Digital Commons Network^™

Nuclear S6k1 Enhances Oncogenic Wnt Signaling By Inducing Wnt/Β-Catenin Transcriptional Complex Formation, Min Gyu Lee, Hwamok Oh, Jong Woo Park, Jueng Soo You, Jeung-Whan Han

Faculty, Staff and Student Publications

Ribosomal protein S6 kinase 1 (S6K1), a key downstream effector of the mammalian target of rapamycin (mTOR), regulates diverse functions, such as cell proliferation, cell growth, and protein synthesis. Because S6K1 was previously known to be localized in the cytoplasm, its function has been mainly studied in the cytoplasm. However, the nuclear localization and function of S6K1 have recently been elucidated and other nuclear functions are expected to exist but remain elusive. Here, we show a novel nuclear role of S6K1 in regulating the expression of the Wnt target genes. Upon activation of the Wnt signaling, S6K1 translocated from the …

Ccl4 Regulates Eosinophil Activation In Eosiccl4 Regulates Eosinophil Activation In Eosinophilic Airway Inflammationnophilic Airway Inflammation, Hanh Hong Chu, Yoshiki Kobayashi, Dan Van Bui, Yasutaka Yun, Linh Manh Nguyen, Akitoshi Mitani, Kensuke Suzuki, Mikiya Asako, Akira Kanda, Hiroshi Iwai

Faculty, Staff and Student Publications

Eosinophilic chronic rhinosinusitis (ECRS) is a refractory airway disease accompanied by eosinophilic inflammation, the mechanisms of which are unknown. We recently found that CCL4/MIP-1β-a specific ligand for CCR5 receptors-was implicated in eosinophil recruitment into the inflammatory site and was substantially released from activated eosinophils. Moreover, it was found in nasal polyps from patients with ECRS, primarily in epithelial cells. In the present study, the role of epithelial cell-derived CCL4 in eosinophil activation was investigated. First, CCL4 expression in nasal polyps from patients with ECRS as well as its role of CCL4 in eosinophilic airway inflammation were investigated in an in …

Research Infrastructure Core Facilities At Research Centers In Minority Institutions: Part I-Research Resources Management, Operation, And Best Practices, Paul B Tchounwou, Mohamad Malouhi, Elizabeth O Ofili, Emma Fernández-Repollet, Daniel F Sarpong, Richard Yanagihara, Renato J Aguilera, Cecilia Ayón, Xiaoxin Chen, Asok Dasmahapatra, Song Gao, Cimona V Hinton, Robert Holt, Vladimir Kolesnichenko, Michael D Powell, Fatima Merchant, Kinfe K Redda, Abiel Roche-Lima, Cecilia M Shikuma, Jacqueline J Stevens, Jose A Torres, Robert T Trotter, James Wachira, Paul Wang, Kristen J Wells, Jason White, Yanyuan Wu

Faculty, Staff and Student Publications

Funded by the National Institutes of Health (NIH), the Research Centers in Minority Institutions (RCMI) Program fosters the development and implementation of innovative research aimed at improving minority health and reducing or eliminating health disparities. Currently, there are 21 RCMI Specialized (U54) Centers that share the same framework, comprising four required core components, namely the Administrative, Research Infrastructure, Investigator Development, and Community Engagement Cores. The Research Infrastructure Core (RIC) is fundamentally important for biomedical and health disparities research as a critical function domain. This paper aims to assess the research resources and services provided and evaluate the best practices in …

Assessing The Mental Health Of Women At The Intersection Of Intimate Partner Violence And Animal Cruelty: Personal And Population Level Risk Factors For Co-Victimization, Alaina M. Beauchamp

Dissertations and Theses (Open Access)

One predictor of intimate partner violence (IPV) occurring in the home is pet abuse. The high prevalence of pet cruelty among IPV relationship can create a significant barrier to seeking help due to the inability to bring the pet or concern for the pet’s wellbeing. This human-animal bond is a more common source of emotional support among victims with experiences of pet abuse, as opposed to women whose pets had not been abused. This study 1) explored the relationship between victims of IPV and their pets, the dynamics and characteristics of situations of co-victimization (i.e., abuse of both a human …

