Matthew MacDonald |
2024-04-20 |
Matthew MacDonald ,Ph.D. Throughout his graduate and postdoctoral training to his current position as an assistant professor of psychiatry, University of Pittsburgh, MacDonald's main research focus has been validating and utilizing proteomic approaches to investigate synaptic protein network dysfunction in postmortem brain tissue from patients with neuropsychiatric disease. As a postdoctoral fellow (with Drs. Robert Sweet and Nathan Yates) and now a faculty member he has continued to push the envelope of proteomics approaches in human postmortem brain tissue to increase proteomic depth, throughput and spatial resolution.
Multi-omics Approach Identifies Pathological Phosphorylation Events Driving Synapse Loss in Schizophrenia
Schizophrenia is a complex trait disorder in which genetic risk factors converge on synaptic protein networks, altering synaptic architecture, and impairing brain function. Synaptic protein network features include protein expression, trafficking, and activity. To assess interactions between these features, we utilized microscopy as well as targeted and label free mass spectrometry to quantify synapse number and size as well as protein expression, synaptic protein levels, and protein phosphorylation in cortical tissue from 50 schizophrenia and 50 matched control subjects. Read More To enhance the value of these data sets generated with skyline, we utilized co-regulation network and cross-network analyses; identifying a set of altered phosphorylations on f-acting binding and glutamate receptor trafficking proteins strongly correlated with both synaptic protein level alterations and synapse loss in schizophrenia. CRISPR-Cas9 was used to generate phosphomimetic mice for select phospho-alterations and confirm their causality in proteome and spine pathology.
[PDF]