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- Creators: Sierks, Michael
- Creators: Chakrabarti, Chaitali
Description
Specificity and affinity towards a given ligand/epitope limit target-specific delivery. Companies can spend between $500 million to $2 billion attempting to discover a new drug or therapy; a significant portion of this expense funds high-throughput screening to find the most successful target-specific compound available. A more recent addition to discovering highly specific targets is the application of phage display utilizing single chain variable fragment antibodies (scFv). The aim of this research was to employ phage display to identify pathologies related to traumatic brain injury (TBI), particularly astrogliosis. A unique biopanning method against viable astrocyte cultures activated with TGF-β achieved this aim. Four scFv clones of interest showed varying relative affinities toward astrocytes. One of those four showed the ability to identify reactive astroctyes over basal astrocytes through max signal readings, while another showed a statistical significance in max signal reading toward basal astrocytes. Future studies will include further affinity characterization assays. This work contributes to the development of targeting therapeutics and diagnostics for TBI.
ContributorsMarsh, William (Author) / Stabenfeldt, Sarah (Thesis advisor) / Caplan, Michael (Committee member) / Sierks, Michael (Committee member) / Arizona State University (Publisher)
Created2013
Description
The goal of this thesis is to test whether Alzheimer's disease (AD) is associated with distinctive humoral immune changes that can be detected in plasma and tracked across time. This is relevant because AD is the principal cause of dementia, and yet, no specific diagnostic tests are universally employed in clinical practice to predict, diagnose or monitor disease progression. In particular, I describe herein a proteomic platform developed at the Center for Innovations in Medicine (CIM) consisting of a slide with 10.000 random-sequence peptides printed on its surface, which is used as the solid phase of an immunoassay where antibodies of interest are allowed to react and subsequently detected with a labeled secondary antibody. The pattern of antibody binding to the microarray is unique for each individual animal or person. This thesis will evaluate the versatility of the microarray platform and how it can be used to detect and characterize the binding patterns of antibodies relevant to the pathophysiology of AD as well as the plasma samples of animal models of AD and elderly humans with or without dementia. My specific aims were to evaluate the emergence and stability of immunosignature in mice with cerebral amyloidosis, and characterize the immunosignature of humans with AD. Plasma samples from APPswe/PSEN1-dE9 transgenic mice were evaluated longitudinally from 2 to 15 months of age to compare the evolving immunosignature with non-transgenic control mice. Immunological variation across different time-points was assessed, with particular emphasis on time of emergence of a characteristic pattern. In addition, plasma samples from AD patients and age-matched individuals without dementia were assayed on the peptide microarray and binding patterns were compared. It is hoped that these experiments will be the basis for a larger study of the diagnostic merits of the microarray-based immunoassay in dementia clinics.
ContributorsRestrepo Jimenez, Lucas (Author) / Johnston, Stephen A. (Thesis advisor) / Chang, Yung (Committee member) / Reiman, Eric (Committee member) / Sierks, Michael (Committee member) / Arizona State University (Publisher)
Created2011
How Does Technology Development Influence the Assessment of Parkinson’s Disease? A Systematic Review
Description
Parkinson’s disease (PD) is a neurological disorder with complicated and disabling motor and non-motor symptoms. The pathology for PD is difficult and expensive. Furthermore, it depends on patient diaries and the neurologist’s subjective assessment of clinical scales. Objective, accurate, and continuous patient monitoring have become possible with the advancement in mobile and portable equipment. Consequently, a significant amount of work has been done to explore new cost-effective and subjective assessment methods or PD symptoms. For example, smart technologies, such as wearable sensors and optical motion capturing systems, have been used to analyze the symptoms of a PD patient to assess their disease progression and even to detect signs in their nascent stage for early diagnosis of PD.
This review focuses on the use of modern equipment for PD applications that were developed in the last decade. Four significant fields of research were identified: Assistance diagnosis, Prognosis or Monitoring of Symptoms and their Severity, Predicting Response to Treatment, and Assistance to Therapy or Rehabilitation. This study reviews the papers published between January 2008 and December 2018 in the following four databases: Pubmed Central, Science Direct, IEEE Xplore and MDPI. After removing unrelated articles, ones published in languages other than English, duplicate entries and other articles that did not fulfill the selection criteria, 778 papers were manually investigated and included in this review. A general overview of PD applications, devices used and aspects monitored for PD management is provided in this systematic review.
This review focuses on the use of modern equipment for PD applications that were developed in the last decade. Four significant fields of research were identified: Assistance diagnosis, Prognosis or Monitoring of Symptoms and their Severity, Predicting Response to Treatment, and Assistance to Therapy or Rehabilitation. This study reviews the papers published between January 2008 and December 2018 in the following four databases: Pubmed Central, Science Direct, IEEE Xplore and MDPI. After removing unrelated articles, ones published in languages other than English, duplicate entries and other articles that did not fulfill the selection criteria, 778 papers were manually investigated and included in this review. A general overview of PD applications, devices used and aspects monitored for PD management is provided in this systematic review.
ContributorsDeb, Ranadeep (Author) / Ogras, Umit Y. (Thesis advisor) / Shill, Holly (Committee member) / Chakrabarti, Chaitali (Committee member) / Arizona State University (Publisher)
Created2019
Description
This project aims to address the current protocol regarding the diagnosis and treatment of traumatic brain injury (TBI) in medical industries around the world. Although there are various methods used to qualitatively determine if TBI has occurred to a patient, this study attempts to aid in the creation of a system for quantitative measurement of TBI and its relative magnitude. Through a method of artificial evolution/selection called phage display, an antibody that binds highly specifically to a post-TBI upregulated brain chondroitin sulfate proteoglycan called neurocan has been identified. As TG1 Escheria Coli bacteria were infected with KM13 helper phage and M13 filamentous phage in conjunction, monovalent display of antibody fragments (ScFv) was performed. The ScFv bind directly to the neurocan and from screening, phage that produced ScFv's with higher affinity and specificity to neurocan were separated and purified. Future research aims to improve the ScFv characteristics through increased screening toward neurocan. The identification of a highly specific antibody could lead to improved targeting of neurocan post-TBI in-vivo, aiding researchers in quantitatively defining TBI by visualizing its magnitude.
ContributorsSeelig, Timothy Scott (Author) / Stabenfeldt, Sarah (Thesis director) / Ankeny, Casey (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05