Biology Commons^™

Position-Scanning Peptide Libraries As Particle Immunogens For Improving Cd8+ T-Cell Responses, Michael C. Vega

Faculty Articles, Papers, and Other Scholarship

Short peptides reflecting major histocompatibility complex (MHC) class I (MHC-I) epitopes frequently lack sufficient immunogenicity to induce robust antigen (Ag)-specific CD8⁺ T cell responses. In the current work, it is demonstrated that position-scanning peptide libraries themselves can serve as improved immunogens, inducing Ag-specific CD8⁺ T cells with greater frequency and function than the wild-type epitope. The approach involves displaying the entire position-scanning library onto immunogenic nanoliposomes. Each library contains the MHC-I epitope with a single randomized position. When a recently identified MHC-I epitope in the glycoprotein gp70 envelope protein of murine leukemia virus (MuLV) is assessed, only one …

Detailed Evaluation Of Cancer Sequencing Pipelines In Different Microenvironments And Heterogeneity Levels, Batuhan Kisakol, Şahi̇n Sarihan, Mehmet Ari̇f Ergün, Mehmet Baysan

Turkish Journal of Biology

The importance of next generation sequencing (NGS) rises in cancer research as accessing this key technology becomes easier for researchers. The sequence data created by NGS technologies must be processed by various bioinformatics algorithms within a pipeline in order to convert raw data to meaningful information. Mapping and variant calling are the two main steps of these analysis pipelines, and many algorithms are available for these steps. Therefore, detailed benchmarking of these algorithms in different scenarios is crucial for the efficient utilization of sequencing technologies. In this study, we compared the performance of twelve pipelines (three mapping and four variant …

Toward Uncharted Territory Of Cellular Heterogeneity: Advances And Applications Of Single-Cell Rna-Seq, Brandon Lieberman, Meena Kusi, Chia Nung Hung, Chih Wei Chou, Ning He, Yen Yi Ho, Josephine A. Taverna, Tim H.M. Huang, Chun Liang Chen

Faculty Publications

Among single-cell analysis technologies, single-cell RNA-seq (scRNA-seq) has been one of the front runners in technical inventions. Since its induction, scRNA-seq has been well received and undergone many fast-paced technical improvements in cDNA synthesis and amplification, processing and alignment of next generation sequencing reads, differentially expressed gene calling, cell clustering, subpopulation identification, and developmental trajectory prediction. scRNA-seq has been exponentially applied to study global transcriptional profiles in all cell types in humans and animal models, healthy or with diseases, including cancer. Accumulative novel subtypes and rare subpopulations have been discovered as potential underlying mechanisms of stochasticity, differentiation, proliferation, tumorigenesis, and …

Investigating The Antitumor Effects Of A Dsrna-Nanoparticle Complex In An In Vitro Ovarian Cancer Model, Aaron Lewis

Theses and Dissertations (Comprehensive)

An estimated 1 in 70 women will be diagnosed with ovarian cancer in their lifetime. Despite advanced detection and treatment methods, it remains a silent killer with an expected survival rate of 50%. A developing method in cancer treatment is the use of compounds that stimulate the immune system to aid in the body's fight against the disease. This project focused on the use of the potent immune stimulant double-stranded RNA (dsRNA), commercially available as polyinosinic:polycytidylic acid, poly(I:C), to induce cytotoxicity in two ovarian cancer cell lines; SKOV-3 and OVCAR-3. Some challenges exist with the delivery of dsRNA due to …

Validating The Methods And Assays Necessary For Establishing An Effective In Vitro Lung Cancer Transformation Model, Crystal Turner

Theses and Dissertations

In my research, I developed tools and performed assays to study the in vitro transformation of immortalized lung epithelial cells by oncogenic KRAS^G12V. I delivered the KRAS by transfection and lentiviral transduction, and after confirming the cells expressed KRAS, I evaluated transformation using several experimental approaches including monitoring of EMT markers and various types of growth assays. I also conducted preliminary experiments that quantified sphingolipid alterations in the cells that had markers indicative of having gone through EMT. The goal of these experiments was to assess whether sphingolipids are altered in cells that are transformed in vitro by …

