Research Interests
The gene ANK3 has been identified as a significant risk locus for bipolar disorder (BD). It encodes the protein ankyrin-G, which is essential in the formation of neuronal subdomains including the nodes of Ranvier and the axon initial segment. We have recently discovered that ankyrin-G is also essential to the development of GABAergic synapses. These synapses are vital for synchronization of neuronal networks and are often dysregulated in BD patients. We have identified a BD patient family containing the ANK3 mutation p.W1989R. This mutation abolishes the interaction between the GABAA receptor-associated protein (GABARAP) and ankyrin-G, resulting in significant decrease of GABAergic synapses, especially from parvalbumin-expressing interneurons. Fibroblasts from the patient family will be utilized to generate induced pluripotent stem cell (iPSC)-derived neurons. These neurons will be utilized to gain understanding into how commonly used therapeutics including lithium, valproate, and lamotrigine affect ankyrin-G-dependent GABAergic circuits in a BD patient genetic background.
Faculty Advisor
