Digital Commons Network^™

Investigating Propargyl-Linked Antifolates In Inhibiting Bacterial And Fungal Dihydrofolate Reductase, Joshua Andrade

Honors Scholar Theses

Antimicrobial agents have been invaluable in reducing illness and death associated with bacterial infection. However, over time, bacteria have evolved resistance to all major drug classes as a result of selective pressure. The advancement of new drug compounds is therefore vital. The Anderson-Wright Lab has focused on developing potent and selective inhibitors of dihydrofolate reductase (DHFR), an enzyme key in cell proliferation and survival, in several pathogenic species. The lab has found that a set of compounds, known as propargyl-linked antifolates, are DHFR inhibitors that are both biologically effective and have strong pharmacokinetic properties.

The efficacy of novel propargyl-linked antifolates …

Targeting Grp78 In Cancer With Nucleic Acid Bioconjugates, Pradeepkumar L. Patel

Seton Hall University Dissertations and Theses (ETDs)

Nucleic acid bioconjugates have gained widespread use in medicinal chemistry research programs aimed at fighting human malignancies such as cancer, diabetes, genetic and infectious diseases. Their popularity stems from their ability to accelerate the drug development process by conjugating chemical functionality that may improve the pharmacology of a bioactive nucleoside. Moreover, this strategy has been proven to be effective with small molecule nucleoside analogs and those derived from lengthy oligonucleotide sequences. Considering these fruitful applications, my research and this thesis aims to explore the synthesis, characterization and therapeutic potential of novel classes of nucleic acid bioconjugates.

These are based on, …

Simple, Label-Free And Non-Instrumented Analyte Quantitation By Flow Distance Measurement In Microfluidic Devices, Debolina Chatterjee

Theses and Dissertations

Rapid determination of the concentrations of molecules related to diseases can provide timely information for treatment options. However, most biomarker quantitation methods require costly and complex equipment. On the other hand, point-of-care systems have less complex instrumentation needs than laboratory-based equipment, but often provide less information; for example, biomarker presence or absence instead of concentration. A complete analysis setup addressing key limitations of both laboratory-based and portable systems is highly desirable. I developed microfluidic devices with visual inspection readout of a target’s concentration from microliter volumes of solution flowed into a microchannel. Microchannels are formed within polydimethylsiloxane (PDMS), and the …

The Microtubule-Associated Protein, Eb1, Links Aim2 Inflammasomes With Autophagy-Dependent Secretion, Li-Jie Wang, Hsin-Yi Huang, Meng-Pin Huang, Willisa Liou, Ya-Ting Chang, Chih-Ching Wu, David M. Ojcius, Yu-Sun Chang

All Dugoni School of Dentistry Faculty Articles

Inflammasomes are multi-protein complexes that regulate chronic inflammation-associated diseases by inducing interleukin-1 β (IL-1β) secretion. Numerous components involved in inflammasome activation have been identified, but the mechanisms of inflammasome-mediated IL-1β secretion have not yet been fully explored. Here, we demonstrate that end-binding protein 1 (EB1), which is required for activation of AIM2 inflammasome complex, links the AIM2 inflammasome to autophagy-dependent secretion. Imaging studies revealed that AIM2 inflammasomes colocalize with microtubule organizing centers and autophagosomes. Biochemical analyses showed that poly(dA-dT)-activated AIM2 inflammasomes induce autophagy and IL-1β secretion in an LC3-dependent fashion. Furthermore, depletion of EB1 decreases autophagic shedding and intracellular trafficking. …

Antiviral Responses In Mouse Embryonic Stem Cells: Differential Development Of Cellular Mechanisms In Type I Interferon Production And Response, Ruoxing Wang

Dissertations

Embryonic stem cells (ESCs) have been recognized as a promising cell source for regenerative medicine. Intensive research over the past decade has led to the possibility that ESC-derived cells will be used for the treatment of human diseases. However, increasing evidence indicates that ESC-derived cells generated by the current differentiation methods are not fully functional. It is recently recognized that ESC-derived cells lack innate immunity to a wide range of infectious agents and inflammatory cytokines. When used in patients, ESC-derived cells would be placed in wounded sites that are exposed to various pathogens and inflammatory cytokines; therefore, their viability and …

