Faculty and Staff

In 2014/2015, Arizona State University (ASU) Libraries, the Labriola National American Indian Data Center, and the ASU American Indian Studies Department completed an ASU Institute for Humanities Research (IHR) seed grant entitled “Carlos Montezuma’s Wassaja Newsletter: Digitization, Access and Context” to digitize all ASU held issues of the newsletter Wassaja Freedom’s Signal for the Indian, which Yavapai activist-intellectual Carlos Montezuma, MD (1866-1923) self-published during 1916-1922. The grant team additionally selected a portion of the ASU Libraries Carlos Montezuma archival collection for digitization to provide a more complete picture of Dr. Carlos Montezuma’s life and work.

The ASU grant team produced a searchable online collection on the ASU Digital Repository and created an online exhibition in conjunction with the IHR Nexus Lab’s Developing Wassaja Project. The Nexus Lab’s role at ASU is to grow the digital humanities through interdisciplinary collaborations bringing together humanities, science, and technology. The Nexus Lab partnered with the grant team to create the Developing Wassaja Project which provided an opportunity for faculty, staff, and students at ASU to engage in electronic publication through web application development.

The resulting web platform, Wassaja: A Carlos Montezuma Project, provides context for this digitized collection and facilitates community interaction, including a partnership with Dr. Montezuma’s home community the Fort McDowell Yavapai Nation. In this webcast, Digital Projects Librarian Matthew Harp, Developing Wassaja Project team member Joe Buenker (subject librarian), and grant team member Joyce Martin (librarian and curator of the Labriola National American Indian Data Center) will discuss and demonstrate the resources created and the resulting partnership with the Fort McDowell Yavapai Nation. The webcast will focus on identifying collaborators and needed skills to engage in Digital Humanities research and on identifying the stages of a collaborative project.

Participants will gain insight on working directly with diverse communities; overcoming technical limitations of traditional institutional repositories; collaborative strategies with faculty, research centers, and cultural heritage societies; solutions for moving hidden collections into an engaging digital exhibition; integrating digital humanities research and instruction with library curation; and preparing for long term costs and management issues.

Anthropology librarian Juliann Couture and Joyce Martin, curator of the Labriola National American Indian Data Center, looking at the Center's display of unique Hopi Kachina dolls. Four of the kachinas (Navan Kachina; Talavi Kachina; Flute Kachina; and Ahöla Kachina) were created by artist, carver, and former ASU employee Tony Dukepoo as a gift to the libraries in 1979. The kachina dolls are on display in the Labriola Center located on the 2nd floor of the Hayden Library on ASU's Tempe campus.

The Simon Ortiz and Labriola Center Lecture on Indigenous Land, Culture, and Community addresses topics and issues across disciplines in the arts, humanities, sciences, and politics. Underscoring Indigenous American experiences and perspectives, this Series seeks to create and celebrate knowledge that evolves from an Indigenous worldview that is inclusive and that is applicable to all walks of life.” Professor Simon Ortiz discussed the overall nature of the Series, especially emphasizing the global nature of Indigenous concerns. Joyce Martin and Matthew Harp elaborated on the contributions of the Labriola National American Indian Data Center and ASU Libraries to the Series.

The Labriola Center hosts an informal event in Hayden Library which facilitates close interaction between the featured speaker and audience members. The ASU Libraries records the evening lectures which take place at the Heard Museum and presents both an audio podcast and streaming video of each lecture on the ASU Library Channel webpage. This lecture series provides not only a chance for community discussion at the events themselves, but through the innovative use of technology the ASU Libraries enables additional forums for discussion in blogs and web pages which choose to link to the streaming videos.

To address the need to study frozen clinical specimens using next-generation RNA, DNA, chromatin immunoprecipitation (ChIP) sequencing and protein analyses, we developed a biobank work flow to prospectively collect biospecimens from patients with renal cell carcinoma (RCC). We describe our standard operating procedures and work flow to annotate pathologic results and clinical outcomes. We report quality control outcomes and nucleic acid yields of our RCC submissions (N=16) to The Cancer Genome Atlas (TCGA) project, as well as newer discovery platforms, by describing mass spectrometry analysis of albumin oxidation in plasma and 6 ChIP sequencing libraries generated from nephrectomy specimens after histone H3 lysine 36 trimethylation (H3K36me3) immunoprecipitation. From June 1, 2010, through January 1, 2013, we enrolled 328 patients with RCC. Our mean (SD) TCGA RNA integrity numbers (RINs) were 8.1 (0.8) for papillary RCC, with a 12.5% overall rate of sample disqualification for RIN <7. Banked plasma had significantly less albumin oxidation (by mass spectrometry analysis) than plasma kept at 25°C (P<.001). For ChIP sequencing, the FastQC score for average read quality was at least 30 for 91% to 95% of paired-end reads. In parallel, we analyzed frozen tissue by RNA sequencing; after genome alignment, only 0.2% to 0.4% of total reads failed the default quality check steps of Bowtie2, which was comparable to the disqualification ratio (0.1%) of the 786-O RCC cell line that was prepared under optimal RNA isolation conditions. The overall correlation coefficients for gene expression between Mayo Clinic vs TCGA tissues ranged from 0.75 to 0.82. These data support the generation of high-quality nucleic acids for genomic analyses from banked RCC. Importantly, the protocol does not interfere with routine clinical care. Collections over defined time points during disease treatment further enhance collaborative efforts to integrate genomic information with outcomes.

