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Articles 1 - 30 of 272
Full-Text Articles in Life Sciences
Maackia Amurensis Seed Lectin (Masl) And Soluble Human Podoplanin (Shpdpn) Sequence Analysis And Effects On Human Oral Squamous Cell Carcinoma (Oscc) Cell Migration And Viability, Ariel C Yin, Cayla J Holdcraft, Eamonn J Brace, Tyler J Hellmig, Sayan Basu, Saumil Parikh, Katarzyna Jachimowska, Evelyne Kalyoussef, Dylan Roden, Soly Baredes, Eugenio M Capitle, David I Suster, Alan J Shienbaum, Caifeng Zhao, Haiyan Zheng, Kevin Balcaen, Simon Devos, Jurgen Haustraete, Mahnaz Fatahzadeh, Gary S Goldberg
Maackia Amurensis Seed Lectin (Masl) And Soluble Human Podoplanin (Shpdpn) Sequence Analysis And Effects On Human Oral Squamous Cell Carcinoma (Oscc) Cell Migration And Viability, Ariel C Yin, Cayla J Holdcraft, Eamonn J Brace, Tyler J Hellmig, Sayan Basu, Saumil Parikh, Katarzyna Jachimowska, Evelyne Kalyoussef, Dylan Roden, Soly Baredes, Eugenio M Capitle, David I Suster, Alan J Shienbaum, Caifeng Zhao, Haiyan Zheng, Kevin Balcaen, Simon Devos, Jurgen Haustraete, Mahnaz Fatahzadeh, Gary S Goldberg
Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship
Maackia amurensis lectins serve as research and botanical agents that bind to sialic residues on proteins. For example, M. amurensis seed lectin (MASL) targets the sialic acid modified podoplanin (PDPN) receptor to suppress arthritic chondrocyte inflammation, and inhibit tumor cell growth and motility. However, M. amurensis lectin nomenclature and composition are not clearly defined. Here, we sought to definitively characterize MASL and its effects on tumor cell behavior. We utilized SDS-PAGE and LC-MS/MS to find that M. amurensis lectins can be divided into two groups. MASL is a member of one group which is composed of subunits that form dimers, …
Trna Anticodon Cleavage By Target-Activated Crispr-Cas13a Effector, Ishita Jain, Matvey Kolesnik, Konstantin Kuznedelov, Leonid Minakhin, Natalia Morozova, Anna Shiriaeva, Alexandr Kirillov, Sofia Medvedeva, Alexei Livenskyi, Laura Kazieva, Kira S Makarova, Eugene V Koonin, Sergei Borukhov, Konstantin Severinov, Ekaterina Semenova
Trna Anticodon Cleavage By Target-Activated Crispr-Cas13a Effector, Ishita Jain, Matvey Kolesnik, Konstantin Kuznedelov, Leonid Minakhin, Natalia Morozova, Anna Shiriaeva, Alexandr Kirillov, Sofia Medvedeva, Alexei Livenskyi, Laura Kazieva, Kira S Makarova, Eugene V Koonin, Sergei Borukhov, Konstantin Severinov, Ekaterina Semenova
Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship
Type VI CRISPR-Cas systems are among the few CRISPR varieties that target exclusively RNA. The CRISPR RNA–guided, sequence-specific binding of target RNAs, such as phage transcripts, activates the type VI effector, Cas13. Once activated, Cas13 causes collateral RNA cleavage, which induces bacterial cell dormancy, thus protecting the host population from the phage spread. We show here that the principal form of collateral RNA degradation elicited by Leptotrichia shahii Cas13a expressed in Escherichia coli cells is the cleavage of anticodons in a subset of transfer RNAs (tRNAs) with uridine-rich anticodons. This tRNA cleavage is accompanied by inhibition of protein synthesis, thus …
Targeting Tgf-Β During Epithelial-To-Mesenchymal Progression As An Effective Therapy Against Colorectal Cancer, Joyce Fan
Undergraduate Research
Colorectal cancer is one of the most common cancers worldwide. Understanding the mechanisms of colorectal cancer progression is crucial for the development of effective therapeutics. Epithelial-to-mesenchymal transition is a hallmark feature of cancer and is defined as the loss of epithelial cell features, such as apical-basal polarity and high expression of cell adhesion molecules, and the development of mesenchymal features, such as lack of polarity and increased cell mobility. Epithelial-to-mesenchymal is essential for cell migration, proliferation, and tumor growth. Both the TGF-β and SMAD pathway are associated with colorectal cancer progression. TGF-β is crucial to the cellular mechanism of cell …