Egfr Is A Master Switch Between Immunosuppressive And Immunoactive Tumor Microenvironment In Inflammatory Breast Cancer, Xiaoping Wang, Takashi Semba, Ganiraju C Manyam, Jing Wang, Shan Shao, Francois Bertucci, Pascal Finetti, Savitri Krishnamurthy, Lan Thi Hanh Phi, Troy Pearson, Steven J Van Laere, Jared K Burks, Evan N Cohen, James M Reuben, Fei Yang, Hu Min, Nicholas Navin, Van Ngu Trinh, Toshiaki Iwase, Harsh Batra, Yichao Shen, Xiang Zhang, Debu Tripathy, Naoto T Ueno

Faculty, Staff and Student Publications

Inflammatory breast cancer (IBC), the most aggressive breast cancer subtype, is driven by an immunosuppressive tumor microenvironment (TME). Current treatments for IBC have limited efficacy. In a clinical trial (NCT01036087), an anti-EGFR antibody combined with neoadjuvant chemotherapy produced the highest pathological complete response rate ever reported in patients with IBC having triple-negative receptor status. We determined the molecular and immunological mechanisms behind this superior clinical outcome. Using novel humanized IBC mouse models, we discovered that EGFR-targeted therapy remodels the IBC TME by increasing cytotoxic T cells and reducing immunosuppressive regulatory T cells and M2 macrophages. These changes were due to …

In Vivo Characterization Of Glutamine Metabolism Identifies Therapeutic Targets In Clear Cell Renal Cell Carcinoma, Akash K Kaushik, Amy Tarangelo, Lindsey K Boroughs, Mukundan Ragavan, Yuanyuan Zhang, Cheng-Yang Wu, Xiangyi Li, Kristen Ahumada, Jui-Chung Chiang, Vanina T Tcheuyap, Faeze Saatchi, Quyen N Do, Cissy Yong, Tracy Rosales, Christina Stevens, Aparna D Rao, Brandon Faubert, Panayotis Pachnis, Lauren G Zacharias, Hieu Vu, Feng Cai, Thomas P Mathews, Giannicola Genovese, Barbara S Slusher, Payal Kapur, Xiankai Sun, Matthew Merritt, James Brugarolas, Ralph J Deberardinis

Faculty, Staff and Student Publications

Targeting metabolic vulnerabilities has been proposed as a therapeutic strategy in renal cell carcinoma (RCC). Here, we analyzed the metabolism of patient-derived xenografts (tumorgrafts) from diverse subtypes of RCC. Tumorgrafts from VHL-mutant clear cell RCC (ccRCC) retained metabolic features of human ccRCC and engaged in oxidative and reductive glutamine metabolism. Genetic silencing of isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2 impaired reductive labeling of tricarboxylic acid (TCA) cycle intermediates in vivo and suppressed growth of tumors generated from tumorgraft-derived cells. Glutaminase inhibition reduced the contribution of glutamine to the TCA cycle and resulted in modest suppression of tumorgraft growth. Infusions with …

Tiam1-Mediated Synaptic Plasticity Underlies Comorbid Depression-Like And Ketamine Antidepressant-Like Actions In Chronic Pain, Qin Ru, Yungang Lu, Ali Bin Saifullah, Francisco A Blanco, Changqun Yao, Juan P Cata, De-Pei Li, Kimberley F Tolias, Lingyong Li

Faculty, Staff and Students Publications

Chronic pain often leads to depression, increasing patient suffering and worsening prognosis. While hyperactivity of the anterior cingulate cortex (ACC) appears to be critically involved, the molecular mechanisms underlying comorbid depressive symptoms in chronic pain remain elusive. T cell lymphoma invasion and metastasis 1 (Tiam1) is a Rac1 guanine nucleotide exchange factor (GEF) that promotes dendrite, spine, and synapse development during brain development. Here, we show that Tiam1 orchestrates synaptic structural and functional plasticity in ACC neurons via actin cytoskeleton reorganization and synaptic N-methyl-d-aspartate receptor (NMDAR) stabilization. This Tiam1-coordinated synaptic plasticity underpins ACC hyperactivity and drives chronic pain-induced depressive-like behaviors. …