Insulin-like growth factor 1 (IGF1) is an important biomarker for the management of growth hormone disorders. Recently there has been rising interest in deploying mass spectrometric (MS) methods of detection for measuring IGF1. However, widespread clinical adoption of any MS-based IGF1 assay will require increased throughput and speed to justify the costs of analyses, and robust industrial platforms that are reproducible across laboratories. Presented here is an MS-based quantitative IGF1 assay with performance rating of >1,000 samples/day, and a capability of quantifying IGF1 point mutations and posttranslational modifications. The throughput of the IGF1 mass spectrometric immunoassay (MSIA) benefited from a simplified sample preparation step, IGF1 immunocapture in a tip format, and high-throughput MALDI-TOF MS analysis. The Limit of Detection and Limit of Quantification of the resulting assay were 1.5 μg/L and 5 μg/L, respectively, with intra- and inter-assay precision CVs of less than 10%, and good linearity and recovery characteristics. The IGF1 MSIA was benchmarked against commercially available IGF1 ELISA via Bland-Altman method comparison test, resulting in a slight positive bias of 16%. The IGF1 MSIA was employed in an optimized parallel workflow utilizing two pipetting robots and MALDI-TOF-MS instruments synced into one-hour phases of sample preparation, extraction and MSIA pipette tip elution, MS data collection, and data processing. Using this workflow, high-throughput IGF1 quantification of 1,054 human samples was achieved in approximately 9 hours. This rate of assaying is a significant improvement over existing MS-based IGF1 assays, and is on par with that of the enzyme-based immunoassays. Furthermore, a mutation was detected in ∼1% of the samples (SNP: rs17884626, creating an A→T substitution at position 67 of the IGF1), demonstrating the capability of IGF1 MSIA to detect point mutations and posttranslational modifications.

Serum Amyloid A (SAA) is an acute phase protein complex consisting of several abundant isoforms. The N- terminus of SAA is critical to its function in amyloid formation. SAA is frequently truncated, either missing an arginine or an arginine-serine dipeptide, resulting in isoforms that may influence the capacity to form amyloid. However, the relative abundance of truncated SAA in diabetes and chronic kidney disease is not known.

Methods: Using mass spectrometric immunoassay, the abundance of SAA truncations relative to the native variants was examined in plasma of 91 participants with type 2 diabetes and chronic kidney disease and 69 participants without diabetes.

Results: The ratio of SAA 1.1 (missing N-terminal arginine) to native SAA 1.1 was lower in diabetics compared to non-diabetics (p = 0.004), and in males compared to females (p<0.001). This ratio was negatively correlated with glycated hemoglobin (r = −0.32, p<0.001) and triglyceride concentrations (r = −0.37, p<0.001), and positively correlated with HDL cholesterol concentrations (r = 0.32, p<0.001).

Conclusion: The relative abundance of the N-terminal arginine truncation of SAA1.1 is significantly decreased in diabetes and negatively correlates with measures of glycemic and lipid control.

Background: Cysteine sulfenic acid (Cys-SOH) plays important roles in the redox regulation of numerous proteins. As a relatively unstable posttranslational protein modification it is difficult to quantify the degree to which any particular protein is modified by Cys-SOH within a complex biological environment. The goal of these studies was to move a step beyond detection and into the relative quantification of Cys-SOH within specific proteins found in a complex biological setting--namely, human plasma.

Results: This report describes the possibilities and limitations of performing such analyses based on the use of thionitrobenzoic acid and dimedone-based probes which are commonly employed to trap Cys-SOH. Results obtained by electrospray ionization-based mass spectrometric immunoassay reveal the optimal type of probe for such analyses as well as the reproducible relative quantification of Cys-SOH within albumin and transthyretin extracted from human plasma--the latter as a protein previously unknown to be modified by Cys-SOH.

Conclusions: The relative quantification of Cys-SOH within specific proteins in a complex biological setting can be accomplished, but several analytical precautions related to trapping, detecting, and quantifying Cys-SOH must be taken into account prior to pursuing its study in such matrices.

Quiescin sulfhydryl oxidase 1 (QSOX1) is a highly conserved disulfide bond-generating enzyme that is overexpressed in diverse tumor types. Its enzymatic activity promotes the growth and invasion of tumor cells and alters extracellular matrix composition. In a nude mouse-human tumor xenograft model, tumors containing shRNA for QSOX1 grew significantly more slowly than controls, suggesting that QSOX1 supports a proliferative phenotype in vivo. High throughput screening experiments identified ebselen as an in vitro inhibitor of QSOX1 enzymatic activity. Ebselen treatment of pancreatic and renal cancer cell lines stalled tumor growth and inhibited invasion through Matrigel in vitro. Daily oral treatment with ebselen resulted in a 58% reduction in tumor growth in mice bearing human pancreatic tumor xenografts compared to controls. Mass spectrometric analysis of ebselen-treated QSOX1 mechanistically revealed that C165 and C237 of QSOX1 covalently bound to ebselen. This report details the anti-neoplastic properties of ebselen in pancreatic and renal cancer cell lines. The results here offer a “proof-of-principle” that enzymatic inhibition of QSOX1 may have clinical relevancy.