Cell Biology Commons^™

P23. Elucidation Of The Signaling Pathway Of Mertk, Kyle Taruc

Western Research Forum

Background

Mer Tyrosine Kinase (MERTK) is a receptor which mediates efferocytosis – removal of apoptotic cells by phagocytes such as macrophages. MERTK plays a critical role in homeostasis, with mutations in MERTK associated with the development and progression of atherosclerosis, the buildup of cholesterol-laden plaque in the sub-arterial space. Indeed, one MERTK allele is associated with 66% (heterozygous) to 75% (homozygous) protection from atherosclerosis, while other alleles and SNP’s pre-dispose to atherosclerosis and autoimmunity. Complications resulting from atherosclerosis, including heart attack and stroke, are currently the second leading cause of mortality in Canada. Despite the importance of MERTK in atherosclerosis …

P32. Altered Sensory Processing In Response To Novel Dreadd-Induced Inactivation Of Gaba In Pedunculopontine Tegmental Nucleus, Niveen Fulcher

Western Research Forum

Niveen Fulcher¹, Cleusa De Oliveira², & Susanne Schmid^1,2

¹Schulich School of Medicine & Dentistry, University of Western Ontario

²Anatomy and Cell Biology, University of Western Ontario

Altered sensory processing in response to novel DREADD-induced inactivation of GABA in pedunculopontine tegmental nucleus

Background: Sensory processing deficits are associated with certain psychiatric illnesses, such as schizophrenia and autism spectrum disorder (ASD). Sensory filtering and sensorimotor gating are evolutionarily conserved preattentive responses that filter and block redundant sensory stimuli that would otherwise overwhelm our brains. To date, underlying mechanisms of these deficits are undefined. Prepulse …

Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer

Western Research Forum

Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the …

Relb Expression Determines The Differential Effects Of Ascorbic Acid In Normal And Cancer Cells, Xiaowei Wei, Yong Xu, Fang Fang Xu, Luksana Chaiswing, David M. Schnell, Teresa Noel, Chi Wang, Jinfei Chen, Daret K. St. Clair, William H. St. Clair

Toxicology and Cancer Biology Faculty Publications

Cancer cells typically experience higher oxidative stress than normal cells, such that elevating pro-oxidant levels can trigger cancer cell death. Although pre-exposure to mild oxidative agents will sensitize cancer cells to radiation, this pre-exposure may also activate the adaptive stress defense system in normal cells. Ascorbic acid is a prototype redox modulator that when infused intravenously appears to kill cancers without injury to normal tissues; however, the mechanisms involved remain elusive. In this study, we show how ascorbic acid kills cancer cells and sensitizes prostate cancer to radiation therapy while also conferring protection upon normal prostate epithelial cells against radiation-induced …

Small Grants Make A Big Difference, Susan Walsh

Faculty Publications

No abstract provided.

Dub3 Inhibition Suppresses Breast Cancer Invasion And Metastasis By Promoting Snail1 Degradation, Yadi Wu, Yu Wang, Yiwei Lin, Yajuan Liu, Yifan Wang, Jianhang Jia, Puja Singh, Young-In Chi, Chi Wang, Chenfang Dong, Wei Li, Min Tao, Dana L. Napier, Qiuying Shi, Jiong Deng, B. Mark Evers, Binhua P. Zhou

Pharmacology and Nutritional Sciences Faculty Publications

Snail1, a key transcription factor of epithelial–mesenchymal transition (EMT), is subjected to ubiquitination and degradation, but the mechanism by which Snail1 is stabilized in tumours remains unclear. We identify Dub3 as a bona fide Snail1 deubiquitinase, which interacts with and stabilizes Snail1. Dub3 is overexpressed in breast cancer; knockdown of Dub3 resulted in Snail1 destabilization, suppressed EMT and decreased tumour cell migration, invasion, and metastasis. These effects are rescued by ectopic Snail1 expression. IL-6 also stabilizes Snail1 by inducing Dub3 expression, the specific inhibitor WP1130 binds to Dub3 and inhibits the Dub3-mediating Snail1 stabilization in vitroand in vivo. …

