The Screening and Application of Biomarkers in Autoimmune Disease

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dc.contributor.advisorMohan, Chandra
dc.contributor.committeeMemberWillson, Richard C.
dc.contributor.committeeMemberShevkoplyas, Sergey S.
dc.contributor.committeeMemberWu, Tianfu
dc.contributor.committeeMemberDu, Yong
dc.creatorSoomro, Sanam
dc.creator.orcid0000-0001-8729-4897
dc.date.accessioned2020-01-07T03:43:28Z
dc.date.createdDecember 2018
dc.date.issued2018-12
dc.date.submittedDecember 2018
dc.date.updated2020-01-07T03:43:29Z
dc.description.abstractThis research portrays three aspects of the biomarker development pipeline: screening for stool biomarkers for pediatric inflammatory bowel disease (pIBD), validation of urine normalizer proteins, and translation of lupus nephritis (LN) urine biomarkers to phosphor-based lateral flow assays (LFAs). As the diagnosis of pIBD is invasive and painful for children, two high- throughput technologies utilizing aptamers and antibodies have been used to screen over 1000 human proteins for noninvasive stool biomarkers for the two types of pIBD: Crohn’s disease (CD) and ulcerative colitis (UC). The screens have uncovered 119 proteins elevated in both CD and UC stool, 19 proteins elevated in CD stool, 124 proteins elevated in UC stool, and 58 proteins dysregulated between CD and UC stool. ELISA validation of 23 proteins has uncovered 9 biomarkers for IBD, 1 biomarker for CD, 9 biomarkers for UC, and 10 biomarkers that distinguish UC from CD. Many hits have been implicated in the intestinal mucosa of pIBD patients and in inflammatory and other immunologic disease pathways. These biomarkers can aid in pIBD diagnosis and help elucidate the mechanisms of this complicated disease. To increase the sensitivity of urine biomarkers in diagnostics, most quantitative biomarkers are normalized to creatinine to account for urine production. Creatinine is a small metabolite and antibodies to creatinine are difficult to develop, limiting the applications of quantitative urine diagnostics. An aptamer screen of 1000 proteins and ELISA validation has identified HVEM for the normalization of ALCAM and other urine biomarkers for LN. To translate urine protein biomarkers for LN diagnostics to the point-of-care, sensitive and quantitative phosphor LFAs for the detection of ALCAM, an LN biomarker, and HVEM, a urine normalizer, have been created and optimized showing a limit of detection of 125 pg/mL in buffer. As this is the first application of nanophosphors in urine, the feasibility of nanophosphor use in urine has been evaluated and optimized showing detection limits around 5 ng/ml in urine. Although the current limit for the assay in urine is above the clinical range of ALCAM and HVEM, this work has created a foundation for the application of nanophosphors for the detection of urinary ALCAM and HVEM.
dc.description.departmentBiomedical Engineering, Department of
dc.format.digitalOriginborn digital
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/10657/5827
dc.language.isoeng
dc.rightsThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).
dc.subjectProteomics
dc.subjectBiomarkers
dc.subjectAutoimmune
dc.subjectInflammatory bowel disease
dc.subjectUrine
dc.subjectStool
dc.subjectLateral flow assay
dc.subjectLupus nephritis
dc.subjectSLE
dc.subjectIB
dc.subjectSystemic Lupus Erythematosus
dc.subjectDiagnostics
dc.subjectPoint-of-care
dc.titleThe Screening and Application of Biomarkers in Autoimmune Disease
dc.type.dcmiText
dc.type.genreThesis
local.embargo.lift2020-12-01
local.embargo.terms2020-12-01
thesis.degree.collegeCullen College of Engineering
thesis.degree.departmentBiomedical Engineering, Department of
thesis.degree.disciplineBiomedical Engineering
thesis.degree.grantorUniversity of Houston
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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