The Frequency Of Pathogenic Variation In The All Of Us Cohort Reveals Ancestry-Driven Disparities, Eric Venner, Karynne Patterson, Divya Kalra, Marsha M Wheeler, Yi-Ju Chen, Sara E Kalla, Bo Yuan, Jason H Karnes, Kimberly Walker, Joshua D Smith, Sean Mcgee, Aparna Radhakrishnan, Andrew Haddad, Philip E Empey, Qiaoyan Wang, Lee Lichtenstein, Diana Toledo, Gail Jarvik, Anjene Musick, Richard A Gibbs
The Frequency Of Pathogenic Variation In The All Of Us Cohort Reveals Ancestry-Driven Disparities, Eric Venner, Karynne Patterson, Divya Kalra, Marsha M Wheeler, Yi-Ju Chen, Sara E Kalla, Bo Yuan, Jason H Karnes, Kimberly Walker, Joshua D Smith, Sean Mcgee, Aparna Radhakrishnan, Andrew Haddad, Philip E Empey, Qiaoyan Wang, Lee Lichtenstein, Diana Toledo, Gail Jarvik, Anjene Musick, Richard A Gibbs
Journal Articles
Disparities in data underlying clinical genomic interpretation is an acknowledged problem, but there is a paucity of data demonstrating it. The All of Us Research Program is collecting data including whole-genome sequences, health records, and surveys for at least a million participants with diverse ancestry and access to healthcare, representing one of the largest biomedical research repositories of its kind. Here, we examine pathogenic and likely pathogenic variants that were identified in the All of Us cohort. The European ancestry subgroup showed the highest overall rate of pathogenic variation, with 2.26% of participants having a pathogenic variant. Other ancestry groups …
On The Anti-Adipogenic Function Of Collagen Triple Helix Repeat-Containing Protein 1, Matthew E. Siviski
On The Anti-Adipogenic Function Of Collagen Triple Helix Repeat-Containing Protein 1, Matthew E. Siviski
Electronic Theses and Dissertations
Adipogenesis is regulated by the coordinated activity of adipogenic transcription factors, including PPAR-gamma (PPARG) and C/EBP alpha (CEBPA). Thus, dysregulated adipogenesis predisposes adipose tissues to adipocyte hypertrophy and hyperplasia. We have previously reported that mice possessing a homozygous null gene mutation in collagen triple helix repeat-containing protein 1 (CTHRC1) have increased adiposity compared to wildtype mice, supporting the concept that CTHRC1 regulates body composition. Herein, we investigated the anti-adipogenic activity of CTHRC1. Using 3T3-L1 preadipocytes, we showed significantly reduced adipogenic differentiation in the presence of CTHRC1 commensurate to marked suppression of Cebpa and Pparg gene expression. In addition, CTHRC1 increased …
Hematological Biomarkers Of Troponin, Neutrophil-To-Lymphocyte Ratio, And Monocyte-Tolymphocyte Ratio Serve As Effective Predictive Indicators Of High-Risk Mortality In Acute, Bryan Gervais De Liyis, Angela Faustine Ciaves, Marwa Humaira Intizam, Pierre Joshua Jusuf, I Made Junior Rina Artha
Hematological Biomarkers Of Troponin, Neutrophil-To-Lymphocyte Ratio, And Monocyte-Tolymphocyte Ratio Serve As Effective Predictive Indicators Of High-Risk Mortality In Acute, Bryan Gervais De Liyis, Angela Faustine Ciaves, Marwa Humaira Intizam, Pierre Joshua Jusuf, I Made Junior Rina Artha
BioMedicine
Background: Assessing high-risk mortality in acute coronary syndrome (ACS) patients, encompassing ST-Elevation Myocardial Infarction (STEMI), Non-ST-Elevation Myocardial Infarction (NSTEMI), and Unstable Angina Pectoris (UAP), is crucial. However, the prognostic significance of hematological parameters in predicting high-risk mortality in ACS patients remains uncertain despite advancements in ACS research. Aim: The aim was to investigate prognostic significance of hematological parameters troponin, Creatine Kinase-MB (CKMB), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Monocyte-to-Lymphocyte Ratio (MLR), Basophil-to-Lymphocyte Ratio (BLR), and Eosinophil-to-Lymphocyte Ratio (ELR) levels in predicting high-risk mortality in ACS patients. Methods: In this retrospective observational study, data from medical records of 115 patients with …
