Nitric Oxide Signaling in Metabolism
Our laboratory investigates the biological chemistry and signaling pathways of nitric oxide by using biochemical and molecular methodologies in partnership with mass spectroscopy-based approaches. We uncovered that selective modification of cysteine residue by nitric oxide to generate S-nitrosocysteine regulates the function of enzymes participating in metabolism and mitochondrial bioenergetics. Current efforts are centered on uncovering the importance of S-nitrosocysteine in the regulation of β-oxidation of fatty acids and in the coordination of liver responses to metabolic deprivation or overloading. Another project investigates the utility of pharmacological agents that restore nitric oxide signaling to treat long-chain fatty acid oxidation disorders.
Neurophysiology and Neurobiology of Disease
We are generating inventories of cellular proteomes and secretomes of the mouse brain. These inventories are used to create 3D-functional landscapes of the mouse brain extracellular space and to identify astrocyte secreted proteins that influence neuronal development and neuronal demise. Other studies explore the role of nitric oxide and nitric-oxide mediated protein S-nitrosylation in the neuron-astrocyte metabolism of glutamate. Lastly, we are investigating the molecular and biochemical mechanisms of α-synuclein aggregation and neurotoxicity in Parkinson’s disease and related neurodegenerative disorders. Current investigations explore the relationship between dopamine-induced oxidative biochemistry with the formation of potentially toxic α-synuclein oligomers, the native conformations of α-synuclein and the influence of post-translational modifications in the aggregation of α-synuclein in mouse models.