyss-Coray, Thomas A Rando, Anne Brunet

Faculty, Staff and Students Publications

The diversity of cell types is a challenge for quantifying aging and its reversal. Here we develop 'aging clocks' based on single-cell transcriptomics to characterize cell-type-specific aging and rejuvenation. We generated single-cell transcriptomes from the subventricular zone neurogenic region of 28 mice, tiling ages from young to old. We trained single-cell-based regression models to predict chronological age and biological age (neural stem cell proliferation capacity). These aging clocks are generalizable to independent cohorts of mice, other regions of the brains, and other species. To determine if these aging clocks could quantify transcriptomic rejuvenation, we generated single-cell transcriptomic datasets of neurogenic …

An Overview: The Diversified Role Of Mitochondria In Cancer Metabolism, Yu'e Liu, Yihong Sun, Yadong Guo, Xiaoyun Shi, Xi Chen, Wenfeng Feng, Lei-Lei Wu, Jin Zhang, Shibo Yu, Yi Wang, Yufeng Shi

Faculty, Staff and Students Publications

Mitochondria are intracellular organelles involved in energy production, cell metabolism and cell signaling. They are essential not only in the process of ATP synthesis, lipid metabolism and nucleic acid metabolism, but also in tumor development and metastasis. Mutations in mtDNA are commonly found in cancer cells to promote the rewiring of bioenergetics and biosynthesis, various metabolites especially oncometabolites in mitochondria regulate tumor metabolism and progression. And mutation of enzymes in the TCA cycle leads to the unusual accumulation of certain metabolites and oncometabolites. Mitochondria have been demonstrated as the target for cancer treatment. Cancer cells rely on two main energy …

Integrative Metabolomics And Transcriptomics Analysis Reveals Novel Therapeutic Vulnerabilities In Lung Cancer, Jose Thaiparambil, Jianrong Dong, Sandra L Grimm, Dimuthu Perera, Chandra Shekar R Ambati, Vasanta Putluri, Matthew J Robertson, Tajhal D Patel, Brandon Mistretta, Preethi H Gunaratne, Min P Kim, Jason T Yustein, Nagireddy Putluri, Cristian Coarfa, Randa El-Zein

Faculty, Staff and Students Publications

BACKGROUND: Non-small cell lung cancer (NSCLC) comprises the majority (~85%) of all lung tumors, with lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being the most frequently diagnosed histological subtypes. Multi-modal omics profiling has been carried out in NSCLC, but no studies have yet reported a unique metabolite-related gene signature and altered metabolic pathways associated with LUAD and LUSC.

METHODS: We integrated transcriptomics and metabolomics to analyze 30 human lung tumors and adjacent noncancerous tissues. Differential co-expression was used to identify modules of metabolites that were altered between normal and tumor.

RESULTS: We identified unique metabolite-related gene signatures specific for …

Selective Reprogramming Of Regulatory T Cells In Solid Tumors Can Strongly Enhance Or Inhibit Tumor Growth, Rami Alfar, John V Napoleon, Imrul Shahriar, Richard Finnell, Cole Walchle, Austin Johnson, Philip S Low

Faculty, Staff and Students Publications

Folate receptor delta (FRδ) has been used as a biomarker for regulatory T cells (Tregs), because its expression is limited to Tregs and ovum. Although FRδ is unable to bind folate, we have used molecular docking software to identify a folate congener that binds FRδ with high affinity and have exploited this FRδ-specific ligand to target attached drugs (imaging agents, immune activators, and immune suppressors) specifically to Tregs in murine tumor xenografts. Analysis of treated tumors demonstrates that targeting of a Toll-like receptor 7 agonist inhibits Treg expression of FOXP3, PD-1, CTLA4, and HELIOS, resulting in 40-80% reduction in tumor …

The Small Intestinal Microbiome: Vibing With Intestinal Stem Cells, Victoria Poplaski, Faith Sawyer, Sarah E Blutt

Faculty, Staff and Students Publications

The epithelial lining of the small intestine mediates its absorptive and secretory function and thus is a critical component of human health. Regeneration and renewal of the epithelium is the result of proliferation of intestinal stem cells (ISCs). Many cell types and molecular factors are known to regulate the ability of ISCs to proliferate, including adjacent neighboring epithelial cells and the underlying, supportive stromal cells. The microbiome resides in the lumen of the small intestine and is in close contact with the epithelium. Due to its proximity to ISCs, it has been hypothesized that species within the microbiome have the …

Versican Provides The Provisional Matrix For Uterine Spiral Artery Dilation And Fetal Growth, Yusuke Sagae, Akihito Horie, Akihiro Yanai, Tsutomu Ohara, Baku Nakakita, Yoshimi Kitawaki, Asuka Okunomiya, Hirohiko Tani, Ken Yamaguchi, Junzo Hamanishi, John P Lydon, Takiko Daikoku, Hideto Watanabe, Masaki Mandai