Primary Amoebic Meningoencephalitis Caused By Naegleria Fowleri: An Old Enemy Presenting New Challenges, Ruqaiyyah Siddiqui, Naveed Ahmed Khan

Department of Biological & Biomedical Sciences

First discovered in 1899, Naegleria fowleri is a protist pathogen, known to infect the central nervous system and produce primary amoebic meningoencephalitis. The most distressing aspect is that the fatality rate has remained more than 95%, despite our advances in antimicrobial chemotherapy and supportive care. Although rare worldwide, most cases have been reported in the United States, Australia, and Europe (France). A large number of cases in developing countries go unnoticed. In particular, religious, recreational, and cultural practices such as ritual ablution and/or purifications, Ayurveda, and the use of neti pots for nasal irrigation can contribute to this devastating infection. …

Evaluation Of Eight Live Attenuated Vaccine Candidates For Protection Against Challenge With Virulent Mycobacterium Avium Subspecies Paratuberclosis In Mice, John Bannantine, Jamie L. Everman, Sasha J. J.Rose, Lmar Babrak, Robab Katani, Raul G. Barletta, Adel M. Talaat, Yrjö J. Gröhn, Yung-Fu Chang, Vivek Kapur, Luiz E. Bermudez

School of Veterinary and Biomedical Sciences: Faculty Publications

Johne's disease is caused by Mycobacterium avium subsp. paratuberculosis (MAP), which results in serious economic losses worldwide in farmed livestock such as cattle, sheep, and goats. To control this disease, an effective vaccine with minimal adverse effects is needed. In order to identify a live vaccine for Johne's disease, we evaluated eight attenuated mutant strains of MAP using a C57BL/6 mouse model. The persistaence of the vaccine candidates was measured at 6, 12, and 18 weeks post vaccination. Only strains 320, 321, and 329 colonized both the liver and spleens up until the 12-week time point. The remaining five mutants …

Investigation Into The Control Of Melittin Secondary Structure And Antimicrobial Activity, Zachary B. Molinets

Open Access Theses

Antimicrobial resistance has been an exponentially growing problem since the discovery of antibiotics. Antibiotics have been misused for many years and this misuse has grown into a real problem for the medical community. While there are countless safeguards to prevent infection by a resistant strain of bacteria, there are still many plagued by it and must be treated with sometimes dangerous antibiotics. Melittin, along with many other peptides, contain potent antimicrobial properties, but are also toxic toward enthrocytes. The control of the secondary structure of peptides provides the key to adjusting their activity.

Key Residues Of Human Cytoplasmic Protein Tyrosine Phosphatase-A And -B For Substrate Binding And Specificity, Byunghyun Park

Open Access Theses

Reversible tyrosine phosphorylation plays an important role in signaling pathways that are essential for regulating cellular growth, differentiation and metabolism. Moreover, several human diseases such as diabetes, obesity and cancers are associated with the deregulation of protein tyrosine phosphatases (PTPs). Several studies provide evidence that PTPs not only contribute to cellular differentiation, but over-expression of these molecules also leads to transformation of non-transfomed cells as well. Based on these results, designing specific PTP inhibitors may ultimately function as potential therapeutic agents to treat various diseases including cancer, diabetes, and autoimmune diseases. EphA2 is a receptor tyrosine kinase which is hypo-phosphorylated …

Identification Of Cd24 As A Cancer Stem Cell Marker In Human Nasopharyngeal Carcinoma, Chun-Hung Yang, Hui-Ling Wang, Yi-Sheng Lin, K. P. Shravan Kumar, Hung-Chi Lin, Chih-Jung Chang, Chia-Chen Lu, Tsung-Teng Huang, Jan Martel, David M. Ojcius, Yu-Sun Chang, John Ding-E. Young, Hsin-Chih Lai