Single Cell Rna Sequencing Of The Adult Drosophila Eye Reveals Distinct Clusters And Novel Marker Genes For All Major Cell Types, Kelvin Yeung, Komal Kumar Bollepogu Raja, Yoon-Kyung Shim, Yumei Li, Rui Chen, Graeme Mardon

Faculty, Staff and Students Publications

The adult Drosophila eye is a powerful model system for phototransduction and neurodegeneration research. However, single cell resolution transcriptomic data are lacking for this tissue. We present single cell RNA-seq data on 1-day male and female, 3-day and 7-day old male adult eyes, covering early to mature adult eyes. All major cell types, including photoreceptors, cone and pigment cells in the adult eye were captured and identified. Our data sets identified novel cell type specific marker genes, some of which were validated in vivo. R7 and R8 photoreceptors form clusters that reflect their specific Rhodopsin expression and the specific Rhodopsin …

Lipid-Nanoparticle-Mediated Delivery Of Docetaxel Prodrug For Exploiting Full Potential Of Gold Nanoparticles In The Treatment Of Pancreatic Cancer, Abdulaziz Alhussan, Nolan Jackson, Sarah Eaton, Nancy Dos Santos, Ingrid Barta, Josh Zaifman, Sam Chen, Yuen Yi C Tam, Sunil Krishnan, Devika B Chithrani

Faculty, Staff and Student Publications

Current chemoradiation therapy suffers from normal tissue toxicity. Thus, we are proposing incorporating gold nanoparticles (GNPs) and docetaxel (DTX), as they have shown very promising synergetic radiosensitization effects. Here, we explored the effect of a DTX prodrug encapsulated in lipid nanoparticles (LNP_DTX-P) on GNP uptake in pancreatic cancer models in vitro and in vivo. For the in vitro experiment, a pancreatic cancer cell line, MIA PaCa-2, was cultured and dosed with 1 nM GNPs and 45 nM free DTX or an equivalent dose of LNP_DTX-P. For the in vivo experiment, MIA PaCa-2 cells were implanted subcutaneously …

Neuronal Signal-Regulatory Protein Alpha Drives Microglial Phagocytosis By Limiting Microglial Interaction With Cd47 In The Retina, Danye Jiang, Courtney A Burger, Viktor Akhanov, Justine H Liang, Robert D Mackin, Nicholas E Albrecht, Pilar Andrade, Dorothy P Schafer, Melanie A Samuel

Center on Aging Staff Publications

Microglia utilize their phagocytic activity to prune redundant synapses and refine neural circuits during precise developmental periods. However, the neuronal signals that control this phagocytic clockwork remain largely undefined. Here, we show that neuronal signal-regulatory protein alpha (SIRPα) is a permissive cue for microglial phagocytosis in the developing murine retina. Removal of neuronal, but not microglial, SIRPα reduced microglial phagocytosis, increased synpase numbers, and impaired circuit function. Conversely, prolonging neuronal SIRPα expression extended developmental microglial phagocytosis. These outcomes depended on the interaction of presynaptic SIRPα with postsynaptic CD47. Global CD47 deficiency modestly increased microglial phagocytosis, while CD47 overexpression reduced it. …

Defining Cellular Population Dynamics At Single-Cell Resolution During Prostate Cancer Progression, Alexandre A Germanos, Sonali Arora, Ye Zheng, Erica T Goddard, Ilsa M Coleman, Anson T Ku, Scott Wilkinson, Hanbing Song, Nicholas J Brady, Robert A Amezquita, Michael Zager, Annalysa Long, Yu Chi Yang, Jason H Bielas, Raphael Gottardo, David S Rickman, Franklin W Huang, Cyrus M Ghajar, Peter S Nelson, Adam G Sowalsky, Manu Setty, Andrew C Hsieh

