Cell and Developmental Biology Commons^™

Alternative Splicing Of Cytoplasmic Polyadenylation Element Binding Protein 2 Is Modulated Via Serine Arginine Splicing Factor 3 In Cancer Metastasis, James T. Deligio, James Thomas Deligio

Theses and Dissertations

Our laboratory delineated a role for alternative pre-mRNA splicing (AS) in triple negative breast cancer (TNBC). We found the translational regulator cytosolic polyadenylation element binding protein 2 (CPEB2) which has two isoforms, CPEB2A and CPEB2B, is alternatively spliced during acquisition of anoikis resistance (AnR) and metastasis. The splicing event which determines the CPEB2 isoform is via inclusion/ exclusion of exon four in the mature mRNA transcript. The loss of CPEB2A with a concomitant increase in CPEB2B is required for TNBC cells to metastasize in vivo. We examined RNAseq profiles of TNBC cells which had CPEB2 isoforms specifically downregulated to …

Using The Frog Epidermis To Uncover Desmosome Function And Regulation In The Developing Embryo, Navaneetha Krishnan Bharathan

Theses and Dissertations

The desmosome is one of the major cell adhesion junctions found in the epithelia, heart, and hair follicle. Described as a “rivet” that hold cells together, it provides these tissues with the integrity to withstand the tremendous forces they face in everyday life. Defects in this junction can lead to devastating diseases where patients are susceptible to skin infections and cardiovascular defects. Limited treatments exist for diseases of the desmosome, and strategies do not target all symptoms. Therefore, delineating the function and regulation of desmosomes is of paramount importance for the development of prevention and treatment strategies. The Xenopus laevis …

Chromodomain Helicase Dna Binding Protein 1 (Chd1) Is Required For Orofacial Development In Xenopus, Brent Wyatt

Theses and Dissertations

Abnormalities affecting orofacial development are some of the most common, expensive, and devastating birth defects. Children born with such defects may experience difficulties with eating, breathing, and speech and in addition, these defects often require multiple surgeries to correct them. Therefore, it is critical to understand how the orofacial region develops in order to better treat and prevent these types of birth defects. Xenopus laevis has emerged as a strong model in which to examine orofacial development and was utilized here to investigate the cellular and molecular mechanisms underlying the complex development of the orofacial region. Retinoic acid is one …

Stat3 In The Regulation Of Brown Adipocyte Differentiation, Marc Cantwell

Theses and Dissertations

Thermogenic fat is a promising target for new therapies in diabetes and obesity. Understanding how thermogenic fat develops is important to develop rational strategies to treat obesity. Previously, we have shown that Tyk2 and STAT3, part of the JAK-STAT pathway, are necessary for proper development of classical brown fat. Using primary preadipocytes isolated from newborn mice we demonstrate that STAT3 is required for differentiation and robust expression of Uncoupling Protein 1. We also confirm that STAT3 is necessary during the early induction stage of differentiation and is dispensable during the later terminal differentiation stage. Without STAT3, the brown preadipocytes have …

Non-Canonicaly Recruited Tcrαβcd8Αα Iels Recognize Microbial Antigens, Lukasz Wojciech, Edyta Szurek, Michal Kuczma, Anna Cebula, Wessam R. Elhefnawy, Maciej Pietrzak, Grzegorz Rempala, Leszek Ignatowicz

Computer Science Faculty Publications

In the gut, various subsets of intraepithelial T cells (IELs) respond to self or non-self-antigens derived from the body, diet, commensal and pathogenic microbiota. Dominant subset of IELs in the small intestine are TCRαβCD8αα⁺ cells, which are derived from immature thymocytes that express self-reactive TCRs. Although most of TCRαβCD8αα⁺ IELs are thymus-derived, their repertoire adapts to microbial flora. Here, using high throughput TCR sequencing we examined how clonal diversity of TCRαβCD8αα⁺ IELs changes upon exposure to commensal-derived antigens. We found that fraction of CD8αα⁺ IELs and CD4⁺ T cells express identical …