Immunohistochemical Localization Of Prolactin Receptor (Prlr) To Hodgkin's And Reed-Sternberg Cells Of Hodgkin's Lymphoma, Rajendra Gharbaran, Onyekwere Onwumere, Naomi Codrington, Latchman Somenarian, Stephen Redenti

Publications and Research

Prolactin receptor (PRLR), a type-1 cytokine receptor, is overexpressed in a number of cancer types. It has attracted much attention for putative pro-oncogenic roles, which however, remains controversial in some malignancies. In this study, we reported the localization of PRLR to the Hodgkin's and Reed-Sternberg (HRS) cells of Hodgkin's lymphoma (HL), a neoplasm of predominantly B cell origin. Immunohistochemistry performed on 5-μm thick FFPE sections revealed expression of PRLR in HRS cells. Cellular immunofluorescence experiments showed that the HL-derived cell lines, Hs445, KMH2 and L428 overexpressed PRLR. The PRLR immunofluorescent signal was depleted after treating the cell lines with 10 …

Luteolin Induces Cytotoxicity In Mix Cellularity Classical Hodgkin's Lymphoma Via Caspase Activated-Cell Death, Rajendra Gharbaran, Enyuan Shang, Onyekwere Onwumere, Naomi Codrington, Evangelina Dankwa Sarpong, Stephen M. Redenti

Publications and Research

Background/aim: We investigated the effects of luteolin (LUT) on classical Hodgkin's lymphoma (cHL), since such studies in malignant lymphomas are lacking.

Materials and methods: Effect of LUT on cell growth was assessed with water-soluble tetrazolium 1 (WST-1) cell proliferation assay and automated hemocytometry on trypan blue-exclusion assay. Cell death was investigated with acridine orange/ethidium bromide live-dead assay, propidium iodide (PI) flow cytometry, and Annexin-V-PI microscopy. Caspase activation was studied using CellEvent Caspase-3/7 Green detection reagent. High resolution immunofluorescence microscopy was used to detect cleaved-PARP-1.

Results: LUT induced a dose-dependent decrease in the growth of KMH2 and L428 cells, cellular models …

Mechanisms Of Cross-Presentation By Cdc1s, Derek James Theisen

Arts & Sciences Graduate Student Theses and Dissertations

Classical dendritic cells (cDCs) are specialized antigen presenting cells that can be divided into distinct subsets based on the types of pathogens they respond to and the type of immune response they generate. The cDC1 subset is specialized in priming CD8 T cell responses through the process of cross-presentation. During cross-presentation, exogenous protein antigens are taken up by cDC1 and presented on MHCI molecules, allowing for the priming of CD8 T cells during conditions when DCs themselves are not directly infected. The ability to cross-present in vivo is unique to cDC1, and is essential for anti-viral responses and rejection of …

Genetic Analysis Of Pi3k And Mtor Inhibition In U87mg Glioblastoma Cell Line, Carl G. Litif

Theses and Dissertations

NVP-BEZ235 is a Glioblastoma Multiform chemotherapeutic dual PI3K/mTOR pathway inhibitor created in 2008 and has since been proven experimentally to induce pluripotentcy in oncological cell populations. The inhibition of PI3K and mTOR has shown to coerce phenotypes associated with stem cell markers, most notably OCT4. It is necessary to understand the genetic composure of how PI3K/mTOR inhibited tumor cells are bypassing the canonical pathway for proliferation and growth and utilizing other parallel sources for tumor invasion into other neural regions. Taking a genetic approach with RNA-sequencing allowed us to gain insight into how glioblastoma interact with cytoskeleton factors MAPK4 and …

Effects Of Aurora Kinase C Expression On Retina Pigmented Epithelial Cell Migration, Proliferation, And Anchorage Independent Growth, Justin Bejar

Seton Hall University Dissertations and Theses (ETDs)

