Medicine and Health Sciences Commons^™

Association Of Smoking With Total Oxidant And Antioxidant Levels In Breast Milk, Nesibe Yildiz, Adnan Yilmaz

Makara Journal of Health Research

Background: Breast milk is a natural food that contains all the fluids, energy, and nutrients necessary for the optimum growth and development of newborns. Smoking is a public health problem that has harmful effects on the mother and baby. This study aimed to examine the association of exposure to smoking with total oxidant status (TOS) and total antioxidant status (TAS) in breast milk.

Methods: Healthy mothers without any health problems during their pregnancy and lactation periods were selected as subjects. Eighty-eight milk samples (44 in the smoking group and 44 in the nonsmoking group) were examined. TOS and …

Kras Inhibitor That Simultaneously Inhibits Nucleotide Exchange Activity And Effector Engagement, Cynthia V Pagba, Amit K Gupta, Ali K Naji, Dharini Van Der Hoeven, Kelly Churion, Xiaowen Liang, Jacob Jakubec, Magnus Hook, Yan Zuo, Marisela Martinez De Kraatz, Jeffrey A Frost, Alemayehu A Gorfe

Student and Faculty Publications

We describe a small molecule ligand ACA-14 (2-hydroxy-5-{[(2-phenylcyclopropyl) carbonyl] amino} benzoic acid) as an initial lead for the development of direct inhibitors of KRAS, a notoriously difficult anticancer drug target. We show that the compound binds to KRAS near the switch regions with affinities in the low micromolar range and exerts different effects on KRAS interactions with binding partners. Specifically, ACA-14 impedes the interaction of KRAS with its effector Raf and reduces both intrinsic and SOS-mediated nucleotide exchange rates. Likely as a result of these effects, ACA-14 inhibits signal transduction through the MAPK pathway in cells expressing mutant KRAS and …

Secretion Of Salivary Proteins And Their Interactions, Karla Tonelli Bicalho Crosara

Electronic Thesis and Dissertation Repository

Saliva’s clinical application for disease diagnosis and monitoring is limited by incomplete knowledge of salivary protein interactions, the effect of stimulation on the salivary proteome, and if these factors impact protein identification. This thesis expands knowledge of the salivary interactome and effects of stimulation intensity and duration on parotid saliva’s proteome. First, previous in vitro studies identified 43 proteins in the histatin 1-protein network and demonstrated histatin 1’s increased stability in whole saliva when interacting with amylase. We hypothesized that protein-protein-interaction databases could enlarge the histatin 1-protein network. A comprehensive histatin 1-protein network was created using STRING database, merging previous …

In Silico Identification Of A Β2-Adrenoceptor Allosteric Site That Selectively Augments Canonical Β2ar-Gs Signaling And Function, Sushrut D Shah, Christoffer Lind, Francesco De Pascali, Raymond B Penn, Alexander D Mackerell, Deepak A Deshpande

Department of Biochemistry and Molecular Biology Faculty Papers

Activation of β2-adrenoceptors (β2ARs) causes airway smooth muscle (ASM) relaxation and bronchodilation, and β2AR agonists (β-agonists) are front-line treatments for asthma and other obstructive lung diseases. However, the therapeutic efficacy of β-agonists is limited by agonist-induced β2AR desensitization and noncanonical β2AR signaling involving β-arrestin that is shown to promote asthma pathophysiology. Accordingly, we undertook the identification of an allosteric site on β2AR that could modulate the activity of β-agonists to overcome these limitations. We employed the site identification by ligand competitive saturation (SILCS) computational method to comprehensively map the entire 3D structure of in silico-generated β2AR intermediate conformations and identified …

Computer-Aided Drug Discovery For Helicobacter Pylori, Nicole Ann Vita

Theses and Dissertations (ETD)