Charecterization Of The Innate Immune Response In The Rat Intervertebral Disc At The Tissue And Cellular Level, Matthew Guerreiro

Theses and Dissertations (Comprehensive)

Low back pain (LBP) affects up to 80% of the global population at some point during their life. The costs associated with LBP are estimated at $100 billion per year, putting significant strains on our healthcare system. As intervertebral disc (IVD) herniation is one of the major causes of LBP we decided to focus on herniation facilitated inflammatory responses, where damage caused by herniation triggers an innate immune response which likely results in pain, inflammation, and recruitment of specialized innate immune cells like macrophages to the affected area. Since the role of the inflammatory response is relatively uncharacterized in the …

Tetratricopeptide 39c (Ttc39c) Is Upregulated During Skeletal Muscle Atrophy And Is Necessary For Muscle Cell Differentiation, Caleb Hayes

UNF Graduate Theses and Dissertations

Ttc39c has been identified as a novel gene in skeletal muscle that is upregulated in response to neurogenic atrophy in mice. Quantitative PCR and Western blot analysis confirmed that Ttc39c is expressed in both proliferating and differentiated muscle cells. Furthermore, comparison of Ttc39c expression in undifferentiated and differentiated C₂C₁₂ cells demonstrated that Ttc39c levels peak in early differentiation, but decreases as cells become fully differentiated myotubes. The transcriptional regulation of Ttc39c was examined by cloning promoter fragments of the gene and fusing it with the SEAP reporter gene. The Ttc39c reporter gene constructs were transfected into muscle …

Evidence For Extra-Gastric Expression Of The Proton Pump H+/K+ -Atpase In The Gills And Kidney Of The Teleost Oreochromis Niloticus, Ebtesam Barnawi

Theses and Dissertations (Comprehensive)

It is well known that stomach acid secretion by oxynticopeptic cells of the gastric mucosa is accomplished by the H⁺/ K⁺-ATPase (HKA), which is comprised of the HKα1 (gene: atp4a) and HKβ (gene: atp4b) subunits. However, the role of the HKA in extra-gastric organs such as the gill and kidney is less clear especially in fishes. This pump may contribute to active ion and/or acid-base regulation either through direct ion transport or through secondary transport proteins against unfavorable concentration gradients via the energy derived from ATP hydrolysis. In the present work I have demonstrated …

A Physical Biology, The Electron Neutrino Mass, And The Role Of Quantum Mechanics In Nature, Maurice Goodman

Articles

In science we need to remove physics and earth science from the fundamental sciences and treat Biology as a fundamental natural (physical) science. Attempts to keep Biology autonomous because it is holistic, from the physical sciences, are just disguised anthropocentrism. Physical sciences have holistic features also. The autonomy of Biology is at odds with a holistic, integrated, science and is preventing progress in science. For example, every cell needs a 'global' communication system to keep order and stability with rapid information transfer across cellular scales. We have yet to figure out how this is achieved. Over the last 30 years, …

The Effect Of The Loss Of Lgl1 In Murine Neural Progenitor Cells On Mapk Signaling And Proliferation, Monique R. Lacourse

Cal Poly Humboldt theses and projects

Glioblastoma is an incurable, aggressive, and highly invasive type of brain tumor that harbors tumor initiating cells characterized by disrupted polarized cell divisions. A cell polarity gene lethal (2) giant larvae 1 (Lgl1) has been implicated in gliomas and is a tumor suppressor initially identified in Drosophila with roles in proliferation. The loss of Lgl1 in Drosophila activates the MAPK protein kinase JNK and the Ras pathway and therefore its downstream kinase ERK, a transcription factor modulator. Furthermore, when Lgl1 is knocked out in mice, a phenotype similar to glioma is seen. Loss of the human form of …

Evaluation Of Extracellular Matrix Composition And Rheology As Determinants Of Growth, Invasion, And Response To Photodynamic Therapy In 3d Cell Culture Models Of Pancreatic Ductal Adenocarcinoma, Gwendolyn M. Cramer

