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- Creators: Kusumi, Kenro
- Creators: Dean, W.P. Carey School of Business
Description
Well-established model systems exist in four out of the seven major classes of vertebrates. These include the mouse, chicken, frog and zebrafish. Noticeably missing from this list is a reptilian model organism for comparative studies between the vertebrates and for studies of biological processes unique to reptiles. To help fill in this gap the green anole lizard, Anolis carolinensis, is being adapted as a model organism. Despite the recent release of the complete genomic sequence of the A. carolinensis, the lizard lacks some resources to aid researchers in their studies. Particularly, the lack of transcriptomic resources for lizard has made it difficult to identify genes complete with alternative splice forms and untranslated regions (UTRs). As part of this work the genome annotation for A. carolinensis was improved through next generation sequencing and assembly of the transcriptomes from 14 different adult and embryonic tissues. This revised annotation of the lizard will improve comparative studies between vertebrates, as well as studies within A. carolinensis itself, by providing more accurate gene models, which provide the bases for molecular studies. To demonstrate the utility of the improved annotations and reptilian model organism, the developmental process of somitogenesis in the lizard was analyzed and compared with other vertebrates. This study identified several key features both divergent and convergent between the vertebrates, which was not previously known before analysis of a reptilian model organism. The improved genome annotations have also allowed for molecular studies of tail regeneration in the lizard. With the annotation of 3' UTR sequences and next generation sequencing, it is now possible to do expressional studies of miRNA and predict their mRNA target transcripts at genomic scale. Through next generation small RNA sequencing and subsequent analysis, several differentially expressed miRNAs were identified in the regenerating tail, suggesting miRNA may play a key role in regulating this process in lizards. Through miRNA target prediction several key biological pathways were identified as potentially under the regulation of miRNAs during tail regeneration. In total, this work has both helped advance A. carolinensis as model system and displayed the utility of a reptilian model system.
ContributorsEckalbar, Walter L (Author) / Kusumi, Kenro (Thesis advisor) / Huentelman, Matthew (Committee member) / Rawls, Jeffery (Committee member) / Wilson-Rawls, Norma (Committee member) / Arizona State University (Publisher)
Created2012
Description
Induced pluripotent stem cells (iPSCs) are an intriguing approach for neurological disease modeling, because neural lineage-specific cell types that retain the donors' complex genetics can be established in vitro. The statistical power of these iPSC-based models, however, is dependent on accurate diagnoses of the somatic cell donors; unfortunately, many neurodegenerative diseases are commonly misdiagnosed in live human subjects. Postmortem histopathological examination of a donor's brain, combined with premortem clinical criteria, is often the most robust approach to correctly classify an individual as a disease-specific case or unaffected control. We describe the establishment of primary dermal fibroblasts cells lines from 28 autopsy donors. These fibroblasts were used to examine the proliferative effects of establishment protocol, tissue amount, biopsy site, and donor age. As proof-of-principle, iPSCs were generated from fibroblasts from a 75-year-old male, whole body donor, defined as an unaffected neurological control by both clinical and histopathological criteria. To our knowledge, this is the first study describing autopsy donor-derived somatic cells being used for iPSC generation and subsequent neural differentiation. This unique approach also enables us to compare iPSC-derived cell cultures to endogenous tissues from the same donor. We utilized RNA sequencing (RNA-Seq) to evaluate the transcriptional progression of in vitro-differentiated neural cells (over a timecourse of 0, 35, 70, 105 and 140 days), and compared this with donor-identical temporal lobe tissue. We observed in vitro progression towards the reference brain tissue, supported by (i) a significant increasing monotonic correlation between the days of our timecourse and the number of actively transcribed protein-coding genes and long intergenic non-coding RNAs (lincRNAs) (P < 0.05), consistent with the transcriptional complexity of the brain, (ii) an increase in CpG methylation after neural differentiation that resembled the epigenomic signature of the endogenous tissue, and (iii) a significant decreasing monotonic correlation between the days of our timecourse and the percent of in vitro to brain-tissue differences (P < 0.05) for tissue-specific protein-coding genes and all putative lincRNAs. These studies support the utility of autopsy donors' somatic cells for iPSC-based neurological disease models, and provide evidence that in vitro neural differentiation can result in physiologically progression.
ContributorsHjelm, Brooke E (Author) / Craig, David W. (Thesis advisor) / Wilson-Rawls, Norma J. (Thesis advisor) / Huentelman, Matthew J. (Committee member) / Mason, Hugh S. (Committee member) / Kusumi, Kenro (Committee member) / Arizona State University (Publisher)
Created2013
Description
A literature review summarizing the current status of conservation efforts of the Mojave Desert tortoise (Gopherus agassizii) including a brief overview of the Endangered Species Act (ESA) and its applicability to this species' conservation. A genetic and physiological comparison of the morphologically similar Mojave species with the Sonoran (Gopherus morafkai) species proceeded by an analysis of if and how the ESA should apply to the Sonoran population. Analysis of current plans and interagency cooperations followed by a multi-step proposal on how best to conserve the Sonoran population of Desert tortoise.
