Matching Items (214)
Description
Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains a major clinical challenge. The local tumor microenvironment plays a significant role in cancer metastasis, where tumor cells respond and adapt to a plethora of biochemical and biophysical signals from stromal cells and extracellular matrix (ECM) proteins. Due to these complexities, there is a critical need to understand molecular mechanisms underlying cancer metastasis to facilitate the discovery of more effective therapies. In the past few years, the integration of advanced biomaterials and microengineering approaches has initiated the development of innovative platform technologies for cancer research. These technologies enable the creation of biomimetic in vitro models with physiologically relevant (i.e. in vivo-like) characteristics to conduct studies ranging from fundamental cancer biology to high-throughput drug screening. In this review article, we discuss the biological significance of each step of the metastatic cascade and provide a broad overview on recent progress to recapitulate these stages using advanced biomaterials and microengineered technologies. In each section, we will highlight the advantages and shortcomings of each approach and provide our perspectives on future directions.
ContributorsPeela, Nitish (Author) / Nikkhah, Mehdi (Thesis director) / LaBaer, Joshua (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Glioblastoma is the most aggressive and lethal brain tumor, due to its resistance to current conventional therapy. The resistance to chemo- and radiotherapy has been attributed to a special population of cells known as glioma stem cells. Previous literature has shown the importance of a Central Nervous System-restricted transcription factor OLIG2 in maintaining the tumor-propagating potential of these glioma stem cells. OLIG2's function was further elucidated, with its pro-mitogenic function due to its ability to negatively regulate the p53 pathway by suppressing the acetylation of the p53 protein's C terminal domain. Past work in our lab has confirmed that one of OLIG2's partner proteins is Histone Deacetylase 1 (HDAC1). In vitro experiments have also shown that targeting HDAC1 using hairpin RNA in glioma stem cells negatively impacts proliferation. In a survival study using a murine glioma model, targeting Hdac1 using hairpin RNA is shown to reduce tumor burden and increase survival. In this paper, we demonstrate that silencing Hdac1 expression reduces proliferation, increases cell death, likely a result of increased acetylation of p53. Olig2 expression levels seem to be unaffected in GSCs, demonstrating that the Hdac1 protein ablation is indeed lethal to GSCs. This work builds upon previously collected results, confirming that Hdac1 is a potential surrogate target for Olig2's pro-mitotic function in regulating the p53 pathway.
ContributorsLoo, Vincent You Wei (Author) / LaBaer, Joshua (Thesis director) / Mehta, Shwetal (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
CREB3L1 has been previously shown to auto-acetylate itself when prepared from HeLa cell based in vitro protein expression lysates. To circumvent the concerns of the contamination of co-purified human proteins from HeLa lysates, the protein was purified through insect cell transfection in vitro. The objective of this study was to assay the auto-acetylation activity of CREB3L1 prepared from insect cells using the baculovirus expression vector system (BEVS). To this end, His-tagged CREB3L1 was affinity purified from Hi5 cells using an IMAC column and used for acetylation assay. Samples were taken different time points and auto-acetylation was by western using antibodies specific to acetylated lysines. Auto-acetylation activity was observed after overnight incubation. Future experiments will focus on the improvement of purification yield and the identification of the substrates and interacting proteins of CREB3L1 to better understand the biological functions of this novel acetyltransferase.
ContributorsSchwab, Anna (Author) / LaBaer, Joshua (Thesis director) / Qiu, Ji (Committee member) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Historically, studies of condition-dependent signals in animals have been male-centric, but recent work suggests that female ornaments can also communicate individual quality (e.g., disease state, fecundity). There has been a surge of interest in how urbanization alters signaling traits, but we know little about if and how cities affect signal expression in female animals. We measured carotenoid-based plumage coloration and coccidian (Isospora spp) parasite burden in desert and city populations of house finches to examine urban impacts on male and female health and attractiveness. In earlier work, we showed that male house finches are less colorful and more parasitized in the city, and we again detected that pattern in this study for males. However, though city females are also less colorful than their rural counterparts, we found that rural females were more parasitized. Also, regardless of sex and unlike rural birds, more colorful birds in the city were more heavily infected with coccidia. These results show that urban environments can disrupt signal honesty in female animals and highlight the need for more studies on how cities affect disease and condition-dependent traits in both male and female animals.
