ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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- All Subjects: Biology
- Creators: Liebig, Jürgen
- Creators: Chen, Qiang
treatments, and neo-antigens are the targets of immune system in cancer patients who
respond to the treatments. The cancer vaccine field is focused on using neo-antigens from
unique point mutations of genomic sequence in the cancer patient for making
personalized cancer vaccines. However, we choose a different path to find frameshift
neo-antigens at the mRNA level and develop broadly effective cancer vaccines based on
frameshift antigens.
In this dissertation, I have summarized and characterized all the potential frameshift
antigens from microsatellite regions in human, dog and mouse. A list of frameshift
antigens was validated by PCR in tumor samples and the mutation rate was calculated for
one candidate – SEC62. I develop a method to screen the antibody response against
frameshift antigens in human and dog cancer patients by using frameshift peptide arrays.
Frameshift antigens selected by positive antibody response in cancer patients or by MHC
predictions show protection in different mouse tumor models. A dog version of the
cancer vaccine based on frameshift antigens was developed and tested in a small safety
trial. The results demonstrate that the vaccine is safe and it can induce strong B and T cell
immune responses. Further, I built the human exon junction frameshift database which
includes all possible frameshift antigens from mis-splicing events in exon junctions, and I
develop a method to find potential frameshift antigens from large cancer
immunosignature dataset with these databases. In addition, I test the idea of ‘early cancer
diagnosis, early treatment’ in a transgenic mouse cancer model. The results show that
ii
early treatment gives significantly better protection than late treatment and the correct
time point for treatment is crucial to give the best clinical benefit. A model for early
treatment is developed with these results.
Frameshift neo-antigens from microsatellite regions and mis-splicing events are
abundant at mRNA level and they are better antigens than neo-antigens from point
mutations in the genomic sequences of cancer patients in terms of high immunogenicity,
low probability to cause autoimmune diseases and low cost to develop a broadly effective
vaccine. This dissertation demonstrates the feasibility of using frameshift antigens for
cancer vaccine development.
This work investigates mechanisms that can extend the spatial reach of fertility signaling and reproductive regulation in three polydomous ant species. In Novomessor cockerelli, the presence of larvae but not eggs is shown to inhibit worker reproduction. Then, in Camponotus floridanus, 3-methylheptacosane found on the queen cuticle and queen-laid eggs is verified as a releaser pheromone sufficient to disrupt normally occurring aggressive behavior toward foreign workers. Finally, the volatile and cuticular hydrocarbon pheromones present on the cuticle of Oecophylla smaragdina queens are shown to release strong attraction response by workers; when coupled with previous work, this result suggests that these chemicals may underly both the formation of a worker retinue around the queen as well as egg-located mechanisms of reproductive regulation in distant satellite nests. Whereas most previous studies have focused on the short-range role of hydrocarbons on the cuticle of the queen, these studies demonstrate that eusocial insects may employ longer range regulatory mechanisms. Both queen volatiles and distributed brood can extend the range of queen fertility signaling, and the use of larvae for fertility signaling suggest that feeding itself may be a non-chemical mechanism for reproductive regulation. Although trail laying in mass-recruiting ants is often used as an example of complex communication, reproductive regulation in ants may be a similarly complex example of insect communication, especially in the case of large, polydomous ant colonies.