ContributorsKulik, Elise Chikako (Author) / Kusumi, Kenro (Thesis director) / Tollis, Marc (Committee member) / Wilson Sayres, Melissa (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
The purpose of this thesis is to compare ecolabeling to conservation easements for facilitating multi-use land between food production and conservation. Biodiversity has been on the decline as human agriculture uses more land. According to Encyclopedia Britannica “Half of the world’s habitable land (some 51 million square km [19.7 million square miles]) has been converted to agriculture, and some 77 percent of agricultural land (some 40 million square km [15.4 million square miles]) is used for grazing by cattle, sheep, goats, and other livestock. This massive conversion of forests, wetlands, grasslands, and other terrestrial ecosystems has produced a 60 percent decline (on average) in the number of vertebrates worldwide since 1970”(Rafferty 2010). The purpose of this paper is to explore ways individual landowners and private businesses can continue to operate profitably on their land while reversing the harmful loss to biodiversity observed in the past 50 years. Two of the most popular methods of achieving conservation on workable land are ecolabeling and conservation easements.
ContributorsWilcox, Christopher James (Author) / Leonard, Brian (Thesis director) / Schoon, Michael (Committee member) / Dean, W.P. Carey School of Business (Contributor) / Department of Supply Chain Management (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12
Description
Wound healing is a complex tissue response that requires a coordinated interplay of multiple cells in orchestrated biological processes to restore the skin's barrier function post-injury. Proteolytic enzymes, in particular matrix metalloproteinases (MMPs), contribute to all phases of the healing process by regulating immune cell influx, clearing out the extracellular matrix (ECM), and remodeling scar tissue. As a result of these various functions in the healing of skin wounds, uncontrolled activities of MMPs are associated with impaired wound healing. The MMP gene family consists of a highly conserved set of genes. Deleterious mutations in MMP genes cause developmental phenotypes that affect the heart, skeleton, and immune system response.
The availability of contiguous draft genomes of non-model organisms enables the study of gene families through analysis of synteny and sequence identity. My project is aimed at conducting a comparative genomic analysis of the MMP gene family from the genomes of 29 tetrapod species—with an emphasis on reptiles. Results regarding the similarities and differences among MMP protein sequences can be further investigated to shed light on the causes which give rise to various adaptive mutations for specific species groups.
ContributorsYu, Alexander (Author) / Kusumi, Kenro (Thesis director) / Dolby, Greer (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2022-12
Description
The climate conversation is growing more important and necessary than ever. The media has a way of promoting a "doom and gloom" sentiment over conservation efforts and what the public has the power to do in terms of making a change. Now due to the effects of COVID-19 on the population's attention spans and memories, there is a need for a way to communicate climate science effectively and to encourage those who feel discouraged by climate change to find their inner power. The answer lies in photography. Making science accessible and intriguing through the art of photography is what can get people more interested and empowered to fight against climate change and alter their attitudes towards environmentalism. This thesis explains psychological research and the reasons why people feel helpless in terms of our global future. In then dives into human subjects research conducted on ASU's campus and how the survey results argue in favor of the paper's hypothesis. Additionally, ways to get involved and reasons why we need to remain hopeful are discussed.
ContributorsGorlick, Vanessa (Author) / Hall, Sharon (Thesis director) / Makings, Elizabeth (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / The Sidney Poitier New American Film School (Contributor) / Dean, W.P. Carey School of Business (Contributor)
Created2023-05
Description
With human populations continuing to expand, encounters with wildlife become more frequent, and more people have the ability to go hunting. When it comes to top level predators, there have often been questions raised about the effects hunting has on their populations. Some speculate there are compensatory measures as a result, others that hunting has an additive mortality effect. The purpose of this project was to do a literature review over the topic of hunting mountain lions in order to definitively determine what the effects of hunting are on their populations. It was concluded that hunting has a negative impact on mountain lion populations, having an additive effect on their mortality rate, reducing their genetic biodiversity, reducing their rate of emigration/immigration, and changing their population demographics.
ContributorsDaily, Austin (Author) / Senko, Jesse (Thesis director) / Bennett, Ira (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of Sustainability (Contributor) / Dean, W.P. Carey School of Business (Contributor)
Created2022-05
Description
Terrestrial hermit crabs serve an incredibly important ecological role in seed dispersal and as decomposers along coastal shorelines. They have also become quite popular in the commercial pet trade, with one species, Coenobita clypeatus, being particularly favored. Typically, these hermit crabs are easily captured and removed from the wild with little protection in their native ranges. In Hermitage Bay, Tobago, there is little information about the population numbers, composition, shell preference, and substrate preference of C. clypeatus in their native habitat. In this study, we estimated population size, gastropod shell preferences, and substrate preference conditions when clustering. We conducted mark re-capture surveys in March, July, and December 2023 and collected morphological data from captured hermit crabs. Our results indicate that the estimated population was highest in July, with the variation being significant when using the Schnabel mark re-capture estimation formula. The most common overall shell type, Columbella mercatoria (West Indian Dove Shell), was prevalent among the smaller sized, younger hermit crabs; while the larger hermit crabs preferred Cittarium pica (West Indian Top Shell). The most preferred substrate for these terrestrial hermit crabs were areas with a mixture of sand and dirt, with high amounts of vegetation and leaf waste and low amounts of human litter. These results suggest a predominantly young population and that beach cleanups should focus on removing human litter entirely, while leaving leaf waste and other fallen logs and branches and not using the collected decomposing plant matter for bonfires. This can help maintain a healthy hermit crab population that continues to benefit the coastlines in Tobago as well as other ecosystems.