The Adaptor Protein P66shc Governs Central Nervous System Cell Metabolism And Resistance To Aβ Toxicity, Asad Lone
Electronic Thesis and Dissertation Repository
Alzheimer’s disease (AD), a progressive and irreversible neurodegenerative disorder, and is the leading cause of dementia worldwide. It has been posited that AD is caused by the gradual deposition of toxic amyloid-b (Ab) plaques in the brain- that cause oxidative stress and eventually leads to neuronal death and synaptic loss. However, multiple therapies that either interfere with the production, or enhance the removal of Ab from the brain, have ultimately failed to slow or prevent AD. With the ever-increasing burden of AD worldwide, there exists an urgent need for novel therapeutic targets. The adult human brain is an energy demanding …
Age-Related Morphofunctional Changes In Sickle Cell Mice Bone Marrow Mesenchymal Stromal Cells, Felipe Augusto Rós, Péricles Natan Mendes Da Costa, Jonathan Milhomens, Débora Glenda Lima De La-Roque, Fernanda Ursoli Ferreira, Juliana De Matos Maçonetto, Camila Cristina De Oliveira Menezes Bonaldo, Julianne Vargas De Carvalho, Patrícia Vianna Bonini Palmaa Palma, Wassim El Nemer, Dimas Tadeu Covas, Simone Kashima
Age-Related Morphofunctional Changes In Sickle Cell Mice Bone Marrow Mesenchymal Stromal Cells, Felipe Augusto Rós, Péricles Natan Mendes Da Costa, Jonathan Milhomens, Débora Glenda Lima De La-Roque, Fernanda Ursoli Ferreira, Juliana De Matos Maçonetto, Camila Cristina De Oliveira Menezes Bonaldo, Julianne Vargas De Carvalho, Patrícia Vianna Bonini Palmaa Palma, Wassim El Nemer, Dimas Tadeu Covas, Simone Kashima
Hematology/Oncology and Stem Cell Therapy
Bone marrow mesenchymal stromal cells (BM-MSC) are key elements of the hematopoietic niche and participate in the regulatory mechanisms of hematopoietic stem cells (HSC). Hematological diseases can affect MSCs and their functions. However, the dysregulations caused by sickle cell disease (SCD) are not fully elucidated. This work explored changes in BM-MSC and their relationship with age using sickle cell mice (Townes-SS). BM-MSC were isolated from Townes-SS, and control groups Townes-AA and C57BL/6J at 30- and 60-day-old. The BM-MSCs showed no morphological differences in culture and demonstrated the murine MSC-like immunophenotypic profile (Sca-1+, CD29+, CD44+, CD90.2+, CD31-, CD45- and CD117-). Subsequently, …
Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke
Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke
Electronic Theses and Dissertations
The number of daily bacterial infections is climbing and the CDC explains that this is due to the antibiotic-resistant threat in the United States. Finding a faster way of bacterial identification is necessary as it currently takes 1-4 days for a medical lab to culture and identify bacteria. Photoacoustic flow cytometry (PAFC) can be used as an alternative method resulting in swift identification within an hour (Edgar, 2019). Pseudomonas aeruginosa, cell line PA01, will be coated in up to a few hundred red dyed phages making it detectible by the photoacoustic flow cytometry system. Bacteriophages (phages) are viruses that …
Role Of Chronic Stress-Induced Neuroinflammation In Rodent Locus Coeruleus Physiology And Anxiety-Like Behaviors, Arthur Anthony Alfonso Reyes
Role Of Chronic Stress-Induced Neuroinflammation In Rodent Locus Coeruleus Physiology And Anxiety-Like Behaviors, Arthur Anthony Alfonso Reyes
Graduate School of Biomedical Sciences Theses and Dissertations