All Dugoni School of Dentistry Faculty Articles

Cancer stem cells (CSCs) represent a unique sub-population of tumor cells with the ability to initiate tumor growth and sustain self-renewal. Although CSC biomarkers have been described for various tumors, only a few markers have been identified for nasopharyngeal carcinoma (NPC). In this study, we show that CD24⁺ cells isolated from human NPC cell lines express stem cell genes (Sox2, Oct4, Nanog, Bmi-1, and Rex-1), and show activation of the Wnt/β-catenin signaling pathway. CD24⁺ cells possess typical CSC characteristics that include enhanced cell proliferation, increased colony and sphere formation, maintenance of cell differentiation potential in prolonged …

Novel Cell Cycle Proteins In Apicomplexan Parasites, Carrie Butler

USF Tampa Graduate Theses and Dissertations

Apicomplexans are responsible for major human diseases such as toxoplasmosis caused by Toxoplasma gondii (T. gondii) and the deadliest form of malaria caused by Plasmodium falciparum (P. falciparum). The genomes of these pathogens are now sequenced ushering in a new era of drug development. A major hurdle to exploiting this genome resource is that a large number of the encoded genes are "hypotheticals" and have yet to be characterized. Hypothetical proteins comprise roughly half of the predicted gene complement of T. gondii and P. falciparum and represent the largest class of uniquely functioning proteins in these parasites.

Following the idea …

Characterizing The Response Of Multidrug-Resistant Klebsiella Pneumoniae Species To The Application Of A Phage Cocktail, Steven Liu

Symposium

Project Summary: The application of bacteriophages to treat bacterial infections is known as phage therapy, which takes advantage of bacteriophage’s natural ability to infect and lyse bacterial hosts. Phages have been shaped by billions of years of evolution to be highly specialized deliverers of bactericidal agents to the cytoplasm of their target bacteria. Ever since discovery of bacteriophages in 1915, phage therapy was recognized as a potentially powerful tool for eliminating bacterial infections. The effectiveness of phage therapy can be increased by creating a mixture of multiple phages to target a wider variety of bacterial strains. Furthermore, phage therapy has …

Oxidation Of Cellular Amino Acid Pools Leads To Cytotoxic Mistranslation Of The Genetic Code, Tammy J. Bullwinkle, Noah M. Reynolds, Medha Raina, Adil Moghal, Eleftheria Matsa, Andrei Rajkovic, Huseyin Kayadibi, Farbod Fazlollahi, Christopher Ryan, Nathaniel Howitz, Kym F. Faull, Beth A. Lazazzera, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Aminoacyl-tRNA synthetases use a variety of mechanisms to ensure fidelity of the genetic code and ultimately select the correct amino acids to be used in protein synthesis. The physiological necessity of these quality control mechanisms in different environments remains unclear, as the cost vs benefit of accurate protein synthesis is difficult to predict. We show that in Escherichia coli, a non-coded amino acid produced through oxidative damage is a significant threat to the accuracy of protein synthesis and must be cleared by phenylalanine-tRNA synthetase in order to prevent cellular toxicity caused by mis-synthesized proteins. These findings demonstrate how stress …

Conformationally Stabilized Hiv Envelope Immunogens, Peter Kwong, John Mascola, Gary Nabel, Richard Wyatt, Barna Dey, Ling Xu, Tongqing Zhou, Joseph Sodroski, Wen Yuan, Shi-Hua Xiang

School of Veterinary and Biomedical Sciences: Faculty Publications

Isolated immunogens including a HIV-1 gp120 polypeptide or immunogenic fragment thereof stabilized in a CD4 bound confirmation by crosslinked cysteines, and methods of their use are disclosed. The immunogens are useful, for example, for generating an immune response to HIV-1 gp120 in a Subject.

