Matching Items (492)
Description
Cancer is one of the most serious global diseases. We have focused on cancer immunoprevention. My thesis projects include developing a prophylactic primary and metastatic cancer vaccines, early cancer detection and investigation of genes involved in tumor development. These studies were focused on frame-shift (FS) antigens. The FS antigens are generated by genomic mutations or abnormal RNA processing, which cause a portion of a normal protein to be translated out of frame. The concept of the prophylactic cancer vaccine is to develop a general cancer vaccine that could prevent healthy people from developing different types of cancer. We have discovered a set of cancer specific FS antigens. One of the FS candidates, structural maintenance of chromosomes protein 1A (SMC1A) FS, could start to accumulate at early stages of tumor and be specifically exposed to the immune system by tumor cells. Prophylactic immunization with SMC1A-FS could significantly inhibit primary tumor development in different murine tumor models and also has the potential to inhibit tumor metastasis. The SMC1A-FS transcript was detected in the plasma of the 4T1/BALB/c mouse tumor model. The tumor size was correlated with the transcript ratio of the SMC1A-FS verses the WT in plasma, which could be measured by regular RT-PCR. This unique cancer biomarker has a practical potential for a large population cancer screen, as well as clinical tumor monitoring. With a set of mimotope peptides, antibodies against SMC1A-FS peptide were detected in different cancer patients, including breast cancer, pancreas cancer and lung cancer with a 53.8%, 56.5% and 12.5% positive rate respectively. This suggested that the FS antibody could be a biomarker for early cancer detection. The characterization of SMC1A suggested that: First, the deficiency of the SMC1A is common in different tumors and able to promote tumor initiation and development; second, the FS truncated protein may have nucleolus function in normal cells. Mis-control of this protein may promote tumor development. In summary, we developed a systematic general cancer prevention strategy through the variety immunological and molecular methods. The results gathered suggest the SMC1A-FS may be useful for the detection and prevention of cancer.
ContributorsShen, Luhui (Author) / Johnston, Stephen Albert (Thesis advisor) / Chang, Yung (Committee member) / Miller, Laurence (Committee member) / Sykes, Kathryn (Committee member) / Jacobs, Bertram (Committee member) / Arizona State University (Publisher)
Created2012
Description
The advent of new high throughput technology allows for increasingly detailed characterization of the immune system in healthy, disease, and age states. The immune system is composed of two main branches: the innate and adaptive immune system, though the border between these two states is appearing less distinct. The adaptive immune system is further split into two main categories: humoral and cellular immunity. The humoral immune response produces antibodies against specific targets, and these antibodies can be used to learn about disease and normal states. In this document, I use antibodies to characterize the immune system in two ways: 1. I determine the Antibody Status (AbStat) from the data collected from applying sera to an array of non-natural sequence peptides, and demonstrate that this AbStat measure can distinguish between disease, normal, and aged samples as well as produce a single AbStat number for each sample; 2. I search for antigens for use in a cancer vaccine, and this search results in several candidates as well as a new hypothesis. Antibodies provide us with a powerful tool for characterizing the immune system, and this natural tool combined with emerging technologies allows us to learn more about healthy and disease states.
ContributorsWhittemore, Kurt (Author) / Sykes, Kathryn (Thesis advisor) / Johnston, Stephen A. (Committee member) / Jacobs, Bertram (Committee member) / Stafford, Phillip (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2014
Description
Peptide microarrays are to proteomics as sequencing is to genomics. As microarrays become more content-rich, higher resolution proteomic studies will parallel deep sequencing of nucleic acids. Antigen-antibody interactions can be studied at a much higher resolution using microarrays than was possible only a decade ago. My dissertation focuses on testing the feasibility of using either the Immunosignature platform, based on non-natural peptide sequences, or a pathogen peptide microarray, which uses bioinformatically-selected peptides from pathogens for creating sensitive diagnostics. Both diagnostic applications use relatively little serum from infected individuals, but each approaches diagnosis of disease differently. The first project compares pathogen epitope peptide (life-space) and non-natural (random-space) peptide microarrays while using them for the early detection of Coccidioidomycosis (Valley Fever). The second project uses NIAID category A, B and C priority pathogen epitope peptides in a multiplexed microarray platform to assess the feasibility of using epitope peptides to simultaneously diagnose multiple exposures using a single assay. Cross-reactivity is a consistent feature of several antigen-antibody based immunodiagnostics. This work utilizes microarray optimization and bioinformatic approaches to distill the underlying disease specific antibody signature pattern. Circumventing inherent cross-reactivity observed in antibody binding to peptides was crucial to achieve the goal of this work to accurately distinguishing multiple exposures simultaneously.
