Cell Biology Commons^™

Bio-Vascular 3d, Wisdom Shadrach

ORBioM (Open Research BioSciences Meeting)

Cardiovascular disease is a leading cause of mortality and morbidity across the world and according to the world health organization account for 32% of mortality rate globally. There still remain a need to develop better in vitro vascular models that would aid further in-depth understanding of cardiovascular pathogenesis and proposed therapeutic intervention.

This study intends to characterize four novel medically relevant synthetic polymer scaffolds, and one hydrogel, for their biocompatibility and potential application in a tissue engineered blood vessel (TEBV). A primary human endothelial cell line derived from the vein of the umbilical cord (HUVEC), and a human primary smooth …

Short Chain Fatty Acid Combination Treatment Protects Against 6-Ohda Induced Decrease In Neurite Growth In An In Vitro Model Of Parkinson’S Disease., Alex Morris

ORBioM (Open Research BioSciences Meeting)

Title: Short chain fatty acid combination treatment protects against 6-OHDA induced decrease in neurite growth in an in vitro model of Parkinson’s disease.

Authors: Alex Morris¹, Louise M. Collins^1,2,3, Gerard W. O’Keeffe², Caitriona M. Guinane¹

¹ Department of Biological Sciences, Munster Technological University (MTU), Cork, Ireland.

² Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.

³ Department of Physiology, University College Cork, Cork, Ireland.

Background: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron degeneration. This leads to motor dysfunction which is accompanied by gastrointestinal comorbidities such as constipation …

Ciliogenesis Mechanisms Mediated By Pak2-Arl13b Signaling In Brain Endothelial Cells Is Responsible For Vascular Stability, Karthikeyan Thirugnanam, Shubhangi Prabhudesai, Emma Van Why, Amy Pan, Ankan Gupta, Koji Foreman, Rahima Zennadi, Kevin R. Rarick, Surya M. Nauli, Sean P. Palacek, Ramani Ramchandran

Pharmacy Faculty Articles and Research

In the developing vasculature, cilia, microtubule-based organelles that project from the apical surface of endothelial cells (ECs), have been identified to function cell autonomously to promote vascular integrity and prevent hemorrhage. To date, the underlying mechanisms of endothelial cilia formation (ciliogenesis) are not fully understood. Understanding these mechanisms is likely to open new avenues for targeting EC-cilia to promote vascular stability. Here, we hypothesized that brain ECs ciliogenesis and the underlying mechanisms that control this process are critical for brain vascular stability. To investigate this hypothesis, we utilized multiple approaches including developmental zebrafish model system and primary cell culture systems. …

The Effect Of Fibrodysplasia Ossificans Progressiva On The Tongue, Amy Backal, Amanda Harrop, David J. Goldhamer Dr.

University Scholar Projects

FOP is a rare genetic disorder in which skeletal muscle and associated connective tissue progressively turn to bone through a process called heterotopic ossification (HO). The extra skeletal bone growth is cumulative, eventually trapping patients in a second skeleton that eventually leads to death by asphyxiation. The FOP mutation is autosomal dominant that can be inherited or acquired sporadically. Unfortunately, FOP is currently incurable with no therapeutic options to inhibit bone growth or reduce existing bone nodules. My project intends to further our understanding of the cellular mechanisms of the disease within the tongue muscle. A population of cells known …

The Effect Of Fibrodysplasia Ossificans Progressiva On The Tongue, Amy Backal, Amanda Harrop, David J. Goldhamer Dr.

Honors Scholar Theses

FOP is a rare genetic disorder in which skeletal muscle and associated connective tissue progressively turn to bone through a process called heterotopic ossification (HO). The extra skeletal bone growth is cumulative, eventually trapping patients in a second skeleton that eventually leads to death by asphyxiation. The FOP mutation is autosomal dominant that can be inherited or acquired sporadically. Unfortunately, FOP is currently incurable with no therapeutic options to inhibit bone growth or reduce existing bone nodules. My project intends to further our understanding of the cellular mechanisms of the disease within the tongue muscle. A population of cells known …

Resolving The Repression Pathway Of Virulence Gene Hila In Salmonella, Alexandra King, Lon Chubiz Phd, Brenda Pratte, Lauren Daugherty