Faculty, Staff and Student Publications

Advanced prostate malignancies are a leading cause of cancer-related deaths in men, in large part due to our incomplete understanding of cellular drivers of disease progression. We investigate prostate cancer cell dynamics at single-cell resolution from disease onset to the development of androgen independence in an in vivo murine model. We observe an expansion of a castration-resistant intermediate luminal cell type that correlates with treatment resistance and poor prognosis in human patients. Moreover, transformed epithelial cells and associated fibroblasts create a microenvironment conducive to pro-tumorigenic immune infiltration, which is partially androgen responsive. Androgen-independent prostate cancer leads to significant diversification of …

Mir21 Modulates The Hippo Signaling Pathway Via Interference With Pp2a Bβ To Inhibit Trophoblast Invasion And Cause Preeclampsia, Mingyu Hu, Yangxi Zheng, Jiujiang Liao, Li Wen, Juan Cheng, Jiayu Huang, Biao Huang, Li Lin, Yao Long, Yue Wu, Xuan Ye, Yong Fu, Hongbo Qi, Philip N Baker, Chao Tong

Faculty, Staff and Student Publications

Preeclampsia (PE) is a pregnancy-specific disorder attributed to deficient extravillous trophoblast (EVT) invasion into the uterus, but the mechanism of EVT invasion remains unclear. In this study, we found significantly elevated expression of microRNA 21 (miR21), which negatively regulates trophoblast invasion and migration, in preeclamptic placentae. Whole-genome RNA sequencing revealed that PPP2R2B, which encodes PP2A Bβ, and the Hippo pathway are downstream targets of miR21. The effects of miR21 on trophoblast mobility were abolished in LATS1T1079A/S909A and YAP-5SA mutants. Moreover, we found that PP2A Bβ dephosphorylates LATS1 via direct protein-protein interactions and thus modulates the phosphorylation and subcellular distribution …

Egfr-Phosphorylated Gdh1 Harmonizes With Rsk2 To Drive Creb Activation And Tumor Metastasis In Egfr-Activated Lung Cancer, Jihoon Kang, Jaemoo Chun, Jung Seok Hwang, Chaoyun Pan, Jie Li, Austin C Boese, Isabelle Young, Courteney M Malin, Yibin Kang, Don L Gibbons, Gabriel Sica, Haian Fu, Suresh S Ramalingam, Lingtao Jin, Sumin Kang

Faculty, Staff and Student Publications

The cancer metastasis process involves dysregulated oncogenic kinase signaling, but how this orchestrates metabolic networks and signal cascades to promote metastasis is largely unclear. Here we report that inhibition of glutamate dehydrogenase 1 (GDH1) and ribosomal S6 kinase 2 (RSK2) synergistically attenuates cell invasion, anoikis resistance, and immune escape in lung cancer and more evidently in tumors harboring epidermal growth factor receptor (EGFR)-activating or EGFR inhibitor-resistant mutations. Mechanistically, GDH1 is activated by EGFR through phosphorylation at tyrosine 135 and, together with RSK2, enhances the cAMP response element-binding protein (CREB) activity via CaMKIV signaling, thereby promoting metastasis. Co-targeting RSK2 and GDH1 …

Gabapentin Disrupts Binding Of Perlecan To The Α 2Δ1 Voltage Sensitive Calcium Channel Subunit And Impairs Skeletal Mechanosensation, Perla C Reyes Fernandez, Christian S Wright, Adrianna N Masterson, Xin Yi, Tristen V Tellman, Andrei Bonteanu, Katie Rust, Megan L Noonan, Kenneth E White, Karl J Lewis, Uma Sankar, Julia M Hum, Gregory Bix, Danielle Wu, Alexander G Robling, Rajesh Sardar, Mary C Farach-Carson, William R Thompson

Faculty, Staff and Student Publications

Our understanding of how osteocytes, the principal mechanosensors within bone, sense and perceive force remains unclear. Previous work identified "tethering elements" (TEs) spanning the pericellular space of osteocytes and transmitting mechanical information into biochemical signals. While we identified the heparan sulfate proteoglycan perlecan (PLN) as a component of these TEs, PLN must attach to the cell surface to induce biochemical responses. As voltage-sensitive calcium channels (VSCCs) are critical for bone mechanotransduction, we hypothesized that PLN binds the extracellular α2δ1 subunit of VSCCs to couple the bone matrix to the osteocyte membrane. Here, we showed co-localization of PLN and α2δ1 along …