ContributorsNavalkar, Krupa Arun (Author) / Johnston, Stephen A. (Thesis advisor) / Stafford, Phillip (Thesis advisor) / Sykes, Kathryn (Committee member) / Jacobs, Bertram (Committee member) / Arizona State University (Publisher)
Created2014
Description
African Swine Fever (ASF), endemic in many African countries, is now spreading to other continents. Though ASF is capable of incurring serious economic losses in affected countries, no vaccine exists to provide immunity to animals. Disease control relies largely on rapid diagnosis and the implementation of movement restrictions and strict eradication programs. Developing a scalable, accurate and low cost diagnostic for ASF will be of great help for the current situation. CIM's 10K random peptide microarray is a new high-throughput platform that allows systematic investigations of immune responses associated with disease and shows promise as a diagnostic tool. In this study, this new technology was applied to characterize the immune responses of ASF virus (ASFV) infections and immunizations. Six sets of sera from ASFV antigen immunized pigs, 6 sera from infected pigs and 20 sera samples from unexposed pigs were tested and analyzed statistically. Results show that both ASFV antigen immunized pigs and ASFV viral infected pigs can be distinguished from unexposed pigs. Since it appears that immune responses to other viral infections are also distinguishable on this platform, it holds the potential of being useful in developing a new ASF diagnostic. The ability of this platform to identify specific ASFV antibody epitopes was also explored. A subtle motif was found to be shared among a set of peptides displaying the highest reactivity for an antigen specific antibody. However, this motif does not seem to match with any antibody epitopes predicted by a linear antibody epitope prediction.
ContributorsXiao, Liang (Author) / Sykes, Kathryn (Thesis advisor) / Zhao, Zhan-Gong (Committee member) / Stafford, Phillip (Committee member) / Arizona State University (Publisher)
Created2011
Description
We propose a novel solution to prevent cancer by developing a prophylactic cancer. Several sources of antigens for cancer vaccines have been published. Among these, antigens that contain a frame-shift (FS) peptide or viral peptide are quite attractive for a variety of reasons. FS sequences, from either mistake in RNA processing or in genomic DNA, may lead to generation of neo-peptides that are foreign to the immune system. Viral peptides presumably would originate from exogenous but integrated viral nucleic acid sequences. Both are non-self, therefore lessen concerns about development of autoimmunity. I have developed a bioinformatical approach to identify these aberrant transcripts in the cancer transcriptome. Their suitability for use in a vaccine is evaluated by establishing their frequencies and predicting possible epitopes along with their population coverage according to the prevalence of major histocompatibility complex (MHC) types. Viral transcripts and transcripts with FS mutations from gene fusion, insertion/deletion at coding microsatellite DNA, and alternative splicing were identified in NCBI Expressed Sequence Tag (EST) database. 48 FS chimeric transcripts were validated in 50 breast cell lines and 68 primary breast tumor samples with their frequencies from 4% to 98% by RT-PCR and sequencing confirmation. These 48 FS peptides, if translated and presented, could be used to protect more than 90% of the population in Northern America based on the prediction of epitopes derived from them. Furthermore, we synthesized 150 peptides that correspond to FS and viral peptides that we predicted would exist in tumor patients and we tested over 200 different cancer patient sera. We found a number of serological reactive peptide sequences in cancer patients that had little to no reactivity in healthy controls; strong support for the strength of our bioinformatic approach. This study describes a process used to identify aberrant transcripts that lead to a new source of antigens that can be tested and used in a prophylactic cancer vaccine. The vast amount of transcriptome data of various cancers from the Cancer Genome Atlas (TCGA) project will enhance our ability to further select better cancer antigen candidates.
ContributorsLee, HoJoon (Author) / Johnston, Stephen A. (Thesis advisor) / Kumar, Sudhir (Committee member) / Miller, Laurence (Committee member) / Stafford, Phillip (Committee member) / Sykes, Kathryn (Committee member) / Arizona State University (Publisher)
Created2012
Description
Breast microcalcifications are a potential indicator of cancerous tumors. Current visualization methods are either uncomfortable or impractical. Impedance measurement studies have been performed, but not in a clinical setting due to a low sensitivity and specificity. We are hoping to overcome this challenge with the development of a highly accurate impedance probe on a biopsy needle. With this technique, microcalcifications and the surrounding tissue could be differentiated in an efficient and comfortable manner than current techniques for biopsy procedures. We have developed and tested a functioning prototype for a biopsy needle using bioimpedance sensors to detect microcalcifications in the human body. In the final prototype a waveform generator sends a sin wave at a relatively low frequency(<1KHz) into the pre-amplifier, which both stabilizes and amplifies the signal. A modified howland bridge is then used to achieve a steady AC current through the electrodes. The voltage difference across the electrodes is then used to calculate the impedance being experienced between the electrodes. In our testing, the microcalcifications we are looking for have a noticeably higher impedance than the surrounding breast tissue, this spike in impedance is used to signal the presence of the calcifications, which are then sampled for examination by radiology.
