Faculty and Staff

Background: Cancer diagnosis in both dogs and humans is complicated by the lack of a non-invasive diagnostic test. To meet this clinical need, we apply the recently developed immunosignature assay to spontaneous canine lymphoma as clinical proof-of-concept. Here we evaluate the immunosignature as a diagnostic for spontaneous canine lymphoma at both at initial diagnosis and evaluating the disease free interval following treatment.

Methods: Sera from dogs with confirmed lymphoma (B cell n = 38, T cell n = 11) and clinically normal dogs (n = 39) were analyzed. Serum antibody responses were characterized by analyzing the binding pattern, or immunosignature, of serum antibodies on a non-natural sequence peptide microarray. Peptides were selected and tested for the ability to distinguish healthy dogs from those with lymphoma and to distinguish lymphoma subtypes based on immunophenotype. The immunosignature of dogs with lymphoma were evaluated for individual signatures. Changes in the immunosignatures were evaluated following treatment and eventual relapse.

Results: Despite being a clonal disease, both an individual immunosignature and a generalized lymphoma immunosignature were observed in each dog. The general lymphoma immunosignature identified in the initial set of dogs (n = 32) was able to predict disease status in an independent set of dogs (n = 42, 97% accuracy). A separate immunosignature was able to distinguish the lymphoma based on immunophenotype (n = 25, 88% accuracy). The individual immunosignature was capable of confirming remission three months following diagnosis. Immunosignature at diagnosis was able to predict which dogs with B cell lymphoma would relapse in less than 120 days (n = 33, 97% accuracy).

Conclusion: We conclude that the immunosignature can serve as a multilevel diagnostic for canine, and potentially human, lymphoma.

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.

There are an increasing variety of applications in which peptides are both synthesized and used attached to solid surfaces. This has created a need for high throughput sequence analysis directly on surfaces. However, common sequencing approaches that can be adapted to surface bound peptides lack the throughput often needed in library-based applications. Here we describe a simple approach for sequence analysis directly on solid surfaces that is both high speed and high throughput, utilizing equipment available in most protein analysis facilities. In this approach, surface bound peptides, selectively labeled at their N-termini with a positive charge-bearing group, are subjected to controlled degradation in ammonia gas, resulting in a set of fragments differing by a single amino acid that remain spatially confined on the surface they were bound to. These fragments can then be analyzed by MALDI mass spectrometry, and the peptide sequences read directly from the resulting spectra.

Recent infectious outbreaks highlight the need for platform technologies that can be quickly deployed to develop therapeutics needed to contain the outbreak. We present a simple concept for rapid development of new antimicrobials. The goal was to produce in as little as one week thousands of doses of an intervention for a new pathogen. We tested the feasibility of a system based on antimicrobial synbodies. The system involves creating an array of 100 peptides that have been selected for broad capability to bind and/or kill viruses and bacteria. The peptides are pre-screened for low cell toxicity prior to large scale synthesis. Any pathogen is then assayed on the chip to find peptides that bind or kill it. Peptides are combined in pairs as synbodies and further screened for activity and toxicity. The lead synbody can be quickly produced in large scale, with completion of the entire process in one week.

Antigen-antibody complexes are central players in an effective immune response. However, finding those interactions relevant to a particular disease state can be arduous. Nonetheless many paths to discovery have been explored since deciphering these interactions can greatly facilitate the development of new diagnostics, therapeutics, and vaccines. In silico B cell epitope mapping approaches have been widely pursued, though success has not been consistent. Antibody mixtures in immune sera have been used as handles for biologically relevant antigens, but these and other experimental approaches have proven resource intensive and time consuming. In addition, these methods are often tailored to individual diseases or a specific proteome, rather than providing a universal platform. Most of these methods are not able to identify the specific antibody’s epitopes from unknown antigens, such as un-annotated neo antigens in cancer. Alternatively, a peptide library comprised of sequences unrestricted by naturally-found protein space provides for a universal search for mimotopes of an antibody’s epitope. Here we present the utility of such a non-natural random sequence library of 10,000 peptides physically addressed on a microarray for mimotope discovery without sequence information of the specific antigen. The peptide arrays were probed with serum from an antigen-immunized rabbit, or alternatively probed with serum pre-absorbed with the same immunizing antigen. With this positive and negative screening scheme, we identified the library-peptides as the mimotopes of the antigen. The unique library peptides were successfully used to isolate antigen-specific antibodies from complete immune serum. Sequence analysis of these peptides revealed the epitopes in the immunized antigen. We present this method as an inexpensive, efficient method for identifying mimotopes of any antibody’s targets. These mimotopes should be useful in defining both components of the antigen-antibody complex.

Immunosignaturing shows promise as a general approach to diagnosis. It has been shown to detect immunological signs of infection early during the course of disease and to distinguish Alzheimer’s disease from healthy controls. Here we test whether immunosignatures correspond to clinical classifications of disease using samples from people with brain tumors. Blood samples from patients undergoing craniotomies for therapeutically naïve brain tumors with diagnoses of astrocytoma (23 samples), Glioblastoma multiforme (22 samples), mixed oligodendroglioma/astrocytoma (16 samples), oligodendroglioma (18 samples), and 34 otherwise healthy controls were tested by immunosignature. Because samples were taken prior to adjuvant therapy, they are unlikely to be perturbed by non-cancer related affects. The immunosignaturing platform distinguished not only brain cancer from controls, but also pathologically important features about the tumor including type, grade, and the presence or absence of O⁶-methyl-guanine-DNA methyltransferase methylation promoter (MGMT), an important biomarker that predicts response to temozolomide in Glioblastoma multiformae patients.