Sumo Regulates The Activity Of Smoothened And Costal-2 In Drosophila Hedgehog Signaling, Jie Zhang, Yajuan Liu, Kai Jiang, Jianhang Jia

Markey Cancer Center Faculty Publications

In Hedgehog (Hh) signaling, the GPCR-family protein Smoothened (Smo) acts as a signal transducer that is regulated by phosphorylation and ubiquitination, which ultimately change the cell surface accumulation of Smo. However, it is not clear whether Smo is regulated by other post-translational modifications, such as sumoylation. Here, we demonstrate that knockdown of the small ubiquitin-related modifier (SUMO) pathway components Ubc9 (a SUMO-conjugating enzyme E2), PIAS (a SUMO-protein ligase E3), and Smt3 (the SUMO isoform in Drosophila) by RNAi prevents Smo accumulation and alters Smo activity in the wing. We further show that Hh-induced-sumoylation stabilizes Smo, whereas desumoylation by Ulp1 …

Effects Of Al3+ And La3+ Trivalent Metal Ions On Tomato Fruit Proteomes, Sasikiran Sangireddy, Ikenna Okekeogbu, Zhujia Ye, Suping Zhou, Kevin J. Howe, Tara Fish, Theodore W. Thannhauser

Agricultural and Environmental Sciences Faculty Research

The tomato (Solanum lycopersicum) ripening process from mature green (MG) to turning and then to red stages is accompanied by the occurrences of physiological and biochemical reactions, which ultimately result in the formation of the flavor, color and texture of ripe fruits. The two trivalent metal ions Al³⁺ and La³⁺ are known to induce different levels of phytotoxicity in suppressing root growth. This paper aims to understand the impacts of these two metal ions on tomato fruit proteomes. Tomato ‘Micro-Tom’ plants were grown in a hydroponic culture system supplemented with 50 μM aluminum sulfate (Al₂ (SO4)_{3 …}

Osteoblast-Derived Fgf9 Regulates Skeletal Homeostasis, Liping Wang, Theresa M. Roth, Marcia J. Abbott, Linh Ho, Lalita Wattanachanya, Robert A. Nissenson

Health Sciences and Kinesiology Faculty Articles

FGF9 has complex and important roles in skeletal development and repair. We have previously observed that Fgf9 expression in osteoblasts (OBs) is regulated by G protein signaling and therefore the present study was done to determine whether OB-derived FGF9 was important in skeletal homeostasis. To directly test this idea, we deleted functional expression of Fgf9 gene in OBs using a 2.3 kb collagen type I promoter-driven Cre transgenic mouse line (Fgf9^{OB −/−}). Both Fgf9 knockout (Fgf9^{OB −/−}) and the Fgf9 floxed littermates (Fgf9^fl/fl) mice were fully backcrossed and maintained in an FBV/N background. Three …

Differentiation And Containment Of Derived Pancreatic Beta Cells, Caden Duffy, Alonzo Cook Ph.D.

Biomedical Engineering Western Regional Conference

Currently, the only permanent cure for Type 1 Diabetes is a pancreatic or islet transplant. With the shortage of donors, we are progressing research towards alternative therapies by differentiating induced pluripotent stem cells into derived pancreatic β-cells that can be transplanted and used as treatment for Type 1 Diabetes. We are investigating methods to increase the yield of fully derived, insulin producing pancreatic β-cells and are additionally researching the use of hydrophilized expanded polytetrafluoroethylene for use in cell containment devices. These devices could offer a future alternative for islet transplantation in human patients.

