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Matthew MacDonald, Ph.D., throughout his graduate and postdoctoral training to his current position as an Assistant Professor of Psychiatry, University of Pittsburgh, Matthew's main focus of research has been validating and utilizing targeted proteomics approaches to investigate synaptic protein network dysfunction in postmortem brain tissue from patients with neuropsychiatric disease. As a graduate student at the University of Pennsylvania, Matthew worked with Drs. Chang-Gyu Hahn and Ian Blair to validate a biochemical fractionation – targeted proteomics approach for protein quantification in synaptic microdomain enrichments from human postmortem brain tissue of schizophrenia subjects. As a postdoctoral fellow with Drs. Robert Sweet and Nathan Yates, University of Pittsburgh, he eveloped a laser capture microdissection - targeted proteomics approach for multiplexed protein quantification in discreet cortical layers from human brain tissue.
Synaptic Protein Networks in Neuropsychiatric DiseaseSynaptic architecture and its adaptive remodeling require complex molecular events involving thousands of proteins. Read MoreMany neuropsychiatric illnesses are complex trait disorders in which multiple genetic risk factors converge on neuronal protein networks, altering synaptic architecture and impairing brain function. A quantitative window into the synaptic proteome of brain tissue from patients is essential to understanding this neuropsychiatric disease pathogenesis. Utilizing targeted proteomics, paired with biochemical fraction or laser capture microdissection, we investigated synaptic protein expression in postmortem brain tissue from patients with schizophrenia and Alzheimer’s disease. To enhance the value of these data sets generated with skyline, we utilized weighted co-expression networking analyses to identify links between risk alleles, synaptic protein network features, and known synaptic architecture alterations in these diseases. For example, we recently identified a module of co-expressed proteins, observed only in schizophrenia, whose expression is strongly linked to cortical spine loss, a well-documented synaptic architectural abnormality.
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