Medical Cell Biology Commons^™

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 …

Safety And Efficacy Of Silver-Coated Biomaterials In Vivo, Megan Klem, Darien L. Seidman, Rahyan Mahmoud, Manuella Adu, Lei Yu, Jeffrey Hettinger, Renee M Demarest

Rowan-Virtua Research Day

Overtreatment and overuse of antibiotics in healthcare and agricultural settings have contributed to the selective pressure on bacterial strains to develop resistance. Resistance can develop as a result of mutations and subsequent resistance genes that allow bacteria to survive against antibiotics. Novel silver-oxide coatings were developed and were previously demonstrated to prevent adhesion of gram-negative bacteria (Escherichia Coli and Pseudomonas Aeruginosa) to the disc, but did not prevent gram-positive bacterial adherence (Streptococcus Aureus). In order to determine whether the silver-oxide coatings are bacterial static and may be preventing progression to biofilm formation, in vivo analysis of S. Aureus attached to …

The Role Of Corticothalamic Projections (Prelimbic Cortex To Nucleus Reuniens) In Working Memory, Phillip Kumpf, Paul C. Kumpf, S. D. Dunn, Evan Ciacciarelli, T. Gohar, Timothy Sloand, Mark Niedringhaus, Elizabeth West

Rowan-Virtua Research Day

Working memory (WM) is the ability to store information for short periods of time and is used to execute tasks

WM has been understood to work via the medial prefrontal cortex (mPFC) and dorsal hippocampus (dHPC), but they do not directly project to each other

The nucleus reuniens of the thalamus (Re) is a “middle man” between the mPFC and dHPC

There are projections between the prelimbic cortex (PrL) and Re that may be used during WM

To test the connection of the PrL to Re, a delayed nonmatch to position (DNMTP) task was performed

The Brodmann Area 39/40 Of The Brain In Alzheimer’S, Mild Cognitive Impairment, And No Cognitive Impairment Subjects At Advanced Age Demonstrate Comparable Levels Of Blood-Brain Barrier Breach, Dhara Rana, Forum Mangrola, Randel L. Swanson, Venkat Venkataraman, David A. Bennett, Zoe Arvanitakis, David Libon, Robert Nagele, Nimish Acharya

Rowan-Virtua Research Day

• Alzheimer’s disease (AD) is one of the most common form of dementia

• Mild cognitive impairment (MCI), specifically amnestic subtype, more likely to progress to AD

• Pathogenesis Theories:

• o Accumulation of amyloid-beta peptides and neurofibrillary tangles containing hyperphosphorylated neuronal tau protein
• o Blood Brain Barrier (BBB) dysfunction is associated with AD pathogenesis

• Brodmann area 39/40: regions of parietal cortex are responsible for language, spatial cognition, memory retrieval, attention, phonological processing, and emotional processing

• Hypothesis: An increased BBB permeability in Brodmann area 39/40 of AD and age-matched MCI and no cognitive impairment (NCI) subjects

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 …

Bacille Calmette-Guérin Vaccine Reprograms Human Neonatal Lipid Metabolism In Vivo And In Vitro, Joann Diray-Arce, Asimenia Angelidou, Kristoffer Jarlov Jensen, Maria Giulia Conti, Rachel S Kelly, Matthew Pettengill, Mark Liu, Simon D Van Haren, Scott D Mcculloch, Greg Michelloti, Olubukola Idoko, Tobias R Kollmann, Beate Kampmann, Hanno Steen, Al Ozonoff, Jessica Lasky-Su, Christine S Benn, Ofer Levy

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Vaccines have generally been developed with limited insight into their molecular impact. While systems vaccinology enables characterization of mechanisms of action, these tools have yet to be applied to infants, who are at high risk of infection and receive the most vaccines. Bacille Calmette-Guérin (BCG) protects infants against disseminated tuberculosis (TB) and TB-unrelated infections via incompletely understood mechanisms. We employ mass-spectrometry-based metabolomics of blood plasma to profile BCG-induced infant responses in Guinea-Bissau in vivo and the US in vitro. BCG-induced lysophosphatidylcholines (LPCs) correlate with both TLR-agonist- and purified protein derivative (PPD, mycobacterial antigen)-induced blood cytokine production in vitro, raising the …