Graduate Doctoral Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is a notoriously lethal disease characterized by prominent stromal involvement, which plays complex roles in regulating tumor growth and therapeutic response. The extracellular matrix (ECM)-rich stroma has been implicated as a barrier to drug penetration, although stromal depletion strategies have had mixed clinical success. It remains less clear how biophysical interactions with the ECM regulate invasive progression and susceptibilities to specific therapies. Here, an integrative approach combining 3D cell culture and quantitative imaging techniques is used to evaluate invasive behavior and motility as determinants of response to classical chemotherapy and photodynamic therapy (PDT), in which light …

Investigating The Role Of Small Noncoding Rnas In Vertebrate Anoxia Tolerance, Claire Louise Riggs

Dissertations and Theses

Very few vertebrates survive extended periods of time without oxygen. Entry into metabolic depression is central to surviving anoxia, which is supported by overall suppression of protein synthesis, yet requires increased expression of specific proteins. Studying the rapid and complex regulation of gene expression associated with survival of anoxia may uncover new mechanisms of cellular biology and transform our understanding of cells, as well as inform prevention and treatment of heart attack and stroke in humans. Small non-coding RNAs (sncRNAs) have emerged as regulators of gene expression that can be rapidly employed, can target individual genes or suites of genes, …

Nuclear Spindles Pave The Way To Metastasis, Patrick J. Hensley, Natasha Kyprianou

Urology Faculty Publications

No abstract provided.

Serine-Dependent Sphingolipid Synthesis Is A Metabolic Liability Of Aneuploid Cells, Sunyoung Hwang, H. Tobias Gustafsson, Ciara O’Sullivan, Gianna Bisceglia, Xinhe Huang, Christian Klose, Andrej Schevchenko, Robert C. Dickson, Paola Cavaliere, Noah Dephoure, Eduardo M. Torres

Molecular and Cellular Biochemistry Faculty Publications

Aneuploidy disrupts cellular homeostasis. However, the molecular mechanisms underlying the physiological responses and adaptation to aneuploidy are not well understood. Deciphering these mechanisms is important because aneuploidy is associated with diseases, including intellectual disability and cancer. Although tumors and mammalian aneuploid cells, including several cancer cell lines, show altered levels of sphingolipids, the role of sphingolipids in aneuploidy remains unknown. Here, we show that ceramides and long-chain bases, sphingolipid molecules that slow proliferation and promote survival, are increased by aneuploidy. Sphingolipid levels are tightly linked to serine synthesis, and inhibiting either serine or sphingolipid synthesis can specifically impair the fitness …

Expression Of Wnt-Signaling Pathway Genes And Their Associations With Mirnas In Colorectal Cancer, Martha L. Slattery, Lila E. Mullany, Lori C. Sakoda, Wade S. Samowitz, Roger K. Wolff, John R. Stevens, Jennifer S. Herrick

Mathematics and Statistics Faculty Publications

The Wnt-signaling pathway functions in regulating cell growth and thus is involved in the carcinogenic process of several cancers, including colorectal cancer. We tested the hypothesis that multiple genes in this signaling pathway are dysregulated and that miRNAs are associated with these dysregulated genes. We used data from 217 colorectal cancer (CRC) cases to evaluate differences in Wnt-signaling pathway gene expression between paired CRC and normal mucosa and identify miRNAs that are associated with these genes. Gene expression data from RNA-Seq and miRNA expression data from Agilent Human miRNA Microarray V19.0 were analyzed. We focused on genes most strongly associated …

Comparative Study Of Spinning Field Development In Two Species Of Araneophagic Spiders (Araneae, Mimetidae, Australomimetus), Mark A. Townley, Danilo Harms