Helicobacter pylori is a high-priority drug-resistant pathogen and is currently the only bacteria considered to be a class I carcinogen and there is a critical need to identify novel chemical matter to treat H. pylori infections. Hp is responsible for greater than 60% of gastric cancer related deaths and 89% of all gastric cancer morbidities. In a previous study, our lab identified novel Hp thienopyrmidine inhibitors that target respiratory complex I, an essential enzyme in respiration. Respiratory complex I is a large asymmetric multidomain and membrane bound enzyme and due to these innate features, it is not practical for biophysical …

Unilateral ‘Crazy-Paving’ Pattern: An Exceptional Presentation Of Squamous Cell Carcinoma Of The Lung, Sumeera Banday, Shamim U Khan, Sabina Khan, Surinderpal S Anand, Ashok Shah

Faculty and Staff Publications

The 'crazy-paving' pattern on high resolution computed tomography (HRCT) is a distinct imaging appearance that is still considered to be a radiological hallmark of pulmonary alveolar proteinosis. However, since its first description about three decades ago, more than 40 different clinical entities presenting as 'crazy-paving' patterns have been documented. This rather remarkable but uncommon imaging appearance is now considered to be a non-specific manifestation. A 62-year-old male referred for evaluation of productive cough, breathlessness and fever presented with 'crazy-paving' pattern on HRCT. Endobronchial biopsy done on presentation was consistent with the diagnosis of squamous cell carcinoma. This report highlights this …

Right Ventricular Energetic Biomarkers From 4d Flow Cmr Are Associated With Exertional Capacity In Pulmonary Arterial Hypertension, Xiaodan Zhao, Shuang Leng, Ru-San Tan, Ping Chai, Tee Joo Yeo, Jennifer Ann Bryant, Lynette L S Teo, Marielle V Fortier, Wen Ruan, Ting Ting Low, Ching Ching Ong, Shuo Zhang, Rob J Van Der Geest, John C Allen, Marina Hughes, Pankaj Garg, Teng Hong Tan, James W Yip, Ju Le Tan, Liang Zhong

Student and Faculty Publications

BACKGROUND: Cardiovascular magnetic resonance (CMR) offers comprehensive right ventricular (RV) evaluation in pulmonary arterial hypertension (PAH). Emerging four-dimensional (4D) flow CMR allows visualization and quantification of intracardiac flow components and calculation of phasic blood kinetic energy (KE) parameters but it is unknown whether these parameters are associated with cardiopulmonary exercise test (CPET)-assessed exercise capacity, which is a surrogate measure of survival in PAH. We compared 4D flow CMR parameters in PAH with healthy controls, and investigated the association of these parameters with RV remodelling, RV functional and CPET outcomes.

METHODS: PAH patients and healthy controls from two centers were prospectively …

Clinicopathological And Prognostic Significance Of Cxcr4 Expression In Osteosarcoma: A Meta-Analysis, I Gusti Ngurah Ananda Wira Kusuma, Grace Yulia Alphani Yapson, John Nolan, I Gede Eka Wiratnaya, I Gede Putu Supadmanaba

BioMedicine

Background: The C-X-C Motif Chemokine Receptor (CXCR4) is an oncogene that has been widely studied and associated with worse clinicopathological features and prognosis outcomes in many types of cancer. Besides that, significance of CXCR4 expression on clinicopathological features and prognostic factors in osteosarcoma (OS) requires further validation.

Aim: We conducted a meta-analysis to evaluate the association between positive CXCR4 expression with clinicopathological features and prognosis in OS.

Methods: Literature searches on Pubmed, Cochrane Library, and Web of Science were conducted systematically up to December 2021 to find relevant references. The effects of CXCR4 expression on clinicopathological characteristics and prognostic were …

Terminase Subunits From The Pseudomonas-Phage E217, Ravi K Lokareddy, Chun-Feng David Hou, Steven G Doll, Fenglin Li, Richard E Gillilan, Francesca Forti, David S Horner, Federica Briani, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