The Future Of Targeted Kinase Inhibitors In Melanoma, Signe Caksa, Usman Baqai, A E Aplin

Department of Cancer Biology Faculty Papers

Melanoma is a cancer of the pigment-producing cells of the body and its incidence is rising. Targeted inhibitors that act against kinases in the MAPK pathway are approved for BRAF-mutant metastatic cutaneous melanoma and increase patients' survival. Response to these therapies is limited by drug resistance and is less durable than with immune checkpoint inhibition. Conversely, rare melanoma subtypes have few therapeutic options for advanced disease and MAPK pathway targeting agents show minimal anti-tumor effects. Nevertheless, there is a future for targeted kinase inhibitors in melanoma: in new applications such as adjuvant or neoadjuvant therapy and in novel combinations with …

Applying Mci-062, A Novel Pan-Ras Inhibitor, To Treat Kras-Mutant Lung Cancer., Richard Fu

Poster Presentations

Honors thesis poster presentation.

RAS, one of the most prevalent oncogenes, is mutated in 27% of human cancers. Gainof- function RAS mutations activate multiple downstream pathways, including the RASRAF- MEK-ERK and PI3K/AKT/mTOR pathways, which are critical in tumorigenesis and cancer cell proliferation. The RAS proteins KRAS, HRAS, and NRAS along with their downstream effectors are attractive targets for cancer therapy since they act as frequent drivers in lung, colorectal, and pancreatic cancers. However, RAS proteins have relatively smooth surfaces that lack traditional binding pockets, making inhibitors specific to RAS difficult to create. Recently, a novel small molecule pan-RAS inhibitor named …

A Patient-Derived Ipsc Model To Study Glutamate Deficiency By Shank-3 Mutation In Autism Spectrum Disorder, Tiffany Berry, Courtney Caccia

Biology Student Scholarship

Tiffany Berry ’22, Majors: Biology and Psychology

Courtney Caccia ’22, Majors: Biology and Psychology

Faculty Mentor: Dr. Charles Toth, Biology

The use of human stem cell lines derived from persons with Autism Spectrum Disorder (ASD) provides a unique opportunity to model brain growth and potential to regain brain activity for treatment. Our lab has previously used stem cells to derive 3D cardiomyocytes to examine cardiovascular disease as well as kidney organoids and macrophages to study kidney disease. Using techniques our lab has learned using these stem cell models have prepared us to examine cell communication in mutated neurons. We will …

The Effects Of Paclitaxel On Cellular Migration And The Cytoskeleton, Ashley Salguero-Gonzalez

Thinking Matters Symposium

In a clinical setting, some patients are exposed to an anti-cancer chemotherapy agent, paclitaxel. Cancerous cells undergo rapid, continuous cell division without control. Chemotherapy treatments try to slow and stop the uncontrollable cell division cycles and eliminate cancerous cells in the process. Paclitaxel serves as a treatment for some types of cancers, including lung, melanoma, bladder, and esophageal. Because it targets the cytoskeleton, paclitaxel can also influence cell migration. This project utilizes a cellular migration assay and an immunohistochemistry assay to analyze the effects of paclitaxel on the movement of cells and on the cytoskeleton of neuroglia rat cells with …

Making Invisible Rna Visible: Discriminative Sequencing Methods For Rna Molecules With Specific Terminal Formations, Megumi Shigematsu, Yohei Kirino