Molecular, Cellular & Biomedical Sciences

External studies of spider spinning fields allow us to make inferences about internal silk gland biology, including what happens to silk glands when the spider molts. Such studies often focus on adults, but juveniles can provide additional insight on spinning apparatus development and character polarity. Here we document and describe spinning fields at all stadia in two species of pirate spider (Mimetidae: Australomimetus spinosus, A. djuka). Pirate spiders nest within the ecribellate orb-building spiders (Araneoidea), but are vagrant, araneophagic members that do not build prey-capture webs. Correspondingly, they lack aggregate and flagelliform silk glands (AG, FL), specialized for forming prey-capture …

Urologist Burnout: Frequency, Causes, And Potential Solutions To An Unspoken Entity, Julie Franc-Guimond, Brian Mcneil, Steven M. Schlossberg, Amanda C. North, Alp Sener

Anatomy and Cell Biology Publications

Physician burnout has been linked to decreased job performance, increased medical errors, interpersonal conflicts, and depression. Recent multispecialty studies suggest that urologists have higher rates (up to 63.6%) of burnout compared to physicians in other specialties; however, these reports were limited by low sample sizes.1 We aimed to evaluate the prevalence of urologist burnout, verify risk factors, and recommend preventative measures and solutions for colleagues at risk or suffering from burnout. Urologist burnout is a true entity that transcends level of training and nationality. Its roots appear to be deep-seated in our tireless efforts to strive for excellence in care …

Potential Anticancer Effect Of Prostratin Through Sik3 Inhibition, Dalal Alotaibi, Suneetha Amara, Terrance L. Johnson, Venkataswarup Tiriveedhi

Biology Faculty Research

Prostratin, a phorbol ester natural plant compound, has been demonstrated to exert an anti‑retroviral effect through activation of latent cluster of differentiation (CD)4+T lymphocytes and inhibition of viral entry into the cell through downregulation of chemokine receptor type 4 (CXCR4) expression. However, the potential effect of prostratin on cancer is yet to be defined. As CXCR4 is well known to induce cancer migration, it was hypothesized that prostratin induces an anti‑cancer effect through inhibition of CXCR4 expression. The authors previously demonstrated that high stimulating conditions (sub‑minimal IL‑17, 0.1 ng/ml, synergized with high salt, Δ0.05 M NaCl) promote breast cancer cell …

Pde8 Is Expressed In Human Airway Smooth Muscle And Selectively Regulates Camp Signaling By Β 2 Ar-Ac6, Timothy B. Johnstone, Kaitlyn H. Smith, Cynthia J. Koziol-White, Fengying Li, Austin G. Kazarian, Maia L. Corpuz, Maya Shumyachter, Frederick J. Ehlert, Bianca E. Himes, Reynold A. Pannettieri Jr., Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Two cAMP signaling compartments centering around adenylyl cyclase (AC) exist in human airway smooth muscle (HASM) cells, one containing ß2AR-AC6 and another containing E prostanoid receptors (EPR)-AC2. We hypothesized that different phosphodiesterase (PDE) isozymes selectively regulate cAMP signaling in each compartment. According to RNA-seq data, 18 of 24 PDE genes were expressed in primary HASM cells derived from age- and gender-matched donors with and without asthma. PDE8A was the third most abundant of the cAMP-degrading PDE genes, after PDE4A and PDE1A. Knockdown of PDE8A using shRNA evoked 2-fold greater cAMP responses to 1 DM forskolin in the presence of IBMX. …

Unseen Science: Modern Discoveries Too Far Away Or Tiny For Human Eyes, Lucy Huang

Capstones

As science has progressed, scientists have realized that evidence goes beyond the realms of physical sight. Whether it is too small or difficult to find, scientists have developed different ways to get around this problem. We see this in cancer genomics and in extrasolar planetary research. Scientists use what they know and what they measure to validate their work.

https://lucy-huang-9tge.squarespace.com/

Mitochondrial Dynamics And Respiration Within Cells With Increased Open Pore Cytoskeletal Meshes, David H. Jang, Sarah C. Seeger, Martha E. Grady, Frances S. Shofer, David M. Eckmann