Pseudomonas phages are increasingly important biomedicines for phage therapy, but little is known about how these viruses package DNA. This paper explores the terminase subunits from the Myoviridae E217, a Pseudomonas-phage used in an experimental cocktail to eradicate P. aeruginosa in vitro and in animal models. We identified the large (TerL) and small (TerS) terminase subunits in two genes ∼58 kbs away from each other in the E217 genome. TerL presents a classical two-domain architecture, consisting of an N-terminal ATPase and C-terminal nuclease domain arranged into a bean-shaped tertiary structure. A 2.05 Å crystal structure of the C-terminal domain revealed …

The Detection Of Periodic Reemergence Events Of Sars-Cov-2 Delta Strain In Communities Dominated By Omicron, Claire E. Westcott, Kevin J. Sokoloski, Eric C. Rouchka, Julia H. Chariker, Rochelle H. Holm, Ray A. Yeager, Joseph B. Moore Iv, Erin M. Elliott, Daymond Talley, Aruni Bhatnagar

Faculty Scholarship

Despite entering an endemic phase, SARS-CoV-2 remains a significant burden to public health across the global community. Wastewater sampling has consistently proven utility to understanding SARS-CoV-2 prevalence trends and genetic variation as it represents a less biased assessment of the corresponding communities. Here, we report that ongoing monitoring of SARS-CoV-2 genetic variation in samples obtained from the wastewatersheds of the city of Louisville in Jefferson county Kentucky has revealed the periodic reemergence of the Delta strain in the presence of the presumed dominant Omicron strain. Unlike previous SARS-CoV-2 waves/emergence events, the Delta reemergence events were geographically restricted in the community …

Integrating Genomic Information With Tumor-Immune Microenvironment In Triple-Negative Breast Cancer, David Otohinoyi, Aditi Kuchi, Jiande Wu, Chindo Hicks

School of Graduate Studies Faculty Publications

Background: the development and progression of triple-negative breast cancer (TNBC) is driven by somatic driver mutations and the tumor-immune microenvironment. To date, data on somatic mutations has not been leveraged and integrated with information on the immune microenvironment to elucidate the possible oncogenic interactions and their potential effects on clinical outcomes. Here, we investigated possible oncogenic interactions between somatic mutations and the tumor-immune microenvironment, and their correlation with patient survival in TNBC. Methods: We performed analysis combining data on 7,875 somatic mutated genes with information on 1,751 immune-modulated genes, using gene-expression data as the intermediate phenotype, and correlated the resulting …

Structure Of The Pre-Mrna Leakage 39-Kda Protein Reveals A Single Domain Of Integrated Zf-C3hc And Rsm1 Modules, Hideharu Hashimoto, Daniel H. Ramirez, Ophélie Lautier, Natalie Pawlak, Günter Blobel, Benoît Palancade, Erik W. Debler

Department of Biochemistry and Molecular Biology Faculty Papers

In Saccharomyces cerevisiae, the pre-mRNA leakage 39-kDa protein (ScPml39) was reported to retain unspliced pre-mRNA prior to export through nuclear pore complexes (NPCs). Pml39 homologs outside the Saccharomycetaceae family are currently unknown, and mechanistic insight into Pml39 function is lacking. Here we determined the crystal structure of ScPml39 at 2.5 Å resolution to facilitate the discovery of orthologs beyond Saccharomycetaceae, e.g. in Schizosaccharomyces pombe or human. The crystal structure revealed integrated zf-C3HC and Rsm1 modules, which are tightly associated through a hydrophobic interface to form a single domain. Both zf-C3HC and Rsm1 modules belong to the Zn-containing BIR (Baculovirus IAP …

Effects Of Cannabinoids On Ligand-Gated Ion Channels, Murat Oz, Keun-Hang Susan Yang, Mohamed Omer Mahgoub

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Phytocannabinoids such as Δ⁹-tetrahydrocannabinol and cannabidiol, endocannabinoids such as N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, and synthetic cannabinoids such as CP47,497 and JWH-018 constitute major groups of structurally diverse cannabinoids. Along with these cannabinoids, CB1 and CB2 cannabinoid receptors and enzymes involved in synthesis and degradation of endocannabinoids comprise the major components of the cannabinoid system. Although, cannabinoid receptors are known to be involved in anti-convulsant, anti-nociceptive, anti-psychotic, anti-emetic, and anti-oxidant effects of cannabinoids, in recent years, an increasing number of studies suggest that, at pharmacologically relevant concentrations, these compounds interact with several molecular targets including G-protein coupled receptors, ion …