Cancer is a common and deadly disease in the United States with 1,806,590 new cancer cases in 2019 and 606,520 cancer deaths projected in 2020. These deaths are primarily due to the uncontrolled cell proliferation and migratory nature of the disease. Many cancer cells express genes normally restricted to meiotic cells. For example, Aurora Kinase C (AURKC) is known to regulate chromosome segregation in meiotic cells yet it is expressed in many different types of cancer, such as breast, prostate, colorectal, liver, cervical, thyroid, and testicular cancers. As a means to study the function of AURKC, an …

Multi-Omics Integration For Gene Fusion Discovery And Somatic Mutation Haplotyping In Cancer, Steven Mason Foltz

Arts & Sciences Graduate Student Theses and Dissertations

Cancer is a disease caused by changes to the genome and dysregulation of gene expression. Among many types of mutations, including point mutations, small insertions and deletions, large scale structural variants, and copy number changes, gene fusions are another category of genomic and transcriptomic alteration that can lead to cancer and which can serve as therapeutic targets. We studied gene fusion events using data from The Cancer Genome Atlas, including over 9,000 patients from 33 cancer types, finding patterns of gene fusion events and dysregulation of gene expression within and across cancer types. With data from the CoMMpass study (Multiple …

The Small Heat Shock Protein Αb-Crystallin Is Critical To Cell Survival In Response To The Phytochemical Withaferin A In Cisplatin-Resistant Ovarian Cancer Cells, Melissa Carmichael

Honors Program Theses and Projects

Withaferin A (WA), the active-phytochemical of the medicinal plant Withania somnifera, promotes apoptosis in cancer cells. Although its mechanism remains unclear, WA has been shown to upregulate heat shock proteins (Hsps) which protect against diverse cellular insults. The small Hsps, αB-Crystallin and Hsp27, confer resistance to chemotherapy in several cancer cell lines, however, the role of WA on αB-Crystallin and Hsp27 expression in drug resistance remains unknown. Since the majority of ovarian tumors eventually recur in a drug-resistant form leaving patients few treatment options, the goal of this study is to explore the molecular mechanism induced by WA in a …

Novel Cyanoximates As An Alternative In Cancer Chemotherapy, Kafayat Aderonke Yusuf

Graduate Theses/Dissertations

Chemotherapy is one of the most effective treatment plans for several cancer types. The recurrent side effects derived from chemotherapy agents have warranted the search for novel chemical compounds with better efficacy and minimal side effects. In line with this idea, I investigated effects of a group of newly synthesized metal based chemical compounds called cyanoximates on HeLa human cancer cells. Cyanoximates used were Pt(DECO)₂, Pt(MCO)₂, and Pd(DECO)₂ along with the chemotherapy drug cisplatin as a positive control. I found that the metal cyanoximates reduced cell viability via apoptosis, and that Pt(DECO)₂ was most …

Investigating The Localization Of Foxo Transcription Factors In Glioblastoma, Leetoria Hinojosa

Theses and Dissertations

The Phosphatidylinositol 3 Kinase (PI3K) pathway is an essential intracellular signaling pathway that regulates cellular growth, survival, and fate. Canonically, the activation of this pathway removes forkhead box subfamily O transcription factors (FOXO -1, -3, and -4) from the nucleus. However, in cancer cells such as glioblastoma multiforme, FOXO factors are at least in part nuclear despite the activation of the PI3K pathway. Previous research indicated that FOXO3 localization was not affected when the pathway was inhibited in breast cancer cells, which challenged the conventional paradigms for FOXO factor regulation. Therefore, we were interested in investigating the nuclear localization of …

Synthesis Of An Arylidene Pyrazolone And Its Effects On Glioblastoma Cancer Cells, Joanna Deonarine