ContributorsSykes, Brooke Emma (Author) / McGraw, Kevin (Thesis director) / Sweazea, Karen (Committee member) / Hutton, Pierce (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Almost every form of cancer deregulates the expression and activity of anabolic glycosyltransferase (GT) enzymes, which incorporate particular monosaccharides in a donor acceptor as well as linkage- and anomer-specific manner to assemble complex and diverse glycans that significantly affect numerous cellular events, including tumorigenesis and metastasis. Because glycosylation is not template-driven, GT deregulation yields heterogeneous arrays of aberrant intact glycan products, some in undetectable quantities in clinical bio-fluids (e.g., blood plasma). Numerous glycan features (e.g., 6 sialylation, β-1,6-branching, and core fucosylation) stem from approximately 25 glycan “nodes:” unique linkage specific monosaccharides at particular glycan branch points that collectively confer distinguishing features upon glycan products. For each node, changes in normalized abundance (Figure 1) may serve as nearly 1:1 surrogate measure of activity for culpable GTs and may correlate with particular stages of carcinogenesis. Complementary to traditional top down glycomics, the novel bottom-up technique applied herein condenses each glycan node and feature into a single analytical signal, quantified by two GC-MS instruments: GCT (time-of-flight analyzer) and GCMSD (transmission quadrupole analyzers). Bottom-up analysis of stage 3 and 4 breast cancer cases revealed better overall precision for GCMSD yet comparable clinical performance of both GC MS instruments and identified two downregulated glycan nodes as excellent breast cancer biomarker candidates: t-Gal and 4,6-GlcNAc (ROC AUC ≈ 0.80, p < 0.05). Resulting from the activity of multiple GTs, t-Gal had the highest ROC AUC (0.88) and lowest ROC p‑value (0.001) among all analyzed nodes. Representing core-fucosylation, glycan node 4,6-GlcNAc is a nearly 1:1 molecular surrogate for the activity of α-(1,6)-fucosyltransferase—a potential target for cancer therapy. To validate these results, future projects can analyze larger sample sets, find correlations between breast cancer stage and changes in t-Gal and 4,6-GlcNAc levels, gauge the specificity of these nodes for breast cancer and their potential role in other cancer types, and develop clinical tests for reliable breast cancer diagnosis and treatment monitoring based on t-Gal and 4,6-GlcNAc.
ContributorsZaare, Sahba (Author) / Borges, Chad (Thesis director) / LaBaer, Joshua (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
There are two electrophysiological states of sleep in birds (rapid-eye-movement sleep [REM] and slow-wave sleep [SWS]), which have different functions and costs. REM improves memory consolidation, while SWS is neuro-restorative but also exposes the animal to more risk during this deep-sleep phase. Birds who sleep in more exposed microsites are known to invest proportionally less in SWS (presumably to ensure proper vigilance), but otherwise little else is known about the ecological or behavioral predictors of how much time birds devote to REM v. SWS sleep. In this comparative analysis, we examine how proportional time spent in SWS v. REM is related to brain mass and duration of the incubation period in adults. Brain mass and incubation period were chosen as predictors of sleep state investment because brain mass is positively correlated with body size (and may show a relationship between physical development and sleep) and incubation period can be a link used to show similarities and differences between birds and mammals (using mammalian gestation period). We hypothesized that (1) species with larger brains (relative to body size and also while controlling for phylogeny) would have higher demands for information processing, and possibly proportionally outweigh neuro-repair, and thus devote more time to REM and that (2) species with longer incubation periods would have proportionally more REM due to the extended time required for overnight predator vigilance (and not falling into deep sleep) while on the nest. We found, using neurophysiological data from literature on 27 bird species, that adults from species with longer incubation periods spent proportionally more time in REM sleep, but that relative brain size was not significantly associated with relative time spent in REM or SWS. We therefore provide evidence that mammalian and avian REM in response to incubation/gestation period have convergently evolved. Our results suggest that overnight environmental conditions (e.g. sleep site exposure) might have a greater effect on sleep parameters than gross morphological attributes.