Place Cells Dynamically Refine Grid Cell Activities To Reduce Error Accumulation During Path Integration In A Continuous Attractor Model, Jose A Fernandez-Leon, Ahmet Kerim Uysal, Daoyun Ji

Faculty, Staff and Students Publications

Navigation is one of the most fundamental skills of animals. During spatial navigation, grid cells in the medial entorhinal cortex process speed and direction of the animal to map the environment. Hippocampal place cells, in turn, encode place using sensory signals and reduce the accumulated error of grid cells for path integration. Although both cell types are part of the path integration system, the dynamic relationship between place and grid cells and the error reduction mechanism is yet to be understood. We implemented a realistic model of grid cells based on a continuous attractor model. The grid cell model was …

Human Rabies - Texas, 2021, Dawn Blackburn, Faisal S Minhaj, Roukaya Al Hammoud, Lillian Orciari, Jael Miller, Trevor Maness, Jon Stewart, Brittany Singletary, Elvia Ledezma, Misti Ellsworth, Andrea Carlo-Angleró, Michael Niezgoda, Crystal M Gigante, Agam K Rao, Panayampalli S Satheshkumar, Gloria P Heresi, Amanda Kieffer, Ryan M Wallace

Faculty, Staff and Student Publications

In late August 2021, a boy aged 7 years was bitten by a bat while he was playing outside his apartment home in Medina County, Texas. He informed his parents; however, no rabies postexposure prophylaxis (PEP) was sought because there were no visible bite marks, and the family was unaware that contact with a bat, including in the absence of visible bite marks, might cause rabies. Approximately 2 months later, the child was hospitalized for altered mental status, seizures, and hypersalivation and ultimately received a diagnosis of rabies. Experimental therapies were attempted; however, the child died 22 days after symptom …

An Elf4 Hypomorphic Variant Results In Nk Cell Deficiency, Sandra Andrea Salinas, Emily M Mace, Matilde I Conte, Chun Shik Park, Yu Li, Joshua I Rosario-Sepulveda, Sanjana Mahapatra, Emily K Moore, Evelyn R Hernandez, Ivan K Chinn, Abigail E Reed, Barclay J Lee, Alexander Frumovitz, Richard A Gibbs, Jennifer E Posey, Lisa R Forbes Satter, Akaluck Thatayatikom, Eric J Allenspach, Theodore G Wensel, James R Lupski, H Daniel Lacorazza, Jordan S Orange

Faculty, Staff and Students Publications

NK cell deficiencies (NKD) are a type of primary immune deficiency in which the major immunologic abnormality affects NK cell number, maturity, or function. Since NK cells contribute to immune defense against virally infected cells, patients with NKD experience higher susceptibility to chronic, recurrent, and fatal viral infections. An individual with recurrent viral infections and mild hypogammaglobulinemia was identified to have an X-linked damaging variant in the transcription factor gene ELF4. The variant does not decrease expression but disrupts ELF4 protein interactions and DNA binding, reducing transcriptional activation of target genes and selectively impairing ELF4 function. Corroborating previous murine models …

Targeting Tmem205 Mediated Drug Resistance In Ovarian Clear Cell Carcinoma Using Oncolytic Virus, Uksha Saini, Brentley Q Smith, Kalpana Deepa Priya Dorayappan, Ji Young Yoo, G Larry Maxwell, Balveen Kaur, Ikuo Konishi, David O'Malley, David E Cohn, Karuppaiyah Selvendiran

Faculty, Staff and Student Publications

BACKGROUND: Ovarian clear cell carcinoma (OCCC) accounts for approximately 8-10% of epithelial ovarian cancers in the United States. Although it is rare, OCCC usually presents with treatment challenges and the overall prognosis is far worse than high grade serous ovarian cancer HGSOC. The objective of this study was to examine the therapeutic relevance of combining oncolytic virus with cisplatin for ovarian cancer clear cell carcinoma (OCCC).

