Cell and Developmental Biology Commons^™

Differential Expression Of Αvβ3 And Αvβ6 Integrins In Prostate Cancer Progression, Fabio Quaglia, Shiv Ram Krishn, Yanqing Wang, David W Goodrich, Peter Mccue, Andrew Kossenkov, Amy C Mandigo, Karen Knudsen, Paul H Weinreb, Eva Corey, William Kevin Kelly, Lucia R Languino

Department of Cancer Biology Faculty Papers

Neuroendocrine prostate cancer (NEPrCa) arises de novo or after accumulation of genomic alterations in pre-existing adenocarcinoma tumors in response to androgen deprivation therapies. We have provided evidence that small extracellular vesicles released by PrCa cells and containing the αVβ3 integrin promote neuroendocrine differentiation of PrCa in vivo and in vitro. Here, we examined αVβ3 integrin expression in three murine models carrying a deletion of PTEN (SKO), PTEN and RB1 (DKO), or PTEN, RB1 and TRP53 (TKO) genes in the prostatic epithelium; of these three models, the DKO and TKO tumors develop NEPrCa with a gene signature comparable to those of …

Inhibition Of Biofilm Formation By The Synergistic Action Of Egcg-S And Antibiotics, Shrameeta Shinde, Lee Lee, Tinchun Chu

Department of Biology Faculty Scholarship and Creative Works

Biofilm, a stress-induced physiological state, is an established means of antimicrobial tolerance. A perpetual increase in multidrug resistant (MDR) infections associated with high mortality and morbidity have been observed in healthcare settings. Multiple studies have indicated that the use of natural products can prevent bacterial growth. Recent studies in the field have identified that epigallocatechin gallate (EGCG), a green tea polyphenol, could disrupt bacterial biofilms. A modified lipid-soluble EGCG, epigallocatechin-3-gallate-stearate (EGCG-S), has enhanced the beneficial properties of green tea. This study focuses on utilizing EGCG-S as a novel synergistic agent with antibiotics to prevent or control biofilm. Different formulations of …

Topsentinol L Trisulfate, A Marine Natural Product That Targets Basal-Like And Claudin-Low Breast Cancers, Nader N. El-Chaar, Thomas E. Smith, Gajendra Shrestha, Stephen R. Piccolo, Mary Kay Harper, Ryan M. Van Wagoner, Zhenyu Lu, Ashlee R. Venancio, Chris M. Ireland, Andrea H. Bild, Philip J. Moos

Faculty Publications

Patients diagnosed with basal-like breast cancer suffer from poor prognosis and limited treatment options. There is an urgent need to identify new targets that can benefit patients with basal-like and claudin-low (BL-CL) breast cancers. We screened fractions from our Marine Invertebrate Compound Library (MICL) to identify compounds that specifically target BL-CL breast cancers. We identified a previously unreported trisulfated sterol, i.e., topsentinol L trisulfate (TLT), which exhibited increased efficacy against BL-CL breast cancers relative to luminal/HER2+ breast cancer. Biochemical investigation of the effects of TLT on BL-CL cell lines revealed its ability to inhibit activation of AMP-activated protein kinase (AMPK) …

[(Wr)8Wkβa]-Doxorubicin Conjugate: A Delivery System To Overcome Multi-Drug Resistance Against Doxorubicin, Khalid Zoghebi, Hamidreza Montazeri Aliabadi, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin (Dox) is an anthracycline chemotherapeutic agent used to treat breast, leukemia, and lymphoma malignancies. However, cardiotoxicity and inherent acquired resistance are major drawbacks, limiting its clinical application. We have previously shown that cyclic peptide [WR]₉ containing alternate tryptophan (W) and arginine (R) residues acts as an efficient molecular transporter. An amphiphilic cyclic peptide containing a lysine (K) residue and alternative W and R was conjugated through a free side chain amino group with Dox via a glutarate linker to afford [(WR)₈WKβA]-Dox conjugate. Antiproliferative assays were performed in different cancer cell lines using the conjugate and the …