Faculty, Staff and Students Publications

The extracellular matrix (ECM) in the endometrium plays a crucial role in mammalian pregnancy. We have shown that versican secreted from the endometrial epithelium promotes embryo implantation. Versican is a proteoglycan, a major player in the provisional matrix, and versikine, its N-terminal fragment cleaved by ADAMTS proteinases, serves as a bioactive molecule. Here, since versican expression in the placenta was dynamically altered in humans and mice, we investigated the role of versican in pregnancy using uterine-specific Vcan deletion mice (uKO mice) and ADAMTS-resistant versican expressing mice (V1R mice). uKO mice exhibited insufficient spiral artery dilation, followed by fetal growth restriction …

Role Of Adrenomedullin2/ Intermedin In Pregnancy Induced Vascular And Metabolic Adaptation In Mice, Chandra Yallampalli, Ancizar Betancourt, Akansha Mishra, Kathleen A Pennington, Simone Hernandez Ruano, Moises Tacam, Madhu Chauhan

Faculty, Staff and Students Publications

Introduction: Adrenomedullin2 (AM2) shares its receptor with Calcitonin gene related peptide and adrenomedullin with overlapping but distinct biological functions. Goal of this study was to assess the specific role of Adrenomedullin2 (AM2) in pregnancy induced vascular and metabolic adaptation using AM2 knockout mice (AM2 ^−/−).

Method : The AM2 ^−/− mice were successfully generated using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Nuclease Cas nine system. Phenotype of pregnant AM2 ^−/− mice was assessed with respect to its fertility, blood pressure regulation, vascular health and metabolic adaptations and compared to the wild type littermates (AM2 ^+/+).

Results …

Growth And Differentiation Factor 15 (Gdf15) Levels Predict Adverse Respiratory Outcomes In Premature Neonates, Faeq Almudares, Joseph Hagan, Xinpu Chen, Sridevi Devaraj, Bhagavatula Moorthy, Krithika Lingappan

Faculty, Staff and Students Publications

Growth and differentiation factor 15 (GDF15) is a stress-responsive cytokine, and its expression increases during inflammation, hyperoxia, and senescence. Significantly, GDF15 is secreted by the placenta, and maternal levels increase throughout pregnancy. Serum GDF15 level is a promising biomarker for many lung diseases like pulmonary hypertension and pulmonary fibrosis. However, circulating GDF15 levels in preterm infants and their role as a predictor of respiratory outcomes have not been studied. We hypothesized that GDF15 levels would increase with gestational age at birth, and that postnatal GDF15 will be correlated with adverse respiratory outcomes in preterm infants. Scavenged blood samples were retrieved …

Unmasking Barriers In The Delivery Of Preconception Counseling And Contraception Provision For Patients With Type 1 Or Type 2 Diabetes, Layla A Abushamat, Lauren Sayres, Rebecca Jeffers, Chloe Nielsen, Linda A Barbour, Adnin Zaman

Faculty, Staff and Students Publications

No abstract provided.

Transcriptomic Profiles Of Multiple Organ Dysfunction Syndrome Phenotypes In Pediatric Critical Influenza, Tanya Novak, Jeremy Chase Crawford, Georg Hahn, Mark W Hall, Simone A Thair, Margaret M Newhams, Janet Chou, Peter M Mourani, Keiko M Tarquinio, Barry Markovitz, Laura L Loftis, Scott L Weiss, Renee Higgerson, Adam J Schwarz, Neethi P Pinto, Neal J Thomas, Rainer G Gedeit, Ronald C Sanders, Sidharth Mahapatra, Bria M Coates, Natalie Z Cvijanovich, Kate G Ackerman, David W Tellez, Patrick Mcquillen, Stephen C Kurachek, Steven L Shein, Christoph Lange, Paul G Thomas, Adrienne G Randolph

Faculty, Staff and Students Publications

BACKGROUND: Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection.

METHODS: We measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized …

Clinical Characterization Of Data-Driven Diabetes Clusters Of Pediatric Type 2 Diabetes, Mahsan Abbasi, Mustafa Tosur, Marcela Astudillo, Ahmad Refaey, Ashutosh Sabharwal, Maria J Redondo

Faculty, Staff and Students Publications

BACKGROUND: Pediatric Type 2 diabetes (T2D) is highly heterogeneous. Previous reports on adult-onset diabetes demonstrated the existence of diabetes clusters. Therefore, we set out to identify unique diabetes subgroups with distinct characteristics among youth with T2D using commonly available demographic, clinical, and biochemical data.

METHODS: We performed data-driven cluster analysis (K-prototypes clustering) to characterize diabetes subtypes in pediatrics using a dataset with 722 children and adolescents with autoantibody-negative T2D. The six variables included in our analysis were sex, race/ethnicity, age, BMI

RESULTS: We identified five distinct clusters of pediatric T2D, with different features, treatment regimens and risk of diabetes complications: …