Novel Varienta Related To Protein S And Folate Deficiency In A Female Patient, Alaa Malik, Diana Polania-Villanueva, Manoj Kumar, Jone Garai, Jovanny Zabaleta, Rinku Majumder

Medical Student Research Poster Symposium

Protein S (PS) is a multifunctional protein that exists in a free and bound form in plasma. The free form of PS acts as an anticoagulant in plasma. Traditionally, PS’s role in coagulation is described as a cofactor for Activated Protein C (APC) or Tissue Factor Pathway Inhibitor (TFPI). Both pathways result in decreased thrombin generation and ultimately reduced fibrin formation. Recently, it has been discovered that PS directly inhibits Factor IXa (FIXa), and thereby directly reduces thrombin generation. PS deficiency is a life-threatening condition that can result in an increased risk for developing disseminated intravascular coagulation or venous thromboembolism …

The Effects Of Obesity And Estrogen Based Contraceptive Use On Protein S Levels And Clotting Function In Pre-Menopausal Women, Daniel Ruppert, Alaa Malik, Manoj Kumar, Rinku Majumder

Medical Student Research Poster Symposium

Protein S (PS) is an essential natural anticoagulant whose deficiency is a major contributor to acquired hypercoagulability [1]. Acquired hypercoagulability causes myocardial infarction, stroke, and deep vein thrombosis in millions of individuals [2]. Many factors affect plasma PS level; most prominently, the female hormone estrogen alters PS level by suppressing PS gene transcription via the estrogen receptor α (ERα) [3]. Thus, women who use estrogen-based oral contraceptive agents (OCA) experience a decrease in PS level. This contraceptive-induced PS decrease enhances the risk of thrombosis by 3-fold (4). Decreased plasma PS is also associated with obesity; obesity elevates the risk of …

Viral Small Terminase: A Divergent Structural Framework For A Conserved Biological Function., Ravi K. Lokareddy, Chun-Feng David Hou, Fenglin Li, Ruoyu Yang, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

The genome packaging motor of bacteriophages and herpesviruses is built by two terminase subunits, known as large (TerL) and small (TerS), both essential for viral genome packaging. TerL structure, composition, and assembly to an empty capsid, as well as the mechanisms of ATP-dependent DNA packaging, have been studied in depth, shedding light on the chemo-mechanical coupling between ATP hydrolysis and DNA translocation. Instead, significantly less is known about the small terminase subunit, TerS, which is dispensable or even inhibitory in vitro, but essential in vivo. By taking advantage of the recent revolution in cryo-electron microscopy (cryo-EM) and building upon a …

The Role Of Ubiquitination In Spinal And Bulbar Muscular Atrophy, Medha Sengupta, Anna Pluciennik, Diane E. Merry

Department of Biochemistry and Molecular Biology Faculty Papers

Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative and neuromuscular genetic disease caused by the expansion of a polyglutamine-encoding CAG tract in the androgen receptor (AR) gene. The AR is an important transcriptional regulator of the nuclear hormone receptor superfamily; its levels are regulated in many ways including by ubiquitin-dependent degradation. Ubiquitination is a post-translational modification (PTM) which plays a key role in both AR transcriptional activity and its degradation. Moreover, the ubiquitin-proteasome system (UPS) is a fundamental component of cellular functioning and has been implicated in diseases of protein misfolding and aggregation, including polyglutamine (polyQ) repeat expansion diseases …

Young Transposable Elements Rewired Gene Regulatory Networks In Human And Chimpanzee Hippocampal Intermediate Progenitors, Sruti Patoori, Samantha M Barnada, Christopher Large, John I Murray, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