Basal Nf-Κb Controls Il-7 Responsiveness Of Quiescent Naïve T Cells, Michelle L. Miller, Luqiu Chen, Ping Zhou, Xindong Liu, Monica Michelotti, Nicole Tramontini Gunn, Sarah E. Powers, Xiaoping Zhu, Cesar Evaristo, Maria-Luisa Alegre, Luciana L. Molinero

Biology Department Faculty Articles

T cells are essential for immune defenses against pathogens, such that viability of naïve T cells before antigen encounter is critical to preserve a polyclonal repertoire and prevent immunodeficiencies. The viability of naïve T cells before antigen recognition is ensured by IL-7, which drives expression of the prosurvival factor Bcl-2. Quiescent naïve T cells have low basal activity of the transcription factor NF-κB, which was assumed to have no functional consequences. In contrast to this postulate, our data show that basal nuclear NF-κB activity plays an important role in the transcription of IL-7 receptor α-subunit (CD127), enabling responsiveness of naïve …

Reclaiming The Efficacy Of Β-Lactam–Β-Lactamase Inhibitor Combinations: Avibactam Restores The Susceptibility Of Cmy-2-Producing Escherichia Coli To Ceftazidime, Krisztina M. Papp-Wallace, Marisa L. Winkler, Julian A. Gatta, Magdalena A. Taracila, Sujatha Chilakala, Yan Xu, J. Kristie Johnson, Robert A. Bonomo

Chemistry Faculty Publications

CMY-2 is a plasmid-encoded Ambler class C cephalosporinase that is widely disseminated in Enterobacteriaceae and is responsible for expanded-spectrum cephalosporin resistance. As a result of resistance to both ceftazidime and β-lactamase inhibitors in strains carrying blaCMY, novel β-lactam–β-lactamase inhibitor combinations are sought to combat this significant threat to β-lactam therapy. Avibactam is a bridged diazabicyclo [3.2.1]octanone non-β-lactam β-lactamase inhibitor in clinical development that reversibly inactivates serine β-lactamases. To define the spectrum of activity of ceftazidime-avibactam, we tested the susceptibilities of Escherichia coli clinical isolates that carry blaCMY-2 or blaCMY-69 and investigated the inactivation kinetics of CMY-2. Our analysis showed that …

Phthalates And Phthalate Alternatives: Effects On Proliferative And Estrogenic Target Genes In Ishikawa Cells, Ranjani Sundar '15, Ping Yin, Serdar E. Bulun

Student Publications & Research

Phthalates are used as plasticizers in many of the products found in medical, household, and industrial applications. Much research has not been completed on the effects of these phthalates as potential endocrine disrupting chemicals (EDCs). As these chemicals are ingested, the mechanism by which they affect the reproductive system is largely unknown. The purpose of this study was to observe how 2 phthalates, Di-n-butyl phthalate (DBP) and Diisononyl phthalate (DINP), and 2 phthalate alternatives, Dioctyl terephthalate (DOTP) and BHT (butylated hydroxytoluene)affect uterine cells in comparison to a vehicle treatment and 17β-Estradiol treatment. Changes in expression of mRNA were observed using …

The Effect Of Small Molecule 390 On Cxcr4 Receptors, Selam B. Zenebe-Gete '14, Shruti R. Topudurti '14, Shum Andrew, Richard J. Miller

Student Publications & Research

CXCR4 is the chemokine receptor which aids in chemotaxis of stem cells, such as those in the bone marrow or the brain. SDF-1 is the natural ligand for the CXCR4 receptor. Similarities between novel molecule 390 synthesized by the Miller Lab and SDF-1 make this novel small molecule a possible agonist of the CXCR4 receptor. To determine whether 390 is an agonist to the CXCR4 receptor, we transfected cells with CXCR4 and exposed them to no agonist [vehicle control], SDF-1, or varying concentrations of our agonist drug. Next, we took calcium images using the dye fura-2, which indicates changes in …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

The Role Of Stress-Activated Protein Kinases In Parasites, Tamara Kreiss

Theses, Dissertations and Culminating Projects

Lymphatic filariasis and leishmaniasis are neglected tropical diseases that are caused by nematode and protozoal parasites. These diseases cause disfiguration, leaving their host socially marked, and in some cases cause more severe disease that can lead to death. These infections, which tend to persist for long periods of time, also lead to bacterial and fungal co-infections, which further exacerbate the disease. Currently there are insufficient treatment options. Current therapies are often too expensive, have toxicity associated with them and are subjected to growing resistance amongst parasite populations. In this thesis I investigated two potential drug targets. The first, is the …