ContributorsWen, Robert Bobby (Co-author) / Grula, Adam (Co-author) / Vergara, Marvin (Co-author) / Ramkumar, Shreya (Co-author) / Kozicki, Michael (Thesis director) / Ranjani, Kumaran (Committee member) / School of Molecular Sciences (Contributor) / Electrical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Breastfeeding has been shown by a number of studies to have numerous benefits on both the mother and the infant. Major health organizations such as the World Health Organization (WHO), now agree that breastfeeding should be encouraged and supported in all countries. But like many things, the wheels of the law are slow to catch up with scientific evident. Although breastfeeding is supported, working women do not have the option of breastfeeding without consequences. For example, in 2003, Kirstie Marshall, a then member of parliament in Australia was ejected from the lower house chamber on February 23, for breastfeeding her baby [3]. According to standing order 30 at the time, "Unless by order of the House, no Member of this House shall presume to bring any stranger into any part of the House appropriated to the Members of this House while the House, or a Committee of the whole House, is sitting" [3]. The rules did not specify the age of strangers, so the then 11-day-old baby, Charlotte Louise and her mother were shown the exit door of parliament. She had to choose between being present at times of major discussions or leaving the house to breastfeed her child, she chose to leave. More recent statistics show that developed nations like the US and Australia which also have high rates of women employment had low rates of breastfeeding. This might mean that workplace policies do not favor breastfeeding or expressing milk at work. Fortunately, laws have since been introduced in both the United States and Australia that support breastfeeding at the workplace. The next step would be to access how these laws affect breastfeeding statistics and how variation between these two countries like the paid parental leave in Australia (which is not present in all US states) would affect these numbers.
ContributorsSakala, Lydia (Author) / Alison, Alison (Thesis director) / Reddy, Swapna (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Ketone bodies are produced in the liver from the acetyl CoA derived from fatty acids that cannot enter the Krebs cycle. This is a sub-analysis of a larger study which had numerous outcome markers. This analysis focuses on the relationship between ketone blood levels and cognition. The study looked at the relationship between Time Restricted Feeding (TRF), a method of intermittent fasting. TRF is something that can be easily adapted into an individual’s lifestyle and has been shown to have multiple advantages. This 8-week study began with 23 enrolled participants, but due to COVID-19 only 11 participants could be tested for cognition and blood ketone levels after week 4. All participants had similar ranges of weight, height, age, BMI, hip, and waist measurements at baseline. Moreover, these demographic variables were not related to ketone levels or cognition. The data indicate that ketone bodies increased in participants practicing TRF and that the increase in ketone bodies in the blood, specifically β-hydroxybutyrate was strongly correlated to increased cognitive function. This is consistent with theories that elevated ketone levels allowed for early hunter-gather communities and other mammals to survive prolonged periods of nutrient deprivation while keeping high cognitive function.
ContributorsTaha, Basel Mahmoud (Author) / Johnston, Carol (Thesis director) / Karen, Sweazea (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
The purpose of this thesis experiment was to design and create an Acoustically Active Cannula (AAC), which is furnished by a piezoelectric crystal placed at its tip that produces an acoustic navigation signal. I tested the functionality of the cannula in vitro and demonstrated its navigational abilities in vivo in anesthetized pigs. This experiment was based upon ultrasound science and technology, and thus some practical experience with conventional (B-mode) and Doppler ultrasound was achieved as well. The results of bench and experimental animal studies indicated proper functionality of the AAC for identification and spatial navigation of its tip with color Doppler ultrasound imaging.
ContributorsShamsa, Kayvan (Author) / Tyler, William (Thesis director) / Belohlavek, Marek (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The academic study of eSports, or professional competition through the medium of video games, has tended to focus on players' motivations to play and watch eSports as well as marketing concerns of huge eSports corporations. Instead of utilizing marketing or psychology to analyze this phenomenon, I investigate three areas of focus in accordance with available literature: the fans and their characteristics, the design of the game itself, and the relationship between fans and the game's developer. This investigation was conducted by first examining existing literature surrounding eSports fans, then collecting public domain data such as Reddit posts, forum posts, and YouTube videos, and last by studying interviews with developers and players. With this thesis, I apply a fan studies approach to eSports by creating a series of indicators based in each of the three focus areas which can be utilized as a systematic method of evaluating an eSport's popularity and growth.
ContributorsHilliker, Noah Henry (Author) / Ingram-Waters, Mary (Thesis director) / Schmidt, Peter (Committee member) / Anderson, Sky (Committee member) / School of Molecular Sciences (Contributor) / W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05