Mechanical Engineering Faculty Publications

The cytoskeletal architecture directly affects the morphology, motility, and tensional homeostasis of the cell. In addition, the cytoskeleton is important for mitosis, intracellular traffic, organelle motility, and even cellular respiration. The organelle responsible for a majority of the energy conversion for the cell, the mitochondrion, has a dependence on the cytoskeleton for mobility and function. In previous studies, we established that cytoskeletal inhibitors altered the movement of the mitochondria, their morphology, and their respiration in human dermal fibroblasts. Here, we use this protocol to investigate applicability of power law diffusion to describe mitochondrial locomotion, assessment of rates of fission and …

Metabolic Dysregulation And Cancer Mortality In A National Cohort Of Blacks And Whites, Tomi Akinyemiju, Justin Xavier Moore, Suzanne Judd, Susan Lakoski, Michael Goodman, Monika M. Safford, Maria Pisu

Epidemiology and Environmental Health Faculty Publications

Background: We examined the association between metabolic dysregulation and cancer mortality in a prospective cohort of Black and White adults.

Methods: A total of 25,038 Black and White adults were included in the analysis. Metabolic dysregulation was defined in two ways: 1) using the joint harmonized criteria for metabolic syndrome (MetS) and 2) based on factor analysis of 15 variables characterizing metabolic dysregulation. We estimated hazards ratios (HRs) and 95% confidence intervals (CIs) for the association of MetS and metabolic dysregulation with cancer mortality during follow-up using Cox proportional hazards models.

Results: About 46% of Black and 39% of White …

9-Aminoacridine Inhibits Ribosome Biogenesis And Synergizes With Cytotoxic Drugs To Induce Selective Killing Of P53-Deficient Cells, Leonid Anikin, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Common cancer treatments target rapidly dividing cells and do not discriminate between cancer and normal host cells. One approach to mitigating negative side‐effects of cancer treatment is to temporarily arrest cell cycle progression and thus protect normal cells during cytotoxic treatments, a concept called cyclotherapy. We recently proposed that transient inhibition of post‐transcriptional steps of ribosome biogenesis (RBG) can be used to selectively arrest p53‐positive host cells and not p53‐null cancer cells. In this study, we investigated whether cytoprotective RBG inhibition can be achieved through small molecule treatment.

Modification Of The Ribosome As Part Of The Adaptive Response To Oxidative Stress In Yeast, Jessica A Zinskie, Daniel Shedlovskiy, Ethan Gardner, Dimitri G Pestov, Natalia Shcherbik

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Living organisms are constantly exposed to a variety of environmental and internal stressors tha tare detrimental to their cellular physiology and viability. One such condition, oxidativestress, is caused by abnormal amounts of Reactive Oxygen Species (ROS) that can lead to damage to proteins, nucleic acids, and lipids. Although the mechanisms to neutralize ROS have been widely studied, the understanding of ROS‐mediated signaling for these mechanisms is rather incomplete and sparse. We have uncovered a previously undescribed phenomenon of yeast ribosomes to respond to elevated levels of ROS through a specific endonucleolytic cleavage of the 25S rRNA in the c‐loop of …

Targeting Ribosome Assembly Factors Selectively Protects P53 Positive Cells From Chemotherapeutic Agents, Russell T. Sapio, Anastasiya Nezdyur, Matthew Krevetski, Leonid Anikin, Vincent J. Manna, N. Minkovsky, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Many chemotherapeutic agents act in a nondiscriminatory fashion, targeting both cancerous and noncancerous cells in Sphase and Mphase. One approach to reduce the toxic side effects in normal tissue is to exploit the differences in p53 functionality between cancerous and noncancerous cells. For example, activating p53 signaling by nongenotoxic means can transiently arrest noncancerous p53 positive cells in G1 phase and protect them from the cytotoxic effects of chemotherapeutic drugs. However, since most cancerous cells have faulty p53 signaling, they will proceed to cycle, and continue to be affected by the drug. In this study we asked if this G1‐phase …