RESULTS: We identified that TMEM205, a recently discovered transmembrane protein, contributes to chemoresistance in OCCC cells via the exosomal pathway. Mechanistically, TMEM205 undergoes ligand-independent constitutive endocytosis and co-localizes with Rab11 to contribute to the …

A Gbd 2019 Study Of Health And Sustainable Development Goal Gains And Forecasts To 2030 In Spain, Jeffrey V Lazarus, Alberto Ortiz, Stefanos Tyrovolas, Esteve Fernández, Danielle Guy, Trenton M White, Rui Ma, Simon I Hay, Mohsen Naghavi, Joan B Soriano, Gbd 2019 Spain Collaborators

Faculty, Staff and Student Publications

This study aimed to report mortality, risk factors, and burden of diseases in Spain. The Global Burden of Disease, Injuries, and Risk Factors 2019 estimates the burden due to 369 diseases, injuries, and impairments and 87 risk factors and risk factor combinations. Here, we detail the updated Spain 1990-2019 burden of disease estimates and project certain metrics up to 2030. In 2019, leading causes of death were ischaemic heart disease, stroke, chronic obstructive pulmonary disease, Alzheimer's disease, and lung cancer. Main causes of disability adjusted life years (DALYs) were ischaemic heart disease, diabetes, lung cancer, low back pain, and stroke. …

Heavy Metals In Four Marine Fish And Shrimp Species From A Subtropical Coastal Area: Accumulation And Consumer Health Risk Assessment, Mohammad Belal Hossain, Nurer Zaman Bhuiyan, Abul Kasem, Md Kamal Hossain, Salma Sultana, As-Ad Ujjaman Nur, Jimmy Yu, Mohammed Fahad Albeshr, Takaomi Arai

Faculty, Staff and Student Publications

Trace-element or heavy-metal pollution has emerged as a serious concern in terms of both environmental and human health issues. This study measured six trace and toxic heavy metals (Pb, Cd, Cr, Ni, Cu, and Zn) in four marine fish and shrimp species to assess their accumulation levels and evaluate the risks to human health. The mean concentrations of the metals in fish and shrimp species (Labeo bata, Sillaginopsis panijus, Platycepalus fuscus, and Penaeus monodon) followed the decreasing order of Zn (40.8 ± 9.7 μg/g) > Cu (17.8 ± 7.1 μg/g) > Pb (6.2 ± 1.8 μg/g) > Ni (0.4 ± 0.3 μg/g) > Cd …

The Rheumatoid Arthritis Drug Auranofin Lowers Leptin Levels And Exerts Antidiabetic Effects In Obese Mice, Aaron R Cox, Peter M Masschelin, Pradip K Saha, Jessica B Felix, Robert Sharp, Zeqin Lian, Yan Xia, Natasha Chernis, David A Bader, Kang Ho Kim, Xin Li, Jun Yoshino, Xin Li, Gang Li, Zheng Sun, Huaizhu Wu, Cristian Coarfa, David D Moore, Samuel Klein, Kai Sun, Sean M Hartig

Faculty, Staff and Student Publications

Low-grade, sustained inflammation in white adipose tissue (WAT) characterizes obesity and coincides with type 2 diabetes mellitus (T2DM). However, pharmacological targeting of inflammation lacks durable therapeutic effects in insulin-resistant conditions. Through a computational screen, we discovered that the FDA-approved rheumatoid arthritis drug auranofin improved insulin sensitivity and normalized obesity-associated abnormalities, including hepatic steatosis and hyperinsulinemia in mouse models of T2DM. We also discovered that auranofin accumulation in WAT depleted inflammatory responses to a high-fat diet without altering body composition in obese wild-type mice. Surprisingly, elevated leptin levels and blunted beta-adrenergic receptor activity achieved by leptin receptor deletion abolished the antidiabetic …

Expression Of P-Stat3 And C-Myc Correlates With P2-Hnf4Α Expression In Nonalcoholic Fatty Liver Disease (Nafld), Mamoun Younes, Lin Zhang, Baharan Fekry, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