Undergraduate Research Symposium

Salmonella is a relatively abundant, virulent species of bacteria that is most known for spreading gastrointestinal diseases through food. These illnesses result in approximately 1.35 million infections, including over 25,000 hospitalizations each year, in the U.S. alone (CDC.gov). As antibiotic resistance becomes an increasingly urgent public health problem, the importance of developing alternative treatment methods is only becoming more crucial. One of the genes responsible for this virulence is known as hilA. HilA is the main transcriptional regulator of Salmonella Pathogenicity Island-1 gene (UniProt). SPI-1 plays an important role in the invasion of Salmonella into epithelial cells. The proteins encoded …

Cdc6 Is Sequentially Regulated By Pp2a-Cdc55, Cdc14, And Sic1 For Origin Licensing In S. Cerevisiae, Jasmin Philip

Dissertations, Theses, and Capstone Projects

Control of DNA replication is critical for progression of the cell cycle and genomic stability. Cyclin-dependent kinases (CDKs) coordinate numerous phosphorylation events to accomplish two biological tasks for all living organisms: DNA replication and cell division. One CDK, Cyclin-Cdc28, is responsible for cell cycle progression in budding yeast. DNA replication requires a stepwise assembly of the pre-replicative complex on DNA, including Orc1-6, Cdc6, Cdt1 and Mcm2-7, during M-G1 phase. Cdc6 contains eight Cdc28 consensus sites, SP or TP motifs. Clb5-Cdc28 phosphorylates Cdc6-T7 to recruit Cks1, the Cdc28 phospho-adaptor, for subsequent multisite phosphorylation during S phase. There are two phospho-degrons at …

Comparative Studies Between The Murine Immortalized Brain Endothelial Cell Line (Bend.3) And Induced Pluripotent Stem Cell-Derived Human Brain Endothelial Cells For Paracellular Transport, Jiahong Sun, Weijun Ou, Derick Han, Annlia Paganini-Hill, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Brain microvascular endothelial cells, forming the anatomical site of the blood-brain barrier (BBB), are widely used as in vitro complements to in vivo BBB studies. Among the immortalized cells used as in vitro BBB models, the murine-derived bEnd.3 cells offer culturing consistency and low cost and are well characterized for functional and transport assays, but result in low transendothelial electrical resistance (TEER). Human-induced pluripotent stem cells differentiated into brain microvascular endothelial cells (ihBMECs) have superior barrier properties, but the process of differentiation is time-consuming and can result in mixed endothelial-epithelial gene expression. Here we performed a side-by-side comparison of the …

Noxious Cellular Injury Triggers An Oxidative Stress Gene Response, Shawyun Khoshneviszadeh

Master of Science in Integrative Biology Theses

Wound and regeneration involves a series of complex processes that can induce oxidative stress by elevating intracellular reactive oxygen species (ROS) levels. In this study, we used RNA-seq and qPCR to examine the molecular signature of Human Embryonic Kidney cells (HEK-293T) stimulated with Crotalus atrox (CA) venom. NGS data was assembled and annotated utilizing the Illumina paired-end RNA-seq approach with software packages HISAT2 and StringTie. Results showed 243 genes were differentially expressed (106 upregulated, 137 downregulated) between CA venom stimulated and non-stimulated cells (p<0.05). HEK-293T stimulated with CA venom for 4 hours showed an increase in the expression of oxidative stress response genes (e.g., TOMM6, EGR (1,2,3), HSP70 (1A, 1B), SPRY4, ETV5, and EMP1) (Fold-Change (fc) >2.0). Significantly downregulated genes were associated with many novel transcripts/proteins such as AC117378, AD000671, and AC023509. …

Du Undergraduate Showcase: Research, Scholarship, And Creative Works: Abstracts, Emma Aggeler, Elena Arroway, Daisy T. Booker, Justin Bravo, Kyle Bucholtz, Megan Burnham, Nicole Choi, Spencer Cockerell, Rosie Contino, Jackson Garske, Kaitlyn Glover, Caroline Hamilton, Haley Hartmann, Madalyne Heiken, Colin Holter, Leah Huzjak, Alyssa Jeng, Cole Jernigan, Chad Kashiwa, Adelaide Kerenick, Emily King, Abigail Langeberg, Maddie Leake, Meredith Lemons, Alec Mackay, Greer Mckinley, Ori Miller, Guy Milliman, Katherine Miromonti, Audrey Mitchell, Lauren Moak, Megan Morrell, Gelella Nebiyu, Zdenek Otruba, Toni V. Panzera, Kassidy Patarino, Sneha Patil, Alexandra Penney, Kevin Persky, Caitlin Pham, Gabriela Recinos, Mary Ringgenberg, Chase Routt, Olivia Schneider, Roman Shrestha, Arlo Simmerman, Alec Smith, Tessa Smith, Nhi-Lac Thai, Kyle Thurmann, Casey Tindall, Amelia Trembath, Maria Trubetskaya, Zachary Vangelisti, Peter Vo, Abby Walker, David Winter, Grayden Wolfe, Leah York