Honors Theses

The purpose of this research is to develop a new technique to synthesize a heterocyclic arylidene compound using fruit puree catalysis and investigate its anti-cancer activity on glioblastoma cancer cells. Recently, there has been interest in heterocycles due to their anticancer properties and they have been used in almost two-thirds of the novel molecular anticancer agents. Varying fruit purees were used to synthesize a novel hybrid arylidene pyrazolone from 3-methyl-1-phenyl-5-pyrazolone and 4-dimethylaminobenzaldehyde by modifying methodology developed by Dr. Murray. This arylidene pyrazolone was then tested for its anticancer activity on glioblastoma brain cancer cells using Dr. Smith’s 12-well cell viability …

Assay Development For Isolation And Characterization Of Anticancer Properties Of Marine Fungi, Kyra Ricci

Honors Theses

Metabolites from fungi have potential use in the drug discovery process and have been used in the past to develop therapeutic agents for human use. Initial characterization of potential therapeutic properties of fungi is thus an important first step in identifying novel therapeutic compounds. In the present study, marine fungi were isolated from Myrtle Beach and assayed for anticancer properties using the soft agar colony formation assay in a 3D in vitro cellular environment. Many species were isolated from environmental samples, displaying unique morphologies and growth patterns. To optimize the soft agar assay in a six-well cell culture plate for …

The Relationship Between The Cervical Microbiome And Cervical Cancer Risk In Sub-Saharan Africa, Cameron G. Klein

School of Biological Sciences: Dissertations, Theses, and Student Research

Despite ongoing efforts, sub-Saharan Africa faces a higher cervical cancer burden than anywhere else in the world. Besides HPV infection, definitive factors of cervical cancer are still unclear. Dysbiosis of the cervicovaginal microbiota, particularly involving sexually transmitted infections, is associated with increased cervical cancer risk. Notably, HIV infection, which is prevalent in sub-Saharan Africa, greatly increases risk of cervicovaginal dysbiosis and cervical cancer. To better understand and address cervical cancer in sub-Saharan Africa, a better understanding of the regional cervicovaginal microbiome is required. In this study, I establish the relationship between cervical cancer, HPV, HIV, cervicovaginal infections, and the cervicovaginal …

Is Pnc-27 And Pnc-28 The Best Way To Cure Cancer?, Miriam Silberstein

The Science Journal of the Lander College of Arts and Sciences

Immunotherapeutic agents have been researched for many decades as an alternative treatment for cancer. Current research demonstrates that immunotherapy is safer than radiotherapy or chemotherapy. This is attributed to immunotherapy’s mechanism of utilizing the body’s own defense system, as opposed to absorbing harmful chemicals. Two forms of immunotherapy that have been effective in curing cancer without the added danger of chemical toxicity are PNC-27 and PNC-28. These peptides were created by a supercomputer at SUNY Downstate Medical Center in New York in 2000. PNC-27 and PNC-28 work with the MDM2 -P53 tumor suppressor complex. It acts as a competitive inhibitor …

Which Hypothesis Best Explains The Development Of Cancer?, Ariel M. Mayer

The Science Journal of the Lander College of Arts and Sciences

There are three theories of cancer development analyzed in this review. The first theory is the immunological theory, which states that cancer is a result of the immune system failing to detect a cancerous cell in which results in uncontrolled cell growth. The second theory is the somatic mutation theory, which states that genetic mutations are a direct cause cancer. The third theory is the stem cell theory which states that cancer results from an uncontrolled stem cell. The difference in each theory helps guide a clinician’s judgment in how to treat cancer. If a clinician believes in the immunological …

A Look At Gene Control: Tracking The Ccnd1 Gene, Bryan Anders

Mahurin Honors College Capstone Experience/Thesis Projects

Cancer occurs when the cell does not properly control its own cell cycle. It then replicates in an out of control fashion leading to the death of various organs and then the demise of the organism as a whole. As it seems to have always been a problem for cell-based life, certain safeguards against cancer have been evolved over time. One such method comes in the form of prevention via cyclin proteins, which are encoded from cyclin genes. The gene that is the focus of this research is the CCND1, or cyclin D1, gene that controls the progression through various …

Ototoxicity Of Cisplatin, Pyriplatin, And Phenathriplatin In The Auditory Hybridoma Cell Line, Hei-Oc1, Alexandra Johnston