We studied the expression of two hepatocyte nuclear factor 4 alpha (HNF4α) isoforms, p-STAT3. and c-Myc in 49 consecutive liver biopsies with nonalcoholic fatty liver disease (NAFLD) using immunohistochemistry. All 49 biopsies (100%) were positive for nuclear expression of P1-HNF4α. Twenty-eight (57%) cases were positive for P2-HNF4α, 6 (12%) were positive for p-STAT3 and 5 (10%) were positive for c-Myc. All 6 (100%) p-STAT3-positive cases were also positive for P2-HNF4α (p = 0.03). p-STAT3-positive cases were more likely to be positive for c-Myc (67% vs. 2%, p = 0.0003). Four cases were positive for P2-HNF4α, p-STAT3 and c-Myc. p-STAT3 …

A Unified Model Of Age-Related Cardiovascular Disease, Michael Fossel, Joe Bean, Nina Khera, Mikhail G Kolonin

Faculty, Staff and Student Publications

Despite progress in biomedical technologies, cardiovascular disease remains the main cause of mortality. This is at least in part because current clinical interventions do not adequately take into account aging as a driver and are hence aimed at suboptimal targets. To achieve progress, consideration needs to be given to the role of cell aging in disease pathogenesis. We propose a model unifying the fundamental processes underlying most age-associated cardiovascular pathologies. According to this model, cell aging, leading to cell senescence, is responsible for tissue changes leading to age-related cardiovascular disease. This process, occurring due to telomerase inactivation and telomere attrition, …

Modulation Of Sirtuins During Monolayer Chondrocyte Culture Influences Cartilage Regeneration Upon Transfer To A 3d Culture Environment, Hannah K Heywood, Stephen D Thorpe, Renos M Jeropoulos, Paul W Caton, David A Lee

Faculty, Staff and Student Publications

This study examined the role of sirtuins in the regenerative potential of articular chondrocytes. Sirtuins (SIRT1-7) play a key role in regulating cartilage homeostasis. By inhibiting pro-inflammatory pathways responsible for cartilage degradation and promoting the expression of key matrix components, sirtuins have the potential to drive a favourable balance between anabolic and catabolic processes critical to regenerative medicine. When subjected to osmolarity and glucose concentrations representative of the in vivo niche, freshly isolated bovine chondrocytes exhibited increases in SIRT1 but not SIRT3 gene expression. Replicating methods adopted for the in vitro monolayer expansion of chondrocytes for cartilage regenerative therapies, we …

The Integrative Conjugative Element Icespym92 Contributes To Pathogenicity Of Emergent Antimicrobial-Resistant Emm92 Group A Streptococcus, Ji-Sun Lee, Michael W Lero, Jose Mercado-Matos, Sha Zhu, Minjeong Jo, Claire E Tocheny, Jennifer S Morgan, Leslie M Shaw

Faculty, Staff and Student Publications

Despite the strong association of the insulin/insulin-like growth factor (IGF) signaling (IIS) pathway with tumor initiation, recurrence, and metastasis, the mechanism by which this pathway regulates cancer progression is not well understood. Here, we report that IIS supports breast cancer stem cell (CSC) self-renewal in an IRS2-phosphatidylinositol 3-kinase (PI3K)-dependent manner that involves the activation and stabilization of MYC. IRS2-PI3K signaling enhances MYC expression through the inhibition of GSK3β activity and suppression of MYC phosphorylation on threonine 58, thus reducing proteasome-mediated degradation of MYC and sustaining active pS62-MYC function. A stable T58A-Myc mutant rescues CSC function in Irs2−/− cells, supporting …

Popdc1 Scaffolds A Complex Of Adenylyl Cyclase 9 And The Potassium Channel Trek-1 In Heart, Tanya A Baldwin, Yong Li, Autumn N Marsden, Susanne Rinné, Anibal Garza-Carbajal, Roland F R Schindler, Musi Zhang, Mia A Garcia, Venugopal Reddy Venna, Niels Decher, Thomas Brand, Carmen W Dessauer

Faculty, Staff and Student Publications

The establishment of macromolecular complexes by scaffolding proteins is key to the local production of cAMP by anchored adenylyl cyclase (AC) and the subsequent cAMP signaling necessary for cardiac functions. We identify a novel AC scaffold, the Popeye domain-containing (POPDC) protein. The POPDC family of proteins is important for cardiac pacemaking and conduction, due in part to their cAMP-dependent binding and regulation of TREK-1 potassium channels. We show that TREK-1 binds the AC9:POPDC1 complex and copurifies in a POPDC1-dependent manner with AC9 activity in heart. Although the AC9:POPDC1 interaction is cAMP-independent, TREK-1 association with AC9 and POPDC1 is reduced upon …