The locus coeruleus (LC), the primary site of brain norepinephrine (NE), is a key anatomical brain region implicated in the stress response. Stress is a neuroendocrine physiologic response to a stressor that promotes organism survival through adaptive change and restoration of homeostasis. The central stress response, which drives behavioral and physiological change, is primarily mediated by activating the hypothalamic-pituitary-adrenal (HPA) axis. While advantageous in the short term, chronic stress exposure can lead to HPA axis and LC dysregulation, which are thought to contribute to the etiology of anxiety disorders. Previous studies demonstrate the effects of acute stress in increasing LC …
Extravasated Brain-Reactive Autoantibodies Perturb Neuronal Surface Protein Expression In Alzheimer's Pathology, Wardah Bajwa, Mary Kosciuk, Randel L. Swanson, Anuradha Krishnan, Venkat Venkataraman, Robert Nagele, Nimish Acharya
Extravasated Brain-Reactive Autoantibodies Perturb Neuronal Surface Protein Expression In Alzheimer's Pathology, Wardah Bajwa, Mary Kosciuk, Randel L. Swanson, Anuradha Krishnan, Venkat Venkataraman, Robert Nagele, Nimish Acharya
Rowan-Virtua Research Day
Background: Increased blood-brain barrier (BBB) permeability is reported in both the neuropathological and in vivo studies in both Alzheimer’s Disease (AD) and age matched cognitively normal, no cognitive impairment (NCI), subjects. Impaired BBB allows various vascular components such as immunoglobulin G (IgG) to extravasate into the brain and specifically bind to various neuronal surface proteins (NSP), also known as brain reactive autoantibodies (BrABs). This interaction is predicted to further enhance deposition of amyloid plaques.
Hypothesis: Interaction between extravasated BrABs and its cognate NSPs lower the expression of that NSPs in AD patients.
Methods: We selected Western blotting technique to study …
The Involvement Of Ubiquitin In Med13 Cyclin C Degradation Following Cellular Stress, Ayesha Gurnani, Brittany Friedson, Katrina Cooper
The Involvement Of Ubiquitin In Med13 Cyclin C Degradation Following Cellular Stress, Ayesha Gurnani, Brittany Friedson, Katrina Cooper
Rowan-Virtua Research Day
The Cdk8 Kinase Module is a dissociable regulator of cellular stress response genes, with degradation of its components Med13 and cyclin C eventually determining cell fate decisions such as engaging cell survival or cell death mechanisms. We aimed to explore the roles of ubiquitin in degradation of the Cdk8 Kinase Module following nitrogen starvation, with respect to the potential involvement of deubiquitinating enzyme Doa4, lysine linkage at position K63, and E2 ubiquitin conjugating enzymes Ubc4 and Ubc5. We utilized Western blot analysis to observe nitrogen starvation-induced degradation of Med13-HA in wild-type, doa4 mutant, and K63R yeast strains; degradation of cyclin …
Nicotinamide Riboside And Beta-Hydroxybutyrate Activate Parallel Pathways For C. Elegans Lifespan Extension, Mckenzie Peters
Nicotinamide Riboside And Beta-Hydroxybutyrate Activate Parallel Pathways For C. Elegans Lifespan Extension, Mckenzie Peters
Undergraduate Honors Theses
Supplementation with nicotinamide riboside (NR), a form of vitamin B3 and a precursor of nicotinamide adenine dinucleotide (NAD+) extends lifespan in the nematode C. elegans and delays aging-related pathologies in mammals. During aging, levels of NAD+ decline causing metabolic dysfunction and oxidative damage. Studies in C. elegans found that when NR was administered during larval development it induced the mitochondrial unfolded protein response (UPRmt), which is frequently associated with lifespan extension. Both calorie restriction (CR) and ketogenic diets (KD) have been shown to extend lifespan, in part through increasing NAD+ and through increasing levels …
Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao
Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao
Graduate School of Biomedical Sciences Theses and Dissertations
