Our main interest is in calcium signaling. Calcium ion (Ca2+) acts as an intracellular second messenger in living cells. Changes in the cytosolic Ca2+ level influence most fundamental cellular processes. Deranged calcium signaling results in a number of disorders. Local and rapid changes in cytosolic Ca2+ are evoked by activation of plasma membrane voltage-gated Ca2+ channels in response to membrane depolarization. Global changes in cytosolic Ca2+ are supported by intracellular Ca2+ release channels - the inositol (1,4,5)-trisphosphate receptor (InsP3R) and ryanodine receptor (RyanR). The functional properties and modulation of intracellular Ca2+ release channels and voltage-gated Ca2+ channels is the focus of our research.
The main directions of our research are:
Structure-function and modulation of the inositol trisphosphate receptor (InsP3R)
We use molecular, biochemical, imaging, and electrophysiological methods to study properties of InsP3R [1, 2, 6, 10, 11, 15, 19, 22, 23, 24, 13, 14, 18, 13, 21]. Our emphasis is on understanding how the activity of these channels is modulated.
Deranged calcium signaling and neurodegenerative disorders
In the course of our studies of InsP3R we discovered a connection between deranged neuronal calcium signaling and Huntington's disease (HD) [16, 20, 27, 33, 35, 38, 39, 41, 43, 44, 49, 53, 56]. Currently we are expanding this area of research to other neurodegenerative diseases, such as spinocerebellar ataxia type 3 (SCA3) , spinocerebellar ataxia type 2 (SCA2) [46, 58, 59] and Alzheimer's Disease (AD) [31, 34, 50, 51, 54]. We are also developing new therapeutic agents for HD and AD [55, 60] and study structures of proteins involved in neurodegenerative disorders [47, 61]. We hope that our research will help in developing therapeutics for these incurable and lethal disorders.