The Molecular Basis Of Talin2'S High Affinity Toward Β1-Integrin, Yaxia Yuan, Liqing Li, Yanyan Zhu, Lei Qi, Latifeh Azizi, Vesa P. Hytönen, Chang-Guo Zhan, Cai Huang

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Talin interacts with β-integrin tails and actin to control integrin activation, thus regulating focal adhesion dynamics and cell migration. There are two talin genes, Tln1 and Tln2, which encode talin1 and talin2, and it is generally believed that talin2 functions redundantly with talin1. However, we show here that talin2 has a higher affinity to β1-integrin tails than talin1. Mutation of talin2 S339 to leucine, which can cause Fifth Finger Camptodactyly, a human genetic disease, completely disrupted its binding to β–integrin tails. Also, substitution of talin1 C336 with Ser enhanced the affinity of talin1, whereas substitution of talin2 S339 with …

Yeast Help Identify Cytopathic Factors Of Zika Virus, Michael I. Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Accumulating evidence implicates Zika virus (ZIKV) in pathogenesis of microcephaly in newborns and Guillain-Barré syndrome in adults. However, it remains unclear which viral proteins are responsible for these effects and what are the underlying mechanisms of their pathogenic activity. A recent paper by Drs. Zhao and Gallo, and their colleagues at University of Maryland in Baltimore used fission yeast for genome-wide analysis of ZIKV proteins. They demonstrated cytopathogenic activity for seven ZIKV proteins, anaC, C, prM, M, E, NS2B and NS4A. This activity was shown to be dependent on oxidative stress, and for NS4A they demonstrated involvement of the TOR …

Biophysical Tools To Study Cellular Mechanotransduction, Ismeel Muhamed, Farhan Chowdhury, Venkat Maruthamuthu

Mechanical & Aerospace Engineering Faculty Publications

The cell membrane is the interface that volumetrically isolates cellular components from the cell's environment. Proteins embedded within and on the membrane have varied biological functions: reception of external biochemical signals, as membrane channels, amplification and regulation of chemical signals through secondary messenger molecules, controlled exocytosis, endocytosis, phagocytosis, organized recruitment and sequestration of cytosolic complex proteins, cell division processes, organization of the cytoskeleton and more. The membrane's bioelectrical role is enabled by the physiologically controlled release and accumulation of electrochemical potential modulating molecules across the membrane through specialized ion channels (e.g., Na^⁺, Ca²⁺, K^⁺ channels). …

Environmental Changes Turn On The Sinorhizobium Melitloti Exor-Exos/Chvi (Rsi) Host Invasion Switch, Shari N. Walcott

Dissertations, Theses, and Capstone Projects

The free-living Gram-negative soil bacterium, Sinorhizobium meliloti, must switch into its host-invading form in order to infect the root hairs of the host plant, alfalfa (Medicago sativa), and establish a nitrogen-fixing symbiosis. The activation of the switch is believed to occur inside the infection chamber that is formed by curling of the root hairs. It is not fully understood what signals in the environment of the root hairs trigger and infection chamber S. meliloti to switch into a host-invading form since these signals were not extensively examined until now. This switch can be observed directly, due to …

Adaptor Protein 2 (Ap-2) Complex Is Essential For Functional Axogenesis In Hippocampal Neurons, Jae Won Kyung, In Ha Cho, Sukmook Lee, Woo Keun Song, Timothy A. Ryan, Michael B. Hoppa, Sung Hyun Kim

Dartmouth Scholarship

The complexity and diversity of a neural network requires regulated elongation and branching of axons, as well as the formation of synapses between neurons. In the present study we explore the role of AP-2, a key endocytic adaptor protein complex, in the development of rat hippocampal neurons. We found that the loss of AP-2 during the early stage of development resulted in impaired axon extension and failed maturation of the axon initial segment (AIS). Normally the AIS performs two tasks in

concert, stabilizing neural polarity and generating action potentials. In AP-2 silenced axons polarity is established, however there is a …

Mechanisms Of Ikbke Activation In Cancer, Sridevi Challa

USF Tampa Graduate Theses and Dissertations

Cancer is the second leading cause of death in the USA and it is expected to surpass heart diseases making it important to understand the underlying mechanisms of cancer. The efforts to target single signaling molecule showed little success in increasing the patient survival and it can be due to increased compensation for cell survival by alternative pathway activations. Hence comprehensive understanding of the alternative signaling pathways may help us treat cancer better. Chronic inflammation is attributed to increased risk of cancer and emerging studies show the growing importance of both canonical and non-canonical IκB kinases such as IKKα, IKKβ, …