Synthesis And Characterization Of Co(Ii) And Cu(Ii) Pyrophosphate Coordination Complexes For Treatment Of Pathogenic Agents., Leann Jade Miles

Renée Crown University Honors Thesis Projects - All

Candidiasis, the yeast infection of the mouth, genitals, and blood can be fatal in individuals who are immunocompromised. In humans, Candidiasis is most commonly caused by the yeast, Candida albicans (C. albicans), but can also be caused by other Candida species .^[1]

C. albicans demonstrates marked resistance towards Cu(II) but more sensitivity towards Co(II) compounds, especially in mutants that lack the CaCRP1 and CaCUP1 gene that encodes for the copper-transporting P-type ATPase and Metallothionein proteins, respectively.^[2] Here, I will describe the effects of Co(II) and Cu(II) metal based complexes that incorporate a bridging pyrophosphate …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Trail-R1 Is A Negative Regulator Of Pro-Inflammatory Responses And Modulates Long-Term Sequelae Resulting From Chlamydia Trachomatis Infections In Humans, Mufadhal Al-Kuhlani, James Rothchild, Sukumar Pal, Luis M. De La Maza, Sander Ouberg, Servaas A. Morré, Deborah Dean, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

The immune system eliminates Chlamydia trachomatis infection through inflammation. However, uncontrolled inflammation can enhance pathology. In mice, TNF-related apoptosis-inducing ligand receptor (TRAIL-R), known for its effects on apoptosis, also regulates inflammation. In humans, the four homologues of TRAIL-R had never been investigated for effects on inflammation. Here, we examined whether TRAIL-R regulates inflammation during chlamydial infection. We examined TRAIL-R1 single nucleotide polymorphisms (SNPs) in an Ecuadorian cohort with and without C. trachomatis infections. There was a highly significant association for the TRAIL+626 homozygous mutant GG for infection vs no infection in this population. To confirm the results observed in the …

Cd8Α Dendritic Cells Drive Establishment Of Hsv-1 Latency, Kevin R. Mott, Sariah J. Allen, Mandana Zandian, Bindu Konda, Behrooz G. Sharifi, Clinton Jones, Steven L. Wechsler, Terrence Town, Homayon Ghiasi

School of Veterinary and Biomedical Sciences: Faculty Publications

It is generally accepted that CD8 T cells play the key role to maintain HSV-1 latency in trigeminal ganglia of ocularly infected mice. Yet, comparably little is known about the role of innate immunity in establishment of viral latency. In the current study, we investigated whether CD8α DCs impact HSV-1 latency by examining latency in the trigeminal ganglia (TG) of wildtype (WT) C57BL/6 versus CD8α^‒/‒ (lack functional CD8 T cells and CD8α⁺ DCs), CD8β^‒/‒ (have functional CD8α⁺ T cells and CD8α⁺ DCs), and β2m^‒/‒ (lack functional CD8 T cells but have CD8α^{+ …}

Overexpression Of Thioredoxin Binding Protein (Tbp-2) Increases Oxidation Sensitivity And Apoptosis In Human Lens Epithelial Cells, Yibo Yu, Kuiyi Xing, Rilwan Badamas, Charles A. Kuszynski, Hongli Wuand, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Thioredoxin (Trx) is an important redox regulator with cytosolic Trx1 and mitochondrial Trx2 isozymes. Trx has multi-physiological functions in cells and its bioavailability is negatively controlled through active site binding to a specific thioredoxin binding protein (TBP-2). This paper describes the delicate balance between TBP-2 and Trx, and the effect of overexpression of TBP-2 in the human lens epithelial cells. Cells overexpressing TBP-2 (TBP-2 OE) showed a 7- fold increase of TBP-2, and a nearly 40% suppression of Trx activity but no change in Trx expression. The TBP-2 OE cells grew slower and their population decreased to 30% by day …