The hippocampus is associated with essential brain functions, such as learning and memory. Human hippocampal volume is significantly greater than expected compared with that of non-human apes, suggesting a recent expansion. Intermediate progenitors, which are able to undergo multiple rounds of proliferative division before a final neurogenic division, may have played a role in evolutionary hippocampal expansion. To investigate the evolution of gene regulatory networks underpinning hippocampal neurogenesis in apes, we leveraged the differentiation of human and chimpanzee induced pluripotent stem cells into TBR2 (or EOMES)-positive hippocampal intermediate progenitor cells (hpIPCs). We found that the gene networks active in hpIPCs …

Enhanced Membrane Binding Of Oncogenic G Protein Αqq209l Confers Resistance To Inhibitor Ym-254890, Clinita E. Randolph, Morgan B. Dwyer, Jenna L. Aumiller, Alethia J. Dixon, Asuka Inoue, Patrick Osei-Owusu, Philip B. Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

Heterotrimeric G proteins couple activated G protein-coupled receptors (GPCRs) to intracellular signaling pathways. They can also function independently of GPCR activation upon acquiring mutations that prevent GTPase activity and result in constitutive signaling, as occurs with the αqQ209L mutation in uveal melanoma. YM-254890 (YM) can inhibit signaling by both GPCR-activated WT αq and GPCR-independent αqQ209L. Although YM inhibits WT αq by binding to αq-GDP and preventing GDP/GTP exchange, the mechanism of YM inhibition of cellular αqQ209L remains to be fully understood. Here, we show that YM promotes a subcellular redistribution of αqQ209L from the plasma membrane (PM) to the cytoplasm. …

Oral Nanomedicines For Sirna Delivery To Treat Inflammatory Bowel Disease, Jongyoon Shinn, Juyeon Lee, Seon Ah Lee, Seon Ju Lee, Ah Hyun Choi, Jung Seo Kim, Su Jin Kim, Hyo Jin Kim, Cherin Lee, Yejin Kim, Joohyeon Kim, Jonghee Choi, Byungchae Jung, Taeho Kim, Hyeontaek Nam, Hyungjun Kim, Yonghyun Lee

Student and Faculty Publications

RNA interference (RNAi) therapies have significant potential for the treatment of inflammatory bowel diseases (IBD). Although administering small interfering RNA (siRNA) via an oral route is desirable, various hurdles including physicochemical, mucus, and cellular uptake barriers of the gastrointestinal tract (GIT) impede both the delivery of siRNA to the target site and the action of siRNA drugs at the target site. In this review, we first discuss various physicochemical and biological barriers in the GI tract. Furthermore, we present recent strategies and the progress of oral siRNA delivery strategies to treat IBD. Finally, we consider the challenges faced in the …

Turning Nonselective Inhibitors Of Type I Protein Arginine Methyltransferases Into Potent And Selective Inhibitors Of Protein Arginine Methyltransferase 4 Through A Deconstruction-Reconstruction And Fragment-Growing Approach, Giulia Iannelli, Ciro Milite, Nils Marechal, Vincent Cura, Luc Bonnefond, Nathalie Troffer-Charlier, Alessandra Feoli, Donatella Rescigno, Yalong Wang, Alessandra Cipriano, Monica Viviano, Mark T Bedford, Jean Cavarelli, Sabrina Castellano, Gianluca Sbardella

Student and Faculty Publications

Protein arginine methyltransferases (PRMTs) are important therapeutic targets, playing a crucial role in the regulation of many cellular processes and being linked to many diseases. Yet, there is still much to be understood regarding their functions and the biological pathways in which they are involved, as well as on the structural requirements that could drive the development of selective modulators of PRMT activity. Here we report a deconstruction-reconstruction approach that, starting from a series of type I PRMT inhibitors previously identified by us, allowed for the identification of potent and selective inhibitors of PRMT4, which regardless of the low cell …

Isc10, An Inhibitor Of The Smk1 Mapk, Prevents Activation Loop Autophosphorylation And Substrate Phosphorylation Through Separate Mechanisms, Abhimannyu Rimal, Thomas M Swayne, Zeal P Kamdar, Madison A Tewey, Edward Winter