DU Undergraduate Research Journal Archive

Abstracts from the DU Undergraduate Showcase.

The Effect Of The Oncometabolite Fumarate In The Response To Dna Damage: An Analysis Of The Role Of Fumarate In The Response Of Cells A2780 To Dna Damage Induced By Cisplatin, Gillian Luczyk, Luisa María Sierra, Enol Álvarez González

DU Undergraduate Research Journal Archive

Previous research has been conducted on the effect of oncometabolites on DNA damage repair; however, these studies have traditionally focused on the response to damage caused by DNA double-strand breaks, whereas this study involves cisplatin-induced damage that creates DNA cross-links. This study reports on the effect of the oncometabolite fumarate on the response of A2780 cells to DNA damage produced by cisplatin. Three assays were used to complete this study: comet assay, cell cycle assay and apoptosis assay. The comet assay revealed that fumarate influenced the response of cells to DNA damage and, at a lower 1mM concentration, appeared to …

Assembly Of The Peripheral Arm Subunits Of Escherichia Coli Complex I And Analysis Of Clinical Mutations, Hind Alkhaldi

Biological Sciences Theses and Dissertations

Respiratory Complex I from E. coli is a proto-type of the mitochondrial enzyme, consisting of a 6-subunit peripheral arm (B-CD-E-F-G-I) and a 7-subunit membrane arm. When subunits E-F-G (N-module), were expressed alone they formed an active complex as determined by co-immunoprecipitation and native gel electrophoresis. When co-expressed with subunits B and CD, only a complex of E-F-G was found. When these five subunits were co-expressed with subunit I and two membrane subunits, A and H, a complex of B-CD-E-F-G-I was membrane-bound, constituting the N- and Q-modules. Assembly of Complex I was also followed by splitting the genes between two plasmids, …

A Neuromuscular Look Into Genetics Of Muscle Aging, Christina Talley

Master of Science in Integrative Biology Theses

As individuals age throughout their life, they experience muscle tissue loss that impacts their quality of life such as a decrease in their physical capabilities and sometimes even their mental capacity. The process of muscle aging is the key point of this study. This involves the individual’s muscles and the motor neurons that control them. Skeletal muscles are used daily to maintain posture, stand, walk, etc. Throughout a lifetime these muscles undergo damage and need to be repaired. When the muscles are repaired, they express physical changes. The tissue shrinks in size and eventually the composition of the tissue is …

Mechanisms Of Sorting And Fission At The Endosomes, Kanika Dhawan

Theses & Dissertations

Endocytic trafficking is a fundamental cellular process that regulates the transport of lipids and proteins. Our lab focuses on the intracellular trafficking of receptors involved in cellular processes such as cell division, migration, and proliferation. Accordingly, the regulation of these trafficking pathways is tightly controlled, involving a complex series of events, of which a key step is the endosomal fission. Perturbations in the endosomal network can eventually lead to impaired receptor recycling to the plasma membrane (PM) and, therefore, have pathological consequences like Alzheimer’s disease and multiple cancers. Upon internalization, cargo-laden vesicles released from the PM fuse with the sorting …

Characterization Of 1,1-Diarylethylene Foxm1 Inhibitors Against High-Grade Serous Ovarian Carcinoma Cells, Cassie Liu

Theses & Dissertations

Forkhead box M1 (FOXM1) is a member of the conserved forkhead box (FOX) transcription factor family. Over the last two decades, FOXM1 has emerged as a multifunctional oncoprotein and a robust biomarker of poor prognosis in many human malignancies. FOXM1 and its associated oncogenic transcriptional signature are enriched in >85% of ovarian cancer cases, and FOXM1 expression and activity can be enhanced by a plethora of genomic, transcriptional, post-transcriptional, and post-translational mechanisms. As a master transcriptional regulator, FOXM1 promotes critical oncogenic phenotypes in ovarian cancer, including: (1) cell proliferation, (2) invasion and metastasis, (3) chemotherapy resistance, (4) cancer stem cell …