The Role Of Mapk And Scf In The Destruction Of Med13 In Cyclin C Mediated Cell Death, David C Stieg, Stephen D Willis, Joseph Scuorzo, Mia Song, Vidyaramanan Ganesan, Randy Strich, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

In response to stress, the yeast¹ and mammalian² cyclin C translocate from the nucleus to the cytoplasm, where it associates with the GTPase Drp1/Dnm1 to drive mitochondrial fragmentation and apoptosis. Therefore, the decision to release cyclin C represents a key life or death decision. In unstressed cells, the cyclin C‐Cdk8 kinase regulates transcription by associating with the Mediator of RNA polymerase II. We previously reported that the Mediator component Med13 anchors cyclin C in the nucleus³. Loss of Med13 function leads to constitutive cytoplasmic localization of cyclin C, resulting in fragmented mitochondria, hypersensitivity to stress and …

Snf1 Dependent Destruction Of Med13 Is Required For Programmed Cell Death Following Oxidative Stress In Yeast, Stephen D Willis, David C Stieg, R. Shah, Randy Strich, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

All eukaryotic cells, when faced with unfavorable environmental conditions, have to decide whether to mount a survival or cell death response. The conserved cyclin C and its kinase partner Cdk8 play a key role in this decision. Both are members of the Cdk8 kinase module that, along with Med12 and Med13, associate with the core mediator complex of RNA polymerase II. In S. cerevisiae, oxidative stress triggers Med13 destruction¹, which thereafter releases cyclin Ci nto the cytoplasm. Cytoplasmic cyclin C associates with mitochondria where it induces hyper-fragmentation and programmed cell death². This suggests a model in …

Translocation Of Cyclin C During Oxidative Stress Is Regulated By Interactions With Multiple Trafficking Proteins, Daniel G J Smethurst, Katrina F Cooper, Randy Strich

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Eukaryotic cells take cues from their environment and interpret them to enact a response. External stresses can produce a decision between adjusting to behaviors which promote surviving the stress, or enacting a cell death program. The decision to undergo programmed cell death (PCD) is controlled by a complex interaction between nuclear and mitochondrial signals. The mitochondria are highly dynamic organelles that constantly undergo fission and fusion. However, a dramatic shift in mitochondrial morphology toward fission occurs early in the PCD process. We have identified the transcription factor cyclin C as the biochemical trigger for stress‐induced mitochondrial hyper‐fragmentation in yeast (Cooper …

Mechanistic Insights Into The Regulation Of Mitochondrial Fission By Cyclin C, Vidyaramanan Ganesan, Katrina F Cooper, Randy Strich

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Cyclin C is a component of the mediator complex of RNA polymerase II that localizes to the nucleus under normal conditions. In response to stress, cyclin C translocates to the cytosol and mitochondria and mediates stress‐induced mitochondrial fission and apoptosis. The molecular mechanisms by which cyclin C induces mitochondrial fission are unknown. Using in vitro experimental approaches, we sought to investigate the mechanistic basis of cyclin C mediated mitochondrial fission.

Type 2 Neural Progenitor Cell Activation Drives Reactive Neurogenesis After Binge-Like Alcohol Exposure In Adolescent Male Rats, Chelsea Rhea Geil Nickell, Hui Peng, Dayna M. Hayes, Kevin Y. Chen, Justin A. Mcclain, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

Excessive alcohol consumption during adolescence remains a significant health concern as alcohol drinking during adolescence increases the likelihood of an alcohol use disorder in adulthood by fourfold. Binge drinking in adolescence is a particular problem as binge-pattern consumption is the biggest predictor of neurodegeneration from alcohol and adolescents are particularly susceptible to the damaging effects of alcohol. The adolescent hippocampus, in particular, is highly susceptible to alcohol-induced structural and functional effects, including volume and neuron loss. However, hippocampal structure and function may recover with abstinence and, like in adults, a reactive burst in hippocampal neurogenesis in abstinence may contribute to …