Matthew MacDonald’s research utilizes cutting-edge mass spectrometry-based proteomic approaches to elucidate the molecular pathology of schizophrenia, bipolar disorder and autism through the study of synaptic protein networks in human postmortem brain tissue. His research program is broken up into three interrelated tracks:

1. The development and validation of proteomic approaches to assay human postmortem brain tissue. New approaches focus on increasing the spatial resolution of proteomics assays (e.g., specific cortical layers, cell types and cellular microdomains), increasing the types of post-translational modifications that can be reliably measured in human postmortem brain tissue, and utilizing subject and cohort transcript databases to enhance isoform-specific quantification as well as the integration of proteomic data with genomics and transcriptomics.

2. The application of these proteomic approaches, along with genetics, transcriptomics, microscopy and bioinformatics, to investigate associations between genetic risk, synaptic protein network alterations and cytoarchitectonic pathology in these conditions.

3. Evaluating the downstream effects of select synaptic protein alterations in animal and cell culture model systems.