Sox2 Dosage Governs Tumor Cell Identity And Proliferation, Ethan P. Metz

Theses & Dissertations

The stem cell transcription factor SOX2 has been widely recognized for its critical roles during mammalian development. SOX2 expression has also been implicated in more than 20 types of human cancers. Importantly, the expression of SOX2 is regulated at multiple levels, which enables the tight regulation of SOX2 levels. Previous work from our laboratory has shown that elevating SOX2 from an inducible promoter inhibits the proliferation of several human tumor cell types. Other studies have reported that high levels of SOX2 are necessary to maintain lineage plasticity in advanced tumors. Thus, the dosage of SOX2 plays a critical role in …

Novel Molecular Mechanisms Of C-Terminal Eps15 Homology Domain (Ehd) Proteins In Endocytic Trafficking And Primary Ciliogenesis, Tyler M. Jones

Theses & Dissertations

Endocytic membrane trafficking is a key cellular process that is critical for regulating the transport of internalized cargoes such as lipids and receptors. Our lab focuses on understanding the mechanisms and cellular functions of the proteins that regulate this pathway. One family of proteins that has seen significant interest over recent years is the C-terminal Eps15 Homology Domain (EHD) family of proteins. Mammalians have four EHD paralogs (EHD1-4) that are expressed ubiquitously in tissues. These proteins have distinct yet overlapping functions in regulating endocytic pathways. EHD1 has been shown to induce constriction and is recruited to induce fission of tubular …

Determining The Role Of Mir-133a In The Diabetic Heart, Tyler Kambis

Theses & Dissertations

Diabetes mellitus (DM) is characterized by hyperglycemia, hyperlipidemia, and hypoinsulemia, each of which disrupt intracellular mechanisms in the heart. DM is a chronic metabolic disease delineated into two categories: insulin deficient-type 1 DM and insulin resistant-type 2 DM. Although they differ in underlying genetic and physiological factors, both significantly increase the risk of heart failure. Impaired insulin signaling shifts energy dependency from glycolysis towards fatty acid β-oxidation in the DM heart. This DM-induced metabolic shift increases mitochondrial stress leading to mitochondrial dysfunction and cell death in the heart. The metabolically entwined ferroptosis is a novel form of myocardial cell death …

Cdk8 Kinase Module Modifies Expression Of Specific Translation-Related Proteins Before And After Stress, Brittany Friedson, Katrina Cooper

Rowan-Virtua Research Day

Translation is tightly coupled to growth status. Efficient protein synthesis is necessary for cell growth in nutrient rich environments, while global translation inhibition combined with selective translation of stress-responsive mRNAs helps limit growth in times of stress. Environmental stress cues which inhibit the nutrient-sensing complex TORC1 are known to reduce general translation, but how does the cell alter protein synthesis machinery to adapt to these conditions? A few mechanisms to promote cell survival in nitrogen starvation include post-translational modification and selective degradation of specific mRNA-binding translation factors, as well as inhibition of activators of genes whose products are required for …

Examining Levels Of Catecholamine Neurotransmitter Regulatory Proteins Within The Prefrontal Cortex Of Rodents Following Traumatic Brain Injury, Eleni Papadopoulos, Christopher P. Knapp, Claire M. Corbett, Jessica Loweth, Rachel L. Navarra

Rowan-Virtua Research Day

Traumatic brain injury (TBI) resulting from impact to the head can cause long lasting impairments of cognitive processes that lead to increased risk-taking behavior in clinical populations. Our laboratory has recently shown that female, but not age-matched male, rats increase preference for risky choices after multiple experimentally-induced mild TBI’s. Our overarching goal is to understand the neural mechanisms underlying TBI-induced increases in risk-taking behavior.

The prefrontal cortex (PFC) plays a prominent role in risk-based decision making. Sub[1]regions of the PFC include the medial PFC (mPFC), the orbitofrontal cortex (OFC), and the anterior cingulate cortex (ACC), and these sub[1]regions play specific …