Mahurin Honors College Capstone Experience/Thesis Projects

Cisplatin is an anti-cancer drug which is effective against several cancers, but also causes harmful side-effects, including ototoxicity and hearing loss. While cisplatin is a bifunctional compound that forms coordinate covalent bonds with both strands of DNA, recently investigated monofunctional platinum(II) compounds bind to only one DNA strand, and may activate different cell-death mechanisms. As several monofunctional platinum(II) compounds have anti-cancer properties, but could target different cell-death pathways, they could potentially have different and reduced side-effects. In this study, the HEI-OC1 auditory hybridoma cell line was used to investigate the ototoxicity of cisplatin and two monofunctional platinum(II) compounds, phenanthriplatin and …

Identification Of A Novel Single Amino Acid Substitution (V666g) Of Jak1 From A Patient With Acute Lymphoblastic Leukemia Impairs Jak3 Mediated Il-2 Signaling, Alice Hernandez Grant

Open Access Theses & Dissertations

The Janus kinase (JAK) family, notably JAK1, JAK2 and JAK3 are recognized as oncogenic drivers in high risk Acute Lymphoblastic Leukemia (ALL). The bulk of activating JAK mutations are thought to occur within functional hot-spots across Janus Homology (JH) domains. The most frequently mutated regions is the JH2 pseudo-kinase, which provides a negative regulatory role to the adjacent catalytically active JH1 kinase domain. Despite the prevalence of JAK activating mutations and a need for new therapeutic inhibitors, there is a lack of understanding in the allosteric regulation of JAK kinases. Here we sought to identify mutations involved in driving ALL …

The Effect Of Natural Extracts On Border Cell And Centripetal Cell Migration In The Developing Drosophila Melanogaster Egg Chamber, Kirandeep Kaur

Undergraduate Honors Thesis Collection

Cancer is one of the leading causes of death in the world. Although targeted therapies that specifically inhibit pathways that are activated in cancer cells are becoming more common, often times the specific cancer-causing pathways are not known, or a treatment targeting that pathway has not been developed. In the absence of a targeted therapy, most common cancer treatments target proliferating cells, which can cause many unwanted adverse side effects. Therefore, researchers are testing whether natural extracts or dietary supplements could reduce the growth or metastasis of cancer cells without as many negative side effects. This study uses the Drosophila …

Bioenergetic Modulation Of Retinal Progenitor Cell Glycolysis To Drive Invasion For Photoreceptor Replacement, Jei Espinal

Theses and Dissertations

Given the limited regenerative capacity of the mammalian retina, cell-replacement strategies are necessary. To replace photoreceptors lost to disease or trauma and restore visual function, laboratories throughout the world are researching photoreceptors replacement strategies using subretinal transplantation of retinal progenitor cells (RPCs). A major obstacle to the advancement of photoreceptor cell-replacement strategies includes low rates of invasion and integration of transplanted cells into the host retina. Currently, there is a limited understanding of how RPC glycolysis may facilitate invasion. To further understand RPC glycolysis-driven invasion, the current investigation involved the bioenergetic modulation RPCs for glycolysis analysis and invasion modeling. The …

Sphingolipids In Cancer Health Disparities And As Prospective Targets For Cancer Therapy, April E. Boyd

Theses and Dissertations

Lung cancer is the deadliest cancer both in the United States and worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. However, lung cancer disparities are not shared equally across racial groups, with large differences between African American and Caucasian populations. Advances in research have revealed roles of lipid mediators in cancer biology and disease progression, but sphingolipid alterations in tissues should be explored further. To address this, using mass spectrometry (MS), extensive sphingolipidomic characterization of NSCLC tumors and adjacent uninvolved tissues from African American and Caucasian patients were performed. This study revealed that NSCLC …

Oncogenic And Tumor Suppressor Function Of Meis And Associated Factors, Bi̇rkan Gi̇rgi̇n, Medi̇ne Karadağ Alpaslan, Fati̇h Kocabaş