Dysregulated hyperinflammatory host immune response to underlying bacterial infections is a characteristic of sepsis. In sepsis, bacteria often trigger abnormal hyperinflammatory responses which can cause multiple organ failure and if sustained can lead to an immunosuppressive phase where the host is susceptible to secondary infections caused by opportunistic bacteria like Pseudomonas aeruginosa (P. aeruginosa). In our studies, we used a 2-hit model of cecal ligation and puncture (CLP) followed by P. aeruginosa secondary lung infection to investigate cellular and molecular mechanisms in the beneficial action of resolvin D2 (RvD2). Resolvins of the D-series are a group of fatty acids known …
Role Of Pseudomonas Aeruginosa Exoenzymes S, T, And Y In The Modulation Of Intrinsic Apoptosis In Pulmonary Microvascular Endothelial Cells, Andrea M. Vavrinek
Role Of Pseudomonas Aeruginosa Exoenzymes S, T, And Y In The Modulation Of Intrinsic Apoptosis In Pulmonary Microvascular Endothelial Cells, Andrea M. Vavrinek
Honors Theses
P. aeruginosa is the most common cause of ventilator-associated pneumonia in ICU patients. P. aeruginosa uses a type III secretion system to inject exoenzymes S, T, U, and Y into host cells, exhibiting unique effects. Pulmonary microvascular endothelial cells (PMVECs) are used to evaluate cellular changes caused by exoenzymes. ExoY infection of PMVECs leads to cell rounding but does not lead to cell death, unlike ExoS/T. The current study evaluated the exoenzyme-induced modulation of intrinsic apoptosis in endothelial cells. Strain PAK, producing ExoS, T, and Y, was compared to isogenic strains expressing either S, SY, T, TY, Y, or none …
Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing
Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing
Dissertations & Theses (Open Access)
Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …
Transferring Organelles Into Native Neurons: A Disease-Modifying Therapy For Neurodegenerative Disorders, Lohiny Balendran
Transferring Organelles Into Native Neurons: A Disease-Modifying Therapy For Neurodegenerative Disorders, Lohiny Balendran
Electronic Thesis and Dissertation Repository
Currently, there are no disease-modifying therapies to counter the progression of neurodegenerative diseases that are associated with mitochondrial dysfunction in the early stages. In this study, we have used a novel strategy of cell fusion to transfer mitochondria from one cell to another using fusogens (syncytin 1 and syncytin 2). Syncytins are placental proteins encoded by endogenous retroviral envelope genes that promote cellular fusion. In this study, we have proposed that donor cells engineered to stably express syncytin when cocultured with recipient cells will allow fusion and facilitate the transfer of mitochondria into recipient cells. Syncytin-mediated systems revealed about 16.6-18.5% …
Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh
Undergraduate Research Posters
Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …
Characterizing The Effects Of Antiandrogens And Senolytics To Enhance The Therapeutic Response To Castration-Resistant Prostate Cancer, Justin M. Silverman
Characterizing The Effects Of Antiandrogens And Senolytics To Enhance The Therapeutic Response To Castration-Resistant Prostate Cancer, Justin M. Silverman
Theses and Dissertations
Prostate cancer is the most frequently diagnosed cancer in males and the second most common cause of cancer deaths. Androgen deprivation therapy, whether through surgical or chemical castration, is the mainstay for treatment of advanced prostate cancer; however, despite an initial response, most patients eventually develop a progressive PSA rise, and castration- sensitive prostate cancer gives rise to castration-resistant prostate cancer. The standard of care therapy includes the antiandrogens such as enzalutamide and abiraterone acetate as well as the microtubule poison, docetaxel, and various immunotherapies; however, while prostate cancer research is progressing, there continues to be a compelling need for …
Risk-Factor Induced Changes In The Breast Microenvironment Facilitate Inflammatory Breast Cancer Progression And Lymphovascular Invasion, Wintana Balema, Wintana Balema
