Research Areas
Our research aims to understand how different neuronal populations regulate presynaptic function, from neurotransmitter release to the maintenance of protein homeostasis. Through this work, we hope to advance our understanding of the mechanisms of information processing that fulfill the requirements of diverse brain functions, from learning and memory to the relay of sensory information, and to bring us closer to elucidating the sources of selective vulnerability in aging and neurodegenerative diseases.
Molecular Mechanism of Neuromodulator Release
Most of the research leading to the uncovering of the mechanism of neurotransmitter release has been conducted in systems relying on fast synaptic signaling. Much less is known about the molecular processes regulating the release of modulatory transmitters like the monoamines dopamine, serotonin and norepinephrine, even though they regulate many essential brain functions from movement to mood and attention. Our comparative proteomics study revealed differences in the composition of synaptic vesicles storing monoamines compared to the fast synaptic transmitter glutamate. We focus on understanding how these differences in synaptic vesicle composition affect how these transmitters are released in response to different activity patterns and how this ultimately regulates behavior.
Role and Regulation of Neurotransmitter Corelease
Many neurons release more than one neurotransmitter, but the role and mechanism of neurotransmitter corelease remain incompletely understood. Our previous work revealed that in neurons releasing dopamine and glutamate, the two transmitters are stored in functionally distinct vesicles and their release differs in responsiveness to changes in neuronal firing frequency. We aim to understand how neurons assure the independent release of two transmitters and how these two signaling systems communicate with different postsynaptic target cells, affecting information relay in brain circuits.
Diversity of Presynaptic Protein Homeostasis Among Vulnerable and Resilient Neurons
In many neurodegenerative diseases like Parkinson’s or Alzheimer’s disease, select neuronal populations are lost while adjacent neurons remain relatively intact. Presynaptic terminals and axons are often the first cellular compartments affected in neurodegenerative diseases, and vulnerable neurons often contain aggregates of misfolded protein, implicating disruptions in presynaptic protein homeostasis in the disease process. We aim to investigate whether resilient and vulnerable neuronal populations differ in active protein degradation pathways or the subcellular localization of components of the protein homeostasis machinery. Our aim is to advance our understanding of the sources of selective neuronal vulnerability in aging and neurodegeneration.