Computational Medicine Center Faculty Papers

Next generation sequencing of RNA molecules (RNA-seq) has become a common tool to characterize the expression profiles of RNAs and their regulations in normal physiological processes and diseases. Although increasingly accumulating RNA-seq data are widely available through publicly accessible sites, most of the data for short non-coding RNAs (sncRNAs) have been obtained for microRNA (miRNA) analyses by standard RNA-seq, which only capture the sncRNAs with 5′-phosphate (5′-P) and 3′-hydroxyl (3′-OH) ends. The sncRNAs with other terminal formations such as those with a 5′-hydroxyl end (5′-OH), a 3′-phosphate (3′-P) end, or a 2′,3′-cyclic phosphate end (2′,3′-cP) cannot be efficiently amplified and …

Impact Of Interleukin-34 On The Promotion Of Bone Osteolysis And Neuroinflammation In Experimental Models Of Alzheimer’S Disease, Anny Ho

All HCAS Student Capstones, Theses, and Dissertations

Alzheimer’s disease (AD) is a growing health concern and is the most common type of dementia worldwide. Emerging evidence indicates that aggregated amyloid-beta (Aβ) peptides, one of the hallmark features of AD neuropathology, can increase RANKL-mediated osteoclast activity leading to the prevalence and severity of inflammatory osteolysis, e.g., osteoporosis and periodontal bone loss. Conversely, osteolytic lesions are associated with increased risk of dementia diagnosis indicating that there is a direct link between dementia and inflammatory osteolysis. It was demonstrated that the neuronal cells primarily produce interleukin-34 (IL-34) and microglia, macrophages, and osteoclast precursors express colony-stimulating factor 1 receptor (CSF-1R), a …

Ocular Adnexal Metastases From Renal Cell Carcinoma: An Update And Comprehensive Literature Review, Tejal Magan, Tejus Pradeep, Madalina Tuluc, Jurij R. Bilyk, Tatyana Milman

Wills Eye Hospital Papers

PURPOSE: The purpose of this study was to review the clinical presentation, systemic work-up, and outcomes of all previously reported ocular adnexal (OA) metastases from renal cell carcinoma (RCC). METHODS: This was a literature review. PubMed and Google Scholar databases were searched for all well-documented cases of OA metastases from RCC. RESULTS: Final analysis identified 44 patients with either biopsy-confirmed (41/44, 93%) or treatment response-documented (3/44, 6%) OA metastases from RCC. Thirty-four (77%) patients were male. The median age was 60 years (mean: 60, range: 22-87 years). The most common presenting signs were proptosis (19/44, 43%) and OA mass (14/44, …

Gm1 Ganglioside Modifies Microglial And Neuroinflammatory Responses To Α-Synuclein In The Rat Aav-A53t Α-Synuclein Model Of Parkinson's Disease, Jay S Schneider, Garima Singh, Courtney K. Williams, Vikrant Singh

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Among the pathological events associated with the dopaminergic neurodegeneration characteristic of Parkinson's disease (PD) are the accumulation of toxic forms of α-synuclein and microglial activation associated with neuroinflammation. Although numerous other processes may participate in the pathogenesis of PD, the two factors mentioned above may play critical roles in the initiation and progression of dopamine neuron degeneration in PD. In this study, we employed a slowly progressing model of PD using adeno-associated virus-mediated expression of human A53T α-synuclein into the substantia nigra on one side of the brain and examined the microglial response in the striatum on the injected side …

Acute Oxygen-Sensing Via Mitochondria-Generated Temperature Transients In Rat Carotid Body Type I Cells, Ryan J. Rakoczy, Clay M. Schiebrel, Christopher N. Wyatt

Neuroscience, Cell Biology & Physiology Faculty Publications

The Carotid Bodies (CB) are peripheral chemoreceptors that detect changes in arterial oxygenation and, via afferent inputs to the brainstem, correct the pattern of breathing to restore blood gas homeostasis. Herein, preliminary evidence is presented supporting a novel oxygen-sensing hypothesis which suggests CB Type I cell “hypoxic signaling” may in part be mediated by mitochondria-generated thermal transients in TASK-channel-containing microdomains. Distances were measured between antibody-labeled mitochondria and TASK-potassium channels in primary rat CB Type I cells. Sub-micron distance measurements (TASK-1: 0.33 ± 0.04 µm, n = 47 vs TASK-3: 0.32 ± 0.03 µm, n = …