Turkish Journal of Biology

MEIS proteins are historically associated with tumorigenesis, metastasis, and invasion in cancer. MEIS and associated PBXHOX proteins may act as tumor suppressors or oncogenes in different cellular settings. Their expressions tend to be misregulated in various cancers. Bioinformatic analyses have suggested their upregulation in leukemia/lymphoma, thymoma, pancreas, glioma, and glioblastoma, and downregulation in cervical, uterine, rectum, and colon cancers. However, every cancer type includes, at least, a subtype with high MEIS expression. In addition, studies have highlighted that MEIS proteins and associated factors may function as diagnostic or therapeutic biomarkers for various diseases. Herein, MEIS proteins and associated factors in …

Mitochondria Imaging And Targeted Cancer Treatment, Tinghan Zhao

Dissertations

Mitochondria are essential organelles as the site of respiration in eukaryotic cells and are involved in many crucial functions in cell life. Dysfunction of mitochondrial metabolism and irregular morphology have been frequently found in human cancers. The capability of imaging mitochondria as well as regulating their microenvironment is important both scientifically and clinically. Mitochondria penetrating peptides (MPPs), certain peptides that are composed of cationic and hydrophobic amino acids, are good candidates for mitochondria targeting. Herein, a novel MPP, D-argine-phenylalanine-D-argine-phenylalanine-D-argine-phenylalanine-NH₂ (rFrFrF), is conjugated with a rhodamine-based fluorescent chromophore (TAMRA). The TAMRA-rFrFrF probe exhibits advantageous properties for long-term mitochondria tracking of …

Cul3 Regulates Cyclin E1 Protein Abundance Via A Degron Located Within The N-Terminal Region Of Cyclin E, Brittney Marie Davidge, Katia De Oliveira Rebola, Larry N. Agbor, Curt D. Sigmund, Jeffrey D. Singer

Biology Faculty Publications and Presentations

mammalian cells. Increased levels of cyclin E are found in some cancers. Additionally, proteolytic removal of the cyclin E N-terminus occurs in some cancers and is associated with increased cyclin E–Cdk2 activity and poor clinical prognosis. Cyclin E levels are tightly regulated and controlled in part through ubiquitin-mediated degradation initiated by one of two E3 ligases, Cul1 and Cul3. Cul1 ubiquitylates phosphorylated cyclin E, but the mechanism through which Cul3 ubiquitylates cyclin E is poorly understood. In experiments to ascertain how Cul3 mediates cyclin E destruction, we identified a degron on cyclin E that Cul3 targets for ubiquitylation. Recognition of …

Evidence For P53-Mediated Induction Of Wrap53a In Response To Dna Damage, Anne Shelton Hucks

Theses and Dissertations

p53 is a powerful tumor suppressor mutated in approximately half of all cancers. Its mRNA is stabilized post-transcriptionally via complementary base pairing with the transcript of its antisense gene, WRAP53α; without this interaction, p53 protein cannot accumulate enough to carry out its many functions related to apoptosis, cell cycle arrest, and DNA damage repair. Previous studies have shown that WRAP53α is induced in response to DNA damage. The purpose of this study was to determine which transcription factors might be responsible for this induction. After identifying three putative p53 binding sites on the WRAP53α promoter, we used chromatin immunoprecipitation …

Hyperinsulinemia, Cancer And Maqui Berry: The Promise Of Nutritional Supplementation, Brett Deters, Mir Saleem

Biology Faculty Articles

Nutritional supplementation has long been studied as a possible treatment alternative or as an adjunct to the standard treatments for common ailments and diseases. According to the latest research, the Chilean maqui berry, Aristotelia chilensis, has been shown to reduce postprandial insulin levels by as much as fifty percent. The berry, which has been shown to be as effective as metformin at increasing insulin sensitivity and controlling blood glucose levels, follows a simple mechanism of action that involves the inhibition of sodium dependent glucose transporters in the small intestine, slowing the rate at which sugars enter the bloodstream and thereby …