A major focus of our research is regulation of glutamate receptors that play key roles in neuronal communication. Failure to regulate these receptors can cause seizure disorders and neurodegeneration such as, Alzheimer's, Huntington's and Parkinson's disease. We have identified proteins that control the movement and localization of these receptors at synapses with the aim of designing drugs that prevent neuronal death in disease states.
We also study Angelman syndrome. Our suggest that defective brain-derived neurotrophic factor (BDNF)/TrkB receptor signaling is responsible for observed cognitive impairment in humans. At synapses, the activation of NMDA type glutamate receptors promotes the release of brain-derived neurotrophic factor (BDNF), which stimulates TrkB-PLCγ-CaMKII/CaMKIV-CREB and PI3K-Akt signaling pathways, required for the induction and maintenance of LTP. We identified the synaptic scaffolding protein postsynaptic density-95 (PSD-95) as a novel drug target in the BDNF signaling pathway, and designed a novel prototypic cyclic peptide drug, CN2097, that reinstates BDNF signaling and long-term potentiation (LTP) in AS mice.
I became interested in this line of research because I was interested in processes such as learning and memory. Receptors are key elements in the communication of neurons and by studying them we hope to understand at the molecular level how the brain functions.