The Circadian Cryptochrome, Cry1, Is A Pro-Tumorigenic Factor That Rhythmically Modulates Dna Repair., Ayesha A Shafi, Chris M Mcnair, Jennifer J Mccann, Mohammed Alshalalfa, Anton Shostak, Tesa M Severson, Yanyun Zhu, Andre Bergman, Nicolas Gordon, Amy C Mandigo, Saswati N Chand, Peter Gallagher, Emanuela Dylgjeri, Talya S Laufer, Irina A Vasilevskaya, Matthew J Schiewer, Michael Brunner, Felix Y Feng, Wilbert Zwart, Karen E Knudsen

Department of Cancer Biology Faculty Papers

Mechanisms regulating DNA repair processes remain incompletely defined. Here, the circadian factor CRY1, an evolutionally conserved transcriptional coregulator, is identified as a tumor specific regulator of DNA repair. Key findings demonstrate that CRY1 expression is androgen-responsive and associates with poor outcome in prostate cancer. Functional studies and first-in-field mapping of the CRY1 cistrome and transcriptome reveal that CRY1 regulates DNA repair and the G2/M transition. DNA damage stabilizes CRY1 in cancer (in vitro, in vivo, and human tumors ex vivo), which proves critical for efficient DNA repair. Further mechanistic investigation shows that stabilized CRY1 temporally regulates expression of genes required …

Oligodendroglial Epigenetics, From Lineage Specification To Activity-Dependent Myelination, Mathilde Mathilde Pruvost, Sarah Moyon

Advanced Science Research Center

Oligodendroglial cells are the myelinating cells of the central nervous system. While myelination is crucial to axonal activity and conduction, oligodendrocyte progenitor cells and oligodendrocytes have also been shown to be essential for neuronal support and metabolism. Thus, a tight regulation of oligodendroglial cell specification, proliferation, and myelination is required for correct neuronal connectivity and function. Here, we review the role of epigenetic modifications in oligodendroglial lineage cells. First, we briefly describe the epigenetic modalities of gene regulation, which are known to have a role in oligodendroglial cells. We then address how epigenetic enzymes and/or marks have been associated with …

Differentiating Human Embryonic Stem Cells In Micropatterns To Study Cell Fate Specification And Morphogenetic Events During Gastrulation, Kyaw Thu Minn

McKelvey School of Engineering Graduate Student Theses & Dissertations

During mammalian embryogenesis, the first major lineage segregation occurs when embryonic epiblast, and extraembryonic trophectoderm and hypoblast arise in the blastocyst. In the next fundamental and conserved phase of animal embryogenesis known as gastrulation, extraembryonic cells provide signals to epiblast to instruct embryonic patterning, and epiblast gives rise to germ layers ectoderm, mesoderm, and endoderm, that will establish all embryonic tissues. Proper specification and morphogenesis of germ layers during gastrulation is vital for correct embryonic development. Due to ethical and legal restrictions limiting human embryo studies, human gastrulation is poorly understood. Our knowledge of human gastrulation has largely been derived …

In Vivo Optical Metabolic Imaging Of Long-Chain Fatty Acid Uptake In Orthotopic Models Of Triple-Negative Breast Cancer, Megan C. Madonna, Joy E. Duer, Joyce V. Lee, Jeremy Williams, Baris Avsaroglu, Caigang Zhu, Riley Deutsch, Roujia Wang, Brian T. Crouch, Matthew D. Hirschey, Andrei Goga, Nirmala Ramanujam

Biomedical Engineering Faculty Publications

Targeting a tumor’s metabolic dependencies is a clinically actionable therapeutic approach; however, identifying subtypes of tumors likely to respond remains difficult. The use of lipids as a nutrient source is of particular importance, especially in breast cancer. Imaging techniques offer the opportunity to quantify nutrient use in preclinical tumor models to guide development of new drugs that restrict uptake or utilization of these nutrients. We describe a fast and dynamic approach to image fatty acid uptake in vivo and demonstrate its relevance to study both tumor metabolic reprogramming directly, as well as the effectiveness of drugs targeting lipid metabolism. Specifically, …

Cyclin-Dependent Kinase 1 And Aurora Kinase Choreograph Mitotic Storage And Redistribution Of A Growth Factor Receptor, C. D. Cota, M. S. Dreier , '20, W. Colgan, A. Cha, Twan Sia , '21, Bradley Justin Davidson , '91