Risk-Factor Induced Changes In The Breast Microenvironment Facilitate Inflammatory Breast Cancer Progression And Lymphovascular Invasion, Wintana Balema, Wintana Balema
Dissertations & Theses (Open Access)
Inflammatory breast cancer (IBC) is a rapidly progressing, rare and highly lethal form of breast cancer. IBC is a clinical diagnosis, requiring >1/3 involvement on the affected breast and/or skin by erythema, and disease onset of < 6 months. The clinical symptoms of IBC vary in severity and presentation, these include redness, warmth, skin thickening and bruised or pink/purple discoloration appearance and skin changes such as peau d’orange. These skin symptoms are not attributed to inflammation, rather IBC is characterized by florid lymphovascular tumor emboli clogging dermal lymphatics. This leads to “classic” symptoms of breast swelling and skin edema or discoloration. To date, unique genomic drivers which differentiate IBC from non-IBC invasive breast cancers have not been identified highlighting a role for the microenvironment. Several epidemiological studies have unveiled subtype-specific risk factors associated with IBC that are known to alter the microenvironment. Obesity is an established risk factor for all subtypes of IBC. Never-breastfeeding increases risk for developing the most aggressive, triple-negative IBC. Further, never breastfeeding is associated with later clinical stage and worse outcomes. We worked to model these overlapping risk factors to understand microenvironment changes that may lead to the lymphatic change’s indicative of IBC.
First, we investigated the association of a “classic” triad of clinical IBC signs with overall survival among patients to demonstrate the most overt clinical findings of lymphatic involvement were impacting prognosis. We evaluated a triad of IBC signs, including swollen involved breast, nipple change, and diffuse skin change, using breast medical photographs from patients enrolled on a prospective IBC registry. We reported that the …
Constructing An In Vitro 3d Model Of The Human Placenta, Michael Zheng
Constructing An In Vitro 3d Model Of The Human Placenta, Michael Zheng
Undergraduate Student Research Internships Conference
The placenta is critical for nurturing fetal growth and development, with dysregulated placentation associated with adverse pregnancy outcomes. The main fetal and maternal placental components consist of trophoblasts and modified endometrial stromal cells known as decidual cells, respectively. Since investigating in vivo placentas in humans through non-invasive methods is challenging, comprehensive in vitro placental models are needed for in-depth studies. However, in vitro 3D placental models that adequately represent and combine fetal and maternal components have been lacking. In this study, we achieved valuable progress in developing an in vitro 3D placental model inclusive of fetal and maternal constituents. We …
Mistranslating Trnas Alter The Heat Shock Activation By Hsf1, Rebecca Dib
Mistranslating Trnas Alter The Heat Shock Activation By Hsf1, Rebecca Dib
Undergraduate Student Research Internships Conference
Translation, or the production of protein from an mRNA blueprint, is among the most fundamental processes to life as we know it. tRNAs are essential to accurate translation, as they decode the codons of mRNA and recruit corresponding amino acids. Variant tRNAs with anticodon mutations can decrease translational fidelity by recruiting the incorrect amino acid, an aberrant process known as mistranslation. When proteins are produced with incorrect amino acid sequences, they may misfold. The heat shock response functions to alleviate cellular stress caused by misfolded proteins, either by refolding or targeting misfolded proteins for degradation. Hsf1 acts as a transcriptional …