Investigating The Role Of The Basolateral Amygdala Plays In The Incubation Of Cue-Induced Cocaine Seeking Behavior, Claire Marie Corbett

Graduate School of Biomedical Sciences Theses and Dissertations

Cocaine use disorder is a chronic, relapsing brain disease. Sex and ovarian hormones are known to influence cocaine addiction liability and relapse vulnerability. However, little is known regarding the cellular and synaptic mechanisms contributing to sex differences in relapse vulnerability, including how these measures are influenced by hormonal fluctuations. To investigate sex differences in relapse vulnerability we use a rodent model of cocaine craving and relapse called the incubation model in which cue-induced seeking progressively increases or “incubates” during the first month of withdrawal from extended-access cocaine self-administration. Using this model, we have recently shown that females in the estrus …

The Center Of Vaccine Controversy: Wi-38 Cells, Courtney S. Chau

Classical Conversations

Throughout history, there exists no bigger killer than disease. For centuries, families have fought against sickness and death, and ancient culture has spent thousands of years developing their own methods for healing. In the most recent years, the field of medicine has greatly expanded, allowing for cures and medicine to be greatly distributed to the general public. Millions of lives have been saved, and today society can live without fear of lurking diseases snatching away loved ones with a blink of an eye. This senior thesis focuses on the development of vaccines made from the WI-38 cell line. This cell …

Investigation Of Oncogenic Ras And Endoplasmic Reticulum-Mitochondria Calcium Flux And Their Relationship In The Context Of Tumorigenesis, Emma Anderson

Senior Honors Theses

Intracellular calcium as a signaling molecule is a pervasive feature of cellular pathways, especially those that manage internal homeostasis and transitions through the cell cycle, so much so that regulated, responsive calcium flux between the endoplasmic reticulum (ER) and the mitochondria has been suggested to play a major role in cancer development. Another factor commonly implicated in tumorigenesis is RAS, an oncogene that controls signaling for many pathways that are also regulated by calcium. While both calcium and oncogenic RAS signaling are implicated in cancer development, possible links between them have yet to be determined. The identification of these links …

Patterns Of Crystallin Gene Expression In Differentiation State Specific Regions Of The Embryonic Chicken Lens, Zhiwei Ma, Daniel Chauss, Joshua Disatham, Xiaodong Jiao, Lisa Ann Brennan, A Sue Menko, Marc Kantorow, J Fielding Hejtmancik

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Purpose: Transition from lens epithelial cells to lens fiber cell is accompanied by numerous changes in gene expression critical for lens transparency. We identify expression patterns of highly prevalent genes including ubiquitous and enzyme crystallins in the embryonic day 13 chicken lens.

Methods: Embryonic day 13 chicken lenses were dissected into central epithelial cell (EC), equatorial epithelial cell (EQ), cortical fiber cell (FP), and nuclear fiber cell (FC) compartments. Total RNA was prepared, subjected to high-throughput unidirectional mRNA sequencing, analyzed, mapped to the chicken genome, and functionally grouped.

Results: A total of 77,097 gene-specific transcripts covering 17,450 genes were expressed, …

Mitophagy-Mediated Regulation Of Ros Homeostasis During Hsc Activation Contributes To Cell Fate, Amber Lynne Smith

Theses and Dissertations (ETD)

The ability of hematopoietic stem cells to self-renew and differentiate is required for the maintenance of all blood lineages under basal physiologic conditions and in response to inflammatory stress. The degradative capacity of the autophagy-lysosomal system is a determinant of hematopoietic stem cell (HSC) activation status with low autophagy predicting activation of HSCs, and autophagy deficiency causing the spontaneous loss of quiescence and HSC exhaustion. Although an increase in mitochondrial activity has been suggested as the cause of HSC depletion in autophagy-defective models, the contribution of mitophagy to HSC function remains to be elucidated. Here, we capitalized on the observation …