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dc.contributor.advisorZaia, Josephen_US
dc.contributor.authorRaghunathan, Rekhaen_US
dc.date.accessioned2019-11-25T19:09:48Z
dc.date.available2019-11-25T19:09:48Z
dc.date.issued2019
dc.identifier.urihttps://hdl.handle.net/2144/38588
dc.description.abstractParkinson’s disease (PD) is a neurological disorder characterized by the lack of functional dopaminergic neurons in the nigrostriatal pathway in the brain. Current therapeutic strategies for the disease provide temporary symptomatic relief. Gene therapy has the potential to improve dopamine production in Parkinson’s disease patients. Adeno-associated viruses (AAV) are the vectors of choice in gene therapy for PD, due to their well-characterized safety and efficacy profiles, with all primary receptors being glycans. The problem with using AAV in PD gene therapy is that the aged brain is resistant to transduction of the virus, while PD primarily occurs with age. Thus, in Aim 1 we characterize the age-related changes in glycan receptors in the nigrostriatal pathway as a baseline to address current challenges in gene delivery in Parkinson’s disease. To make these measurements from specific regions of tissue, we develop a platform that incorporates on-slide digestion followed by LC-MS/MS for integrated glycomics and proteomics. Further, we apply this to understand aging- and PD-related changes in the human pre-frontal cortex in Aims 2 and 3, to understand normal and pathological aging processes as well as integrate this information with transcriptomics data, to assess risk factors that may contribute to Parkinson’s disease. Finally, we also apply the method to investigate cancer premalignancy and heterogeneity. Our on-slide method, used herein to study aging, Parkinson’s disease and cancer, can be applied to any precious biopsy specimens to enable glycomic and proteomic profiling in diverse diseases, and thus may have a broad impact on biomedical research.en_US
dc.language.isoen_US
dc.rightsAttribution 4.0 Internationalen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectBiochemistryen_US
dc.subjectAgingen_US
dc.subjectCanceren_US
dc.subjectGlycomicsen_US
dc.subjectMulti-omicsen_US
dc.subjectParkinson's diseaseen_US
dc.subjectProteomicsen_US
dc.titleIntegrated glycomics and proteomics in aging, Parkinson's disease and canceren_US
dc.typeThesis/Dissertationen_US
dc.date.updated2019-10-07T19:02:51Z
etd.degree.nameDoctor of Philosophyen_US
etd.degree.leveldoctoralen_US
etd.degree.disciplineMolecular and Translational Medicineen_US
etd.degree.grantorBoston Universityen_US
dc.identifier.orcidhttps://orcid.org/0000-0003-0778-1973


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International