Subtype-Selective Positive Modulation Of KCa2.3 Channels Increases Cilia Length, Young-Woo Nam, Rajasekharreddy Pala, Naglaa Salem El-Sayed, Denisse Laren-Henriquez, Farideh Amirrad, Grace Yang, Mohammad Asikur Rahman, Razan Orfali, Myles Downey, Keykavous Parang, Surya M. Nauli, Miao Zhang
Subtype-Selective Positive Modulation Of KCa2.3 Channels Increases Cilia Length, Young-Woo Nam, Rajasekharreddy Pala, Naglaa Salem El-Sayed, Denisse Laren-Henriquez, Farideh Amirrad, Grace Yang, Mohammad Asikur Rahman, Razan Orfali, Myles Downey, Keykavous Parang, Surya M. Nauli, Miao Zhang
Pharmacy Faculty Articles and Research
Small-conductance Ca2+-activated potassium (KCa2.x) channels are gated exclusively by intracellular Ca2+. The activation of KCa2.3 channels induces hyperpolarization, which augments Ca2+ signaling in endothelial cells. Cilia are specialized Ca2+ signaling compartments. Here, we identified compound 4 that potentiates human KCa2.3 channels selectively. The subtype selectivity of compound 4 for human KCa2.3 over rat KCa2.2a channels relies on an isoleucine residue in the HA/HB helices. Positive modulation of KCa2.3 channels by compound 4 increased flow-induced Ca2+ signaling and cilia length, while negative …
Dual Mechanisms Implemented By Lin-28 For Positive Regulation Of Hbl-1 Are Necessary For Proper Development Of Distinct Tissues In Caenorhabditis Elegans, Madeleine Minutillo
Dual Mechanisms Implemented By Lin-28 For Positive Regulation Of Hbl-1 Are Necessary For Proper Development Of Distinct Tissues In Caenorhabditis Elegans, Madeleine Minutillo
Graduate School of Biomedical Sciences Theses and Dissertations
In Caenorhabditis elegans, the heterochronic pathway is comprised of a hierarchy of genes that control the proper timing of developmental events. hbl-1 (Hunchback Like-1) encodes an Ikaros family zinc-finger transcription factor that promotes the L2 stage cell fate events of the hypodermis. The downregulation ofhbl-1 is a crucial step for the transition from the L2 to the L3 stage. There are two known processes through which negative regulation of hbl-1 occurs: suppression of hbl-1 expression by 3 let-7 miRNAs through the hbl-1 3’UTR and inhibition of HBL-1 activity by LIN-46. The mechanisms by which hbl-1 is positively regulated have not …
A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser
A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser
Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship
Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this …
Primary Cilia Of The Cardiac Neural Crest & Hedgehog-Mediated Mechanisms Of Congenital Heart Disease, Lindsey A. Fitzsimons
Primary Cilia Of The Cardiac Neural Crest & Hedgehog-Mediated Mechanisms Of Congenital Heart Disease, Lindsey A. Fitzsimons
Electronic Theses and Dissertations
Elimination of primary cilia in cardiac neural crest cell (CNCC) progenitors is hypothesized to cause a variety of congenital heart defects (CHDs), including atrioventricular septal defects, and malformations of the developing cardiac outflow tract. We present an in vivo model of CHD resulting from the conditional elimination of primary cilia from CNCC using multiple, Wnt1:Cre-loxP, neural crest-specific systems, targeting two distinctive, but critical, primary cilia structural genes: Intraflagellar transport protein 88 (Ift88) or kinesin family member 3A (Kif3a). CNCC loss of primary cilia leads to widespread CHD, where homozygous mutant embryos (MUT) display a variety of outflow tract malformations, septation …
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
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 …
Cdk8 Kinase Module Modifies Expression Of Specific Translation-Related Proteins Before And After Stress, Brittany Friedson, Katrina Cooper
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 …
A Patient-Derived Ipsc Model To Study Glutamate Deficiency By Shank-3 Mutation In Autism Spectrum Disorder, Tiffany Berry, Courtney Caccia
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
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 …