Identification Of Acenkps, A Committed Common Progenitor Population Of The Ilc1 And Nk Cell Continuum, Noe Rodriguez-Rodriguez, Paula A Clark, Mayuri Gogoi, Ana C F Ferreira, Bernhard Kerscher, Alastair Crisp, Helen E Jolin, Jane E Murphy, Meera Sivasubramaniam, Luisa Pedro, Jennifer A Walker, Morgan W D Heycock, Jacqueline D Shields, Jillian L Barlow, Andrew N J Mckenzie

Faculty, Staff and Student Publications

The development of innate lymphoid cell (ILC) transcription factor reporter mice has shown a previously unexpected complexity in ILC hematopoiesis. Using novel polychromic mice to achieve higher phenotypic resolution, we have characterized bone marrow progenitors that are committed to the group 1 ILC lineage. These common ILC1/NK cell progenitors (ILC1/NKP), which we call "aceNKPs", are defined as lineage-Id2+IL-7Rα+CD25-α4β7-NKG2A/C/E+Bcl11b-. In vitro, aceNKPs differentiate into group 1 ILCs, including NK-like cells that express Eomes without the requirement for IL-15, and produce IFN-γ and perforin upon IL-15 stimulation. Following reconstitution of Rag2-/-Il2rg-/- hosts, aceNKPs give rise to a spectrum of mature ILC1/NK cells …

Ic 013 Guide To University Of Texas School Of Public Health Records, 1970-1995; 1967-2008, University Of Texas Health Science Center At Houston. School Of Public Health

Institutional Finding Aids

The University of Texas School of Public Health (SPH) records contains records from the School, as well as related programs and topics. The majority of the collection is made up of copies of the SPH Calendar from 1978-1983 and the SPH Catalog from 1971-1995. See more at IC 013.

Activity Disruption Causes Degeneration Of Entorhinal Neurons In A Mouse Model Of Alzheimer’S Circuit Dysfunction, Rong Zhao, Stacy D Grunke, Caleb A Wood, Gabriella A Perez, Melissa Comstock, Ming-Hua Li, Anand K Singh, Kyung-Won Park, Joanna L Jankowsky

Faculty, Staff and Students Publications

Neurodegenerative diseases are characterized by selective vulnerability of distinct cell populations; however, the cause for this specificity remains elusive. Here, we show that entorhinal cortex layer 2 (EC2) neurons are unusually vulnerable to prolonged neuronal inactivity compared with neighboring regions of the temporal lobe, and that reelin + stellate cells connecting EC with the hippocampus are preferentially susceptible within the EC2 population. We demonstrate that neuronal death after silencing can be elicited through multiple independent means of activity inhibition, and that preventing synaptic release, either alone or in combination with electrical shunting, is sufficient to elicit silencing-induced degeneration. Finally, we …

Selective Vulnerability Of The Intermediate Retinal Capillary Plexus Precedes Retinal Ganglion Cell Loss In Ocular Hypertension, Priyamvada M Pitale, Guofu Shen, Rohini R Sigireddi, Maria Polo-Prieto, Yong H Park, Solomon E Gibson, Peter D Westenskow, Roomasa Channa, Benjamin J Frankfort

Faculty, Staff and Students Publications

Introduction: Glaucoma, a disease of retinal ganglion cell (RGC) injury and potentially devastating vision loss, is associated with both ocular hypertension (OHT) and reduced ocular blood flow. However, the relationship between OHT and retinal capillary architecture is not well understood. In this project, we studied microvasculature damage in mice exposed to mild levels of induced OHT.

Methods: Mild OHT was induced with the microbead model for 2 weeks. At this time point, some retinas were immunostained with CD31 (endothelium), Collagen IV (basement membrane), and RBPMS (RGCs) for z-stack confocal microscopy. We processed these confocal images to distinguish the three retinal …