Bioethics In The Work Of Ernest Everett Just: + Missing - Some 400 Pages, Theodore Walker

Perkins Faculty Research and Special Events

Biology + ethics = bioethics. Here we see that Howard University biologist Ernest Everett Just (born 1883, died 1941) connected biology to ethics.

According to Just, various forms of specific biology (including especially cell biology) plus “general biology” are necessary for explaining adequately the origin of ethical behaviors. Social ethical behaviors, especially mutual aid and cooperative interactions with others and the environment, are essential to evolutionary advances among living creatures, ranging from humans to cells. Accordingly, theory of ethics (moral theory) should have roots in biology.

Also, Just wrote an unpublished book-length manuscript—“some 400 typed pages” (Just 1940)—on seeking the …

Evolutionary Adaptations Of Biofilms Infecting Cystic Fibrosis Lungs Promote Mechanical Toughness By Adjusting Polysaccharide Production, Kristin Kovach, Megan Davis-Fields, Yasuhiko Irie, Kanishk Jain, Shashvat Doorwar, Katherine Vuong, Numa Dhamani, Kishore Mohanty, Ahmed Touhami, Vernita D. Gordon

Biology Faculty Publications

Biofilms are communities of microbes embedded in a matrix of extracellular polymeric substances, largely polysaccharides. Multiple types of extracellular polymeric substances can be produced by a single bacterial strain. The distinct polymer components of biofilms are known to provide chemical protection, but little is known about how distinct extracellular polysaccharides may also protect biofilms against mechanical stresses such as shear or phagocytic engulfment. Decades-long infections of Pseudomonas. aeruginosa biofilms in the lungs of cystic fibrosis patients are natural models for studies of biofilm fitness under pressure from antibiotics and the immune system. In cystic fibrosis infections, production of the extracellular …

Phlpp Regulates Hexokinase 2-Dependent Glucose Metabolism In Colon Cancer Cells, Xiaopeng Xiong, Yang-An Wen, Mihail I. Mitov, Mary C. Oaks, Shigeki Miyamoto, Tianyan Gao

Markey Cancer Center Faculty Publications

Increased glucose metabolism is considered as one of the most important metabolic alterations adapted by cancer cells in order to generate energy as well as high levels of glycolytic intermediates to support rapid proliferation. PH domain leucine-rich repeat protein phosphatase (PHLPP) belongs to a novel family of Ser/Thr protein phosphatases that function as tumor suppressors in various types of human cancer. Here we determined the role of PHLPP in regulating glucose metabolism in colon cancer cells. Knockdown of PHLPP increased the rate of glucose consumption and lactate production, whereas overexpression of PHLPP had the opposite effect. Bioenergetic analysis using Seahorse …

Crispr-Cas9 Mediated Nox4 Knockout Inhibits Cell Proliferation And Invasion In Hela Cells, Naser Jafari, Hyunju Kim, Rackhyun Park, Liqing Li, Minsu Jang, Andrew J. Morris, Junsoo Park, Cai Huang

Markey Cancer Center Faculty Publications

Increased expression of NOX4 protein is associated with cancer progression and metastasis but the role of NOX4 in cell proliferation and invasion is not fully understood. We generated NOX4 knockout HeLa cell lines using the CRISPR-Cas9 gene editing system to explore the cellular functions of NOX4. After transfection of CRISPR-Cas9 construct, we performed T7 endonuclease 1 assays and DNA sequencing to generate and identify insertion and deletion of the NOX4 locus. We confirmed the knockout of NOX4 by Western blotting. NOX4 knockout cell lines showed reduced cell proliferation with an increase of sub-G1 cell population and the decrease of S/G2/M …