ContributorsRaiffe, Joshua Sapell (Author) / McGraw, Kevin (Thesis director) / Deviche, Pierre (Committee member) / Hutton, Pierce (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Humans have greatly altered the night-time photic environment via the production of artificial light at night (ALAN; e.g. street lights, car traffic, billboards, lit buildings). ALAN is problematic because it may significantly alter the seasonal/daily physiological rhythms or behaviors of animals. There has been considerable interest in the impacts of ALAN on health in humans and lab animals, but most such work has centered on adults and we know comparatively little about effects on young animals. We exposed 3-week-old king quail (Excalfactoria chinensis) to a constant overnight blue-light regime for 6 weeks and assessed weekly bactericidal activity of plasma against Escherichia coli - a commonly employed metric of innate immunity in animals. We found that chronic ALAN exposure significantly increased immune function, and that this elevation in immune performance manifested at different developmental time points in males and females. These results counter the pervasive notion that overnight light exposure is universally physiologically harmful to diurnal organisms and indicate that ALAN can provide sex-specific, short-term immunological boosts to developing animals.
ContributorsSaini, Chandan (Author) / McGraw, Kevin (Thesis director) / Hutton, Pierce (Committee member) / Sweazea, Karen (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
Disturbances in the protein interactome often play a large role in cancer progression. Investigation of protein-protein interactions (PPI) can increase our understanding of cancer pathways and will disclose unknown targets involved in cancer disease biology. Although numerous methods are available to study protein interactions, most platforms suffer from drawbacks including high false positive rates, low throughput, and lack of quantification. Moreover, most methods are not compatible for use in a clinical setting. To address these limitations, we have developed a multiplexed, in-solution protein microarray (MISPA) platform with broad applications in proteomics. MISPA can be used to quantitatively profile PPIs and as a robust technology for early detection of cancers. This method utilizes unique DNA barcoding of individual proteins coupled with next generation sequencing to quantitatively assess interactions via barcode enrichment. We have tested the feasibility of this technology in the detection of patient immune responses to oropharyngeal carcinomas and in the discovery of novel PPIs in the B-cell receptor (BCR) pathway. To achieve this goal, 96 human papillomavirus (HPV) antigen genes were cloned into pJFT7-cHalo (99% success) and pJFT7-n3xFlag-Halo (100% success) expression vectors. These libraries were expressed via a cell-free in vitro transcription-translation system with 93% and 96% success, respectively. A small-scale study of patient serum interactions with barcoded HPV16 antigens was performed and a HPV proteome-wide study will follow using additional patient samples. In addition, 15 query proteins were cloned into pJFT7_nGST expression vectors, expressed, and purified with 93% success to probe a library of 100 BCR pathway proteins and detect novel PPIs.
ContributorsRinaldi, Capria Lakshmi (Author) / LaBaer, Joshua (Thesis director) / Mangone, Marco (Committee member) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Solar energy has become one of the most popular renewable energy in human’s life because of its abundance and environment friendliness. To achieve high solar energy conversion efficiency, it usually requires surfaces to absorb selectivity within one spectral range of interest and reflect strongly over the rest of the spectrum. An economic method is always desired to fabricate spectrally selective surfaces with improved energy conversion efficiency. Colloidal lithography is a recently emerged way of nanofabrication, which has advantages of low-cost and easy operation.
