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Bridging the gap between protein-tyrosine phosphorylation networks, metabolism and physiology in liver-specific PTP1b deletion mice

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dc.contributor.advisor Forest M. White. en_US
dc.contributor.author Miraldi, Emily R. (Emily Rae) en_US
dc.contributor.other Massachusetts Institute of Technology. Computational and Systems Biology Program. en_US
dc.date.accessioned 2012-09-13T18:54:11Z
dc.date.available 2012-09-13T18:54:11Z
dc.date.copyright 2012 en_US
dc.date.issued 2012 en_US
dc.identifier.uri http://hdl.handle.net/1721.1/72824
dc.description Thesis (Ph. D.)--Massachusetts Institute of Technology, Computational and Systems Biology Program, 2012. en_US
dc.description Cataloged from PDF version of thesis. en_US
dc.description Includes bibliographical references. en_US
dc.description.abstract Metabolic syndrome describes a complex set of obesity-related disorders that enhance diabetes, cardiovascular, and mortality risk. Studies of liver-specific protein-tyrosine phosphatase lb (PTPlb) deletion mice (L-PTPlb-/-) suggests that hepatic PTPlb inhibition would mitigate metabolic syndrome progression through amelioration of hepatic insulin resistance, endoplasmic reticulum stress, and whole-body lipid metabolism. However, the network alterations underlying these phenotypes are poorly understood. Mass spectrometry was used to quantitatively discover protein phosphotyrosine network changes in L-PTP lb-/- mice relative to control mice under both normal and high-fat diet conditions. A phosphosite set enrichment analysis was developed to identify numerous pathways exhibiting PTPlb- and diet-dependent phosphotyrosine regulation. Detection of PTP lb-dependent phosphotyrosine sites on lipid metabolic proteins initiated global lipidomics characterization of corresponding liver samples and revealed altered fatty acid and triglyceride metabolism in L-PTPlb-/- mice. Multivariate modeling techniques were developed to infer molecular dependencies between phosphosites and lipid metabolic changes, resulting in quantitatively predictive phenotypic models. en_US
dc.description.statementofresponsibility by Emily R. Miraldi. en_US
dc.format.extent 182 p. en_US
dc.language.iso eng en_US
dc.publisher Massachusetts Institute of Technology en_US
dc.rights M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. en_US
dc.rights.uri http://dspace.mit.edu/handle/1721.1/7582 en_US
dc.subject Computational and Systems Biology Program. en_US
dc.title Bridging the gap between protein-tyrosine phosphorylation networks, metabolism and physiology in liver-specific PTP1b deletion mice en_US
dc.type Thesis en_US
dc.description.degree Ph.D. en_US
dc.contributor.department Massachusetts Institute of Technology. Computational and Systems Biology Program. en_US
dc.identifier.oclc 806957068 en_US


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