Biology Faculty Works

Endosomal trafficking of receptors and associated proteins plays a critical role in signal processing. Until recently, it was thought that trafficking was shut down during cell division. Thus, remarkably, the regulation of trafficking during division remains poorly characterized. Here we delineate the role of mitotic kinases in receptor trafficking during asymmetric division. Targeted perturbations reveal that Cyclin-dependent Kinase 1 (CDK1) and Aurora Kinase promote storage of Fibroblast Growth Factor Receptors (FGFRs) by suppressing endosomal degradation and recycling pathways. As cells progress through metaphase, loss of CDK1 activity permits differential degradation and targeted recycling of stored receptors, leading to asymmetric induction. …

Na/K-Atpase Alphα1 Regulates Adipogenesis Via Its Conserved Caveolin Binding Motif, Minqi Huang

Theses, Dissertations and Capstones

The Na/K-ATPase (NKA) was identified in 1957 by Dr. Jens C. Skou. It belongs to the P-type ATPase family, which can actively transport ions across cell membranes by using the energy from adenosine triphosphate (ATP) hydrolysis. During the second half of the 20th century, the molecular mechanism of the NKA catalytic cycle was clarified, and the isoform diversity of NKA in different species and organs was identified. The active ion transport through NKA generates cell membrane ion gradients and the electric potential. Hence, the enzymatic function of NKA is critical for cell viability as well as multiple physiological processes including …

Potential Counter Regulatory Effects Of A Gut Microbiota Metabolite In Alleviating Down-Regulation Krüppel-Like Factor 4 In Intestinal Inflammation, Ylva Forslund

Theses, Dissertations and Capstones

Inflammatory bowel disease (IBD) is a medical condition characterized by chronic inflammation of the intestinal epithelium. Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, is vital for maintaining intestinal epithelial homeostasis. KLF4 promotes differentiation of goblet cells that generate the protective mucus layer. Reduced goblet cell number and defective mucus layer are associated with IBD. Shortchain fatty acids (SCFA) are known to play an important role in the maintenance of a strong and healthy intestinal epithelial layer and also in goblet cell differentiation. However, whether the positive effects of SCFAs on goblet cells are mediated, at least partly, via …

High Prevalence Of Pre-Existing Serological Cross-Reactivity Against Severe Acute Respiratory Syndrome Coronavirus-2 (Sars-Cov-2) In Sub-Saharan Africa, For Yue Tso, Salum J. Lidenge, Phoebe B. Peña, Ashley A. Clegg, John R. Ngowi, Julius Mwaiselage, Owen Ngalamika, Peter Julius, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Objective: Significant morbidity and mortality have occurred in the USA, Europe, and Asia due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whereas the numbers of infections and deaths in sub-Saharan Africa (SSA) have remained comparatively low. It has been hypothesized that exposure of the population in SSA to other coronaviruses prior to the COVID-19 pandemic resulted in some degree of cross-protection against SARS-CoV-2 infection and pathogenesis. We evaluated this hypothesis by comparing SARS-CoV-2 cross-reactive antibodies in pre-pandemic plasma samples collected from SSA and the USA.

Method: Pre-COVID-19 pandemic plasma samples from SSA and the USA were collected and tested by …

Development Of Endoplasmic Reticulum Targeted Probes And Red Fluorescent Probes For Detecting Zinc, Drew Maslar

Electronic Theses and Dissertations

Zinc (Zn²⁺) is the second most abundant transition metal in the body and is important in various biological functions. Fluorescent sensors based on circularly permuted fluorescent proteins (cpFPs) have been previously made to detect labile, or unbound, Zn²⁺ within the cytoplasm of cells. These sensors have proven invaluable for studying Zn²⁺, however, these sensors are limited to their use in the cytoplasm and by the fact that only green cpFP have been utilized to create fluorescent Zn²⁺ sensors. In this thesis, we use a combination of peptide targeting sequences, site-directed mutagenesis, and rational design …

Characterization Of The Whale Shark (Rhincodon Typus) Melanocortin-2 Receptor, Brianne Hoglin

Electronic Theses and Dissertations

Among bony vertebrates, the melanocortin-2 receptor ortholog is unique among the family of five melanocortin receptors on the basis that it is dependent on its accessory protein, MRAP1, for trafficking and activation, and is selective for activation by ACTH alone. Previous studies on the MC2R orthologs of select cartilaginous fish, the elephant shark (Callorhinchus milii) and the red stingray (Dasyatis akajei), revealed divergent traits in a less obligatory relationship on MRAP1 and its ability to be activated by ACTH or the MSH-sized peptides. However, observed traits were not consistent between these two cartilaginous fish species, posing …