In this thesis, aluminum metasurface structures are proposed based on colloidal lithography method. High Frequency Structure Simulator is used to numerically study optical properties and design the aluminum metasurfaces with selective absorption. Simulation results show that proposed aluminum metasurface structure on aluminum oxide thin film and aluminum substrate has a major reflectance dip, whose wavelength is tunable within the near-infrared and visible spectrum with metasurface size. As the metasurface is opaque due to aluminum film, it indicates strong wavelength-selective optical absorption, which is due to the magnetic resonance between the top metasurface and bottom Al film within the aluminum oxide layer.
The proposed sample is fabricated based on colloidal lithography method. Monolayer polystyrene particles of 500 nm are successfully prepared and transferred onto silicon substrate. Scanning electron microscope is used to check the surface topography. Aluminum thin film with 20-nm or 50-nm thickness is then deposited on the sample. After monolayer particles are removed, optical properties of samples are measured by micro-scale optical reflectance and transmittance microscope. Measured and simulated reflectance of these samples do not have frequency selective properties and is not sensitive to defects. The next step is to fabricate the Al metasurface on Al_2 O_3 and Al films to experimentally demonstrate the selective absorption predicted from the numerical simulation.
In this thesis, aluminum metasurface structures are proposed based on colloidal lithography method. High Frequency Structure Simulator is used to numerically study optical properties and design the aluminum metasurfaces with selective absorption. Simulation results show that proposed aluminum metasurface structure on aluminum oxide thin film and aluminum substrate has a major reflectance dip, whose wavelength is tunable within the near-infrared and visible spectrum with metasurface size. As the metasurface is opaque due to aluminum film, it indicates strong wavelength-selective optical absorption, which is due to the magnetic resonance between the top metasurface and bottom Al film within the aluminum oxide layer.
The proposed sample is fabricated based on colloidal lithography method. Monolayer polystyrene particles of 500 nm are successfully prepared and transferred onto silicon substrate. Scanning electron microscope is used to check the surface topography. Aluminum thin film with 20-nm or 50-nm thickness is then deposited on the sample. After monolayer particles are removed, optical properties of samples are measured by micro-scale optical reflectance and transmittance microscope. Measured and simulated reflectance of these samples do not have frequency selective properties and is not sensitive to defects. The next step is to fabricate the Al metasurface on Al_2 O_3 and Al films to experimentally demonstrate the selective absorption predicted from the numerical simulation.
ContributorsGuan, Chuyun (Author) / Wang, Liping (Thesis advisor) / Azeredo, Bruno (Committee member) / Wang, Robert (Committee member) / Arizona State University (Publisher)
Created2019
Description
Biogas’s potential as a renewable fuel source has been an area of increased research in recent years. One issue preventing wide-spread use of biogas as a fuel is the trace amounts of impurities that damage fuel-burning equipment by depositing silicon, sulfur, calcium and other elements on their surface. This study aims to analyze the effects of a high concentration of L4 linear siloxane on solid oxide fuel cell performance until failure occurs. L4 siloxane has not been extensively researched previously, and this investigation aims to provide new data to support similar, though slower, degradation compared to D4, D5 and other siloxanes in solid oxide fuel cells. The experiments were conducted inside a furnace heated to 800℃ with an Ni-YSZ-supported (Nickel-yttria-stabilized zirconia) fuel cell. A fuel source with a flow rate of 20 mL/min of hydrogen gas, 10 mL/min of nitrogen gas and 0.15 mL/min of L4 siloxane was used. Air was supplied to the cathode. The effects of siloxane deposition on cell voltage and power density degradation and resistance increase were studied by using techniques like the current-voltage method, electrochemical impedance spectroscopy, and gas chromatography. The results of the experiment after reduction show roughly constant degradation of 8.35 mV/hr, followed after approximately 8 hours by an increasing degradation until cell failure of 130.45 mV/hr. The initial degradation and stagnation match previous research in siloxane deposition on SOFCs, but the sharp decline to failure does not. A mechanism for solid oxide fuel cell failure is proposed based on the data.
ContributorsRiley, Derall M. (Author) / Milcarek, Ryan J (Thesis advisor) / Wang, Liping (Committee member) / Phelan, Patrick E (Committee member) / Arizona State University (Publisher)
Created2021