Department of Biochemistry and Molecular Biology Faculty Papers

Many eukaryotic protein kinases are activated by the intramolecular autophosphorylation of activation loop residues. Smk1 is a meiosis-specific mitogen-activated protein kinase (MAPK) in yeast that autophosphorylates its activation loop tyrosine and thereby upregulates catalytic output. This reaction is controlled by an inhibitor, Isc10, that binds the MAPK during meiosis I and an activator, Ssp2, that binds Smk1/Isc10 during meiosis II. Upon completion of the meiotic divisions, Isc10 is degraded, and Smk1 undergoes autophosphorylation to generate the high activity form of the MAPK that controls spore formation. How Isc10 inhibits Smk1 is not clear. Here, we use a bacterial coexpression/reconstitution system …

The Pro-Fibrotic Response To Lens Injury Is Signaled In A Pi3k Isoform-Specific Manner, A. Sue Menko, Janice L. Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The signaling inputs that function to integrate biochemical and mechanical cues from the extracellular environment to alter the wound-repair outcome to a fibrotic response remain poorly understood. Here, using a clinically relevant post-cataract surgery wound healing/fibrosis model, we investigated the role of Phosphoinositide-3-kinase (PI3K) class I isoforms as potential signaling integrators to promote the proliferation, emergence and persistence of collagen I-producing alpha smooth muscle actin (αSMA+) myofibroblasts that cause organ fibrosis. Using PI3K isoform specific small molecule inhibitors, our studies revealed a requisite role for PI3K p110α in signaling the CD44+ mesenchymal leader cell population that we previously identified as …

G Protein-Coupled Receptor Kinase 6 (Grk6) Regulates Insulin Processing And Secretion Via Effects On Proinsulin Conversion To Insulin, Matthew J Varney, Wouter Steyaert, Paul J Coucke, Joris R Delanghe, David E Uehling, Babu Joseph, Richard Marcellus, Rima Al-Awar, Jeffrey L Benovic

Department of Biochemistry and Molecular Biology Faculty Papers

Recent studies identified a missense mutation in the gene coding for G protein-coupled receptor kinase 6 (GRK6) that segregates with type 2 diabetes (T2D). To better understand how GRK6 might be involved in T2D, we used pharmacological inhibition and genetic knockdown in the mouse β-cell line, MIN6, to determine whether GRK6 regulates insulin dynamics. We show inhibition of GRK5 and GRK6 increased insulin secretion but reduced insulin processing while GRK6 knockdown revealed these same processing defects with reduced levels of cellular insulin. GRK6 knockdown cells also had attenuated insulin secretion but enhanced proinsulin secretion consistent with decreased processing. In support …

Mistranslating Trnas Alter The Heat Shock Activation By Hsf1, Rebecca Dib

Undergraduate Student Research Internships Conference

Translation, or the production of protein from an mRNA blueprint, is among the most fundamental processes to life as we know it. tRNAs are essential to accurate translation, as they decode the codons of mRNA and recruit corresponding amino acids. Variant tRNAs with anticodon mutations can decrease translational fidelity by recruiting the incorrect amino acid, an aberrant process known as mistranslation. When proteins are produced with incorrect amino acid sequences, they may misfold. The heat shock response functions to alleviate cellular stress caused by misfolded proteins, either by refolding or targeting misfolded proteins for degradation. Hsf1 acts as a transcriptional …

The Effect Of Type 1 Diabetes On The Metabolic Response To Exercise, Theres Tijo

Undergraduate Student Research Internships Conference

Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder that results in insufficient endogenous insulin production. Regular exercise has numerous health benefits for individuals with T1DM, however, most insulin-dependent diabetics avoid physical activity due to the fear of exercise-induced hypoglycemia (low blood glucose/BG).

The risk of hypoglycemia in this population may be partly due to lower liver glycogen stores which is a major source of blood glucose during exercise. However, the mechanism that leads to lower glycogen stores in T1DM is unknown.