Targeting Epigenetic Mechanisms In Endometriosis, Sarah Elizabeth Brunty

Theses, Dissertations and Capstones

Endometriosis is a complex and elusive gynecological disease in which the inner lining of the uterus grows in locations outside of the uterus and forms lesions. It is known to affect 1 in 9 women of reproductive age worldwide. Symptoms of endometriosis include severe pain, heavy periods, and infertility. While multiple theories of origin exist, none fully encompass all aspects of the disease, although all theories agree that this is an inflammation-driven disease. Due to this, many researchers are turning towards epigenetics to explain the initiation and progression of endometriosis. However, what is causing these epigenetic changes is still a …

Viropana (Vna) 5, Abijeet Singh Mehta, Panagiotis A. Tsonis, Amit Singh

Components of a Regeneration Toolkit: Notophthalmus viridescens

Viropana (vna) 5

• ID – vna 5
• Details – Gene from a novel protein family belonging to the regeneration toolkit of Notophthalmus viridescens
• Base pairs – 391

Viropana (Vna) 1, Abijeet Singh Mehta, Panagiotis A. Tsonis, Amit Singh

Components of a Regeneration Toolkit: Notophthalmus viridescens

Viropana (vna) 1

• ID – vna 1

• Details – Gene from a novel protein family belonging to the regeneration toolkit of Notophthalmus viridescens

• Base pairs – 492

Propranolol Sensitizes Vascular Sarcoma Cells To Doxorubicin By Altering Lysosomal Drug Sequestration And Drug Efflux, Jhuma Saha, Jong Hyuk Kim, Clarissa N. Amaya, Caleb M. Witcher, Ali Khammanivong, Derek M. Korpela, David R. Brown, Josephine Taylor, Brad A. Bryan, Erin B. Dickerson

Faculty Publications

Angiosarcoma is a rare cancer of blood vessel–forming cells with a high patient mortality and few treatment options. Although chemotherapy often produces initial clinical responses, outcomes remain poor, largely due to the development of drug resistance. We previously identified a subset of doxorubicin-resistant cells in human angiosarcoma and canine hemangiosarcoma cell lines that exhibit high lysosomal accumulation of doxorubicin. Hydrophobic, weak base chemotherapeutics, like doxorubicin, are known to sequester within lysosomes, promoting resistance by limiting drug accessibility to cellular targets. Drug synergy between the beta adrenergic receptor (β-AR) antagonist, propranolol, and multiple chemotherapeutics has been documented in vitro, and …

The Effects Of Rolipram, A Selective Phosphodiesterase Inhibitor, On Immortalized Schwann Cell Proliferation, Akap95 And Cyclin D3 Expression, Kyle P. Kenney, Mary Pistack, Angela Asirvatham

Student Research Poster Presentations 2021

Schwann cells are a vital component of the Peripheral Nervous System and aid in the repair of axons following injury. The regulation of Schwann cell growth in vitro is facilitated by heregulin, a neuron-secreted growth factor, and an unknown mitogen that activates the cyclic adenosine monophosphate (cAMP) pathway. The abundance of intracellular cAMP is regulated by a family of enzymes called phosphodiesterases (PDEs). PDE inhibitors such as rolipram have therapeutic potential in various disorders and function by increasing the levels of intracellular cAMP. A-Kinase anchoring proteins (AKAPs), a family of scaffolding proteins that belong to the cAMP/Protein Kinase A (PKA) …

Characterizing Ferroptosis Pathways In In Vitro Motor Neuron Models, Alejandra Martinez

Theses and Dissertations

Ferroptosis is a non-apoptotic regulated form of cell death driven by the toxic accumulation of lipid peroxides and the presence of iron. The mechanism by which ferroptosis operates requires further investigation; here I will discuss the findings regarding the role of ferroptosis in different cellular models as well as the genes that may be involved with either promoting or hindering the ferroptotic pathway. NSC-34 is a hybrid cell line of neuroblastoma and primary spinal cord cells that can be differentiated into a motor neuron-like state allowing the characterization of ferroptosis in two distinct cellular conditions. Additionally, iNIL cells are a …