ContributorsLindteigen, Amy (Author) / Briggs, Georgette (Thesis director) / Mohammed, Ryan (Committee member) / Barrett, The Honors College (Contributor) / College of Integrative Sciences and Arts (Contributor) / Dean, W.P. Carey School of Business (Contributor)
Created2024-05
Description
In the U.S., breast cancer (BC) incidences among African American (AA) and CA (CA) women are similar, yet AA women have a significantly higher mortality rate. In addition, AA women often present with tumors at a younger age, with a higher tumor grade/stage and are more likely to be diagnosed with the highly aggressive triple-negative breast cancer (TNBC) subtype. Even within the TNBC subtype, AA women have a worse clinical outcome compared to CA. Although multiple socio-economic and lifestyle factors may contribute to these observed health disparities, it is essential that the underlying biological differences between CA and AA TNBC are identified. In this study, gene expression profiling was performed on archived FFPE samples, obtained from CA and AA women diagnosed with early stage TNBC. Initial analysis revealed a pattern of differential expression in the AA cohort compared to CA. Further molecular characterization results showed that the AA cohort segregated into 3-TNBC molecular subtypes; Basal-like (BL2), Immunomodulatory (IM) and Mesenchymal (M). Gene expression analyses resulted in 190 differentially expressed genes between the AA and CA cohorts. Pathway enrichment analysis demonstrated that differentially expressed genes were over-represented in cytoskeletal remodeling, cell adhesion, tight junctions, and immune response in the AA TNBC -cohort. Furthermore, genes in the Wnt/β-catenin pathway were over-expressed. These results were validated using RT-qPCR on an independent cohort of FFPE samples from AA and CA women with early stage TNBC, and identified Caveolin-1 (CAV1) as being significantly expressed in the AA-TNBC cohort. Furthermore, CAV1 was shown to be highly expressed in a cell line panel of TNBC, in particular, those of the mesenchymal and basal-like molecular subtype. Finally, silencing of CAV1 expression by siRNA resulted in a significant decrease in proliferation in each of the TNBC cell lines. These observations suggest that CAV1 expression may contribute to the more aggressive phenotype observed in AA women diagnosed with TNBC.
ContributorsGetz, Julie (Author) / Baumbach-Reardon, Lisa L (Thesis advisor) / Lake, Douglas F (Thesis advisor) / Bussey, Kimberly (Committee member) / Kusumi, Kenro (Committee member) / Arizona State University (Publisher)
Created2015
Description
Rapid advancements in genomic technologies have increased our understanding of rare human disease. Generation of multiple types of biological data including genetic variation from genome or exome, expression from transcriptome, methylation patterns from epigenome, protein complexity from proteome and metabolite information from metabolome is feasible. "Omics" tools provide comprehensive view into biological mechanisms that impact disease trait and risk. In spite of available data types and ability to collect them simultaneously from patients, researchers still rely on their independent analysis. Combining information from multiple biological data can reduce missing information, increase confidence in single data findings, and provide a more complete view of genotype-phenotype correlations. Although rare disease genetics has been greatly improved by exome sequencing, a substantial portion of clinical patients remain undiagnosed. Multiple frameworks for integrative analysis of genomic and transcriptomic data are presented with focus on identifying functional genetic variations in patients with undiagnosed, rare childhood conditions. Direct quantitation of X inactivation ratio was developed from genomic and transcriptomic data using allele specific expression and segregation analysis to determine magnitude and inheritance mode of X inactivation. This approach was applied in two families revealing non-random X inactivation in female patients. Expression based analysis of X inactivation showed high correlation with standard clinical assay. These findings improved understanding of molecular mechanisms underlying X-linked disorders. In addition multivariate outlier analysis of gene and exon level data from RNA-seq using Mahalanobis distance, and its integration of distance scores with genomic data found genotype-phenotype correlations in variant prioritization process in 25 families. Mahalanobis distance scores revealed variants with large transcriptional impact in patients. In this dataset, frameshift variants were more likely result in outlier expression signatures than other types of functional variants. Integration of outlier estimates with genetic variants corroborated previously identified, presumed causal variants and highlighted new candidate in previously un-diagnosed case. Integrative genomic approaches in easily attainable tissue will facilitate the search for biomarkers that impact disease trait, uncover pharmacogenomics targets, provide novel insight into molecular underpinnings of un-characterized conditions, and help improve analytical approaches that use large datasets.
ContributorsSzelinger, Szabolcs (Author) / Craig, David W. (Thesis advisor) / Kusumi, Kenro (Thesis advisor) / Narayan, Vinodh (Committee member) / Rosenberg, Michael S. (Committee member) / Huentelman, Matthew J (Committee member) / Arizona State University (Publisher)
Created2015