The purpose of this study was to determine the effect of an acute bout of moderate-intensity aerobic exercise …

Subtype-Selective Positive Modulation Of KCa2.3 Channels Increases Cilia Length, Young-Woo Nam, Rajasekharreddy Pala, Naglaa Salem El-Sayed, Denisse Laren-Henriquez, Farideh Amirrad, Grace Yang, Mohammad Asikur Rahman, Razan Orfali, Myles Downey, Keykavous Parang, Surya M. Nauli, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca²⁺-activated potassium (K_Ca2.x) channels are gated exclusively by intracellular Ca²⁺. The activation of K_Ca2.3 channels induces hyperpolarization, which augments Ca²⁺ signaling in endothelial cells. Cilia are specialized Ca²⁺ signaling compartments. Here, we identified compound 4 that potentiates human K_Ca2.3 channels selectively. The subtype selectivity of compound 4 for human K_Ca2.3 over rat K_Ca2.2a channels relies on an isoleucine residue in the HA/HB helices. Positive modulation of K_Ca2.3 channels by compound 4 increased flow-induced Ca²⁺ signaling and cilia length, while negative …

Glucose Uptake By Glut1 In Photoreceptors Is Essential For Outer Segment Renewal And Rod Photoreceptor Survival, Lauren L. Daniele, John Y.S. Han, Ivy S Samuels, Ravikiran Komirisetty, Nikhil Mehta, Jessica L Mccord, Minzhong Yu, Yekai Wang, Kathleen Boesze-Battaglia, Brent A Bell, Jianhai Du, Neal S Peachey, Nancy J. Philp

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Photoreceptors consume glucose supplied by the choriocapillaris to support phototransduction and outer segment (OS) renewal. Reduced glucose supply underlies photoreceptor cell death in inherited retinal degeneration and age-related retinal disease. We have previously shown that restricting glucose transport into the outer retina by conditional deletion of Slc2a1 encoding GLUT1 resulted in photoreceptor loss and impaired OS renewal. However, retinal neurons, glia, and the retinal pigment epithelium play specialized, synergistic roles in metabolite supply and exchange, and the cell-specific map of glucose uptake and utilization in the retina is incomplete. In these studies, we conditionally deleted Slc2a1 in a pan-retinal or …

Screening Tcf19 And Kif18b To Determine Co-Regulation With Mybl1 In Triple Negative Breast Cancer Patient Tissues, Tyra Sharda Ivory

Theses (2016-Present)

The aggressive behavior in triple-negative breast cancer (TNBC) is due to genetic signaling events, which call for the comprehensive analyses of genes differentially regulated in the cancers. Our laboratory previously found that MYBL1 was over-expressed in a fraction of the TNBC, compared to some luminal, and other breast cancer subtypes. The MYBL1 gene is a proto-oncogene that serves as a strong transcriptional activator. The gene is involved in signaling events related to cell cycle signaling, differentiation, proliferation, and apoptosis, all which are differentially regulated in cancers. Because MYBL1 is a transcription regulator, involved in cancer-related mechanisms and differentially expressed in …

Mettl14-Mediated Epitranscriptome Modification Of Mn1 Mrna Promote Tumorigenicity And All-Trans-Retinoic Acid Resistance In Osteosarcoma, Hong-Bo Li, Gang Huang, Jian Tu, Dong-Ming Lv, Qing-Lin Jin, Jun-Kai Chen, Yu-Tong Zou, Dung-Fang Lee, Jing-Nan Shen, Xian-Biao Xie

Student and Faculty Publications

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents. The molecular mechanism behind OS progression and metastasis remains poorly understood, which limits the effectiveness of current therapies. RNA N

METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS), dot blotting, and colorimetric ELISA were used to detect m

FINDINGS: We observed the abundance of m

INTERPRETATION: Our study revealed that METTL14 contributes to OS progression and ATRA resistance as an m

FUNDING: This work was supported by the National Natural Science Foundation of China (Grants 81972510 and 81772864).