Pathogenic Mechanisms And Signaling Pathways In Plasmodium Falciparum, Jennifer L. Sedillo

USF Tampa Graduate Theses and Dissertations

Plasmodium falciparum is a human intracellular parasite that is the causative agent of a deadly form of malaria. This species alone is responsible for 200 million cases of malaria annually resulting in over 1 million deaths worldwide. The excessive mortality due to P. falciparum infection is due to its ability to cause severe pathogenesis through hyperparasitemia and cytoadherence defined as the ability of infected red blood cells to adhere to host vasculature. Cytoadherence is mediated through the export of parasite proteins to the surface of the infected red blood cell (RBC). Exported proteins have been identified but the pathway for …

Molecular Evidence For Vector Implication Of Onchocerca Lupi In Los Angeles County, Ca, Shanna June Bolcen

USF Tampa Graduate Theses and Dissertations

Onchocerca is a genus of roundworm most commonly associated with the human infection onchocerciasis, or river blindness. While typically a zoonotic infection of ungulate populations, canine cases (Onchocerca lupi) have been identified in the United States and Greece. In 2012, Los Angeles County, Veterinary Public Health Program identified 3 cases of Onchocerca spp. infections in domestic canines. Samples from the ensuing blackfly collections were sent to the Global Health Infectious Disease Research Unnasch Laboratory for parasite isolation and vector species identification. Species-specific primers were designed and optimized for O. lupi using a non- specific cytochrome oxidase (COI) gene target (689bp) …

Combined Metal-Enhanced Fluorescence-Surface Acoustic Wave (Mef-Saw) Biosensor, Samuel Morrill

USF Tampa Graduate Theses and Dissertations

Immunofluorescence assays are capable of both detecting the amount of a protein and the location of the protein within a cell or tissue section. Unfortunately, the traditional technique is not capable of detecting concentrations on the nanoscale. Also, the technique suffers from non-specific attachment, which can cause false-positives, as well as photobleaching when detecting lower concentrations is attempted. There is also a time constraint problem since the technique can take from many hours to a few days in some cases.

In this work, metal-enhanced fluorescence (MEF) is used to lower the detection limit and reduce photobleaching. Unfortunately, MEF also increases …

Evaluation Of Novel Oral Vaccine Candidates And Validation Of A Caprine Model Of Johne’S Disease, Murray E. Hines Ii, Sue E. Turnquist, Marcia R.S. Ilha, Sreekumari Rajeev, Arthur L. Jones, Lisa Whittington, John P. Bannantine, Raul G. Barletta, Yrjö T. Gröhn, Robab Katani, Adel M. Talaat, Lingling Li, Vivek Kapur

School of Veterinary and Biomedical Sciences: Faculty Publications

Johne’s disease (JD) caused by Mycobacterium avium subspecies paratuberculosis (MAP) is a major threat to the dairy industry and possibly some cases of Crohn’s disease in humans. A MAP vaccine that reduced of clinical disease and/or reduced fecal shedding would aid in the control of JD. The objectives of this study were (1) to evaluate the efficacy of 5 attenuated strains of MAP as vaccine candidates compared to a commercial control vaccine using the protocol proposed by the Johne’s Disease Integrated Program (JDIP) Animal Model Standardization Committee (AMSC), and (2) to validate the AMSC Johne’s disease go at challenge model. …

Molecular Pap Biomarkers For Cervical Cancer Risk Assessment In Thinprep® Clinical Specimens, Jennifer Taylor

Graduate School of Biomedical Sciences Theses and Dissertations

Approximately 500,000 patients are diagnosed with cervical cancer worldwide each year, thus making it the second most common cause of cancer-related deaths in women. Persistent high-risk human papillomavirus (HR-HPV) infections induce cervical dysplasia by increasing the expression of two viral oncogenes, E6 and E7. Utilization of the Papanicolaous smear test (Pap test) has contributed to a decrease in morbidity and mortality of cervical cancer; however, subjective analysis of cell morphology with a limited amount of cells has led to a substantial rate of false positive and false negative diagnoses. A more objective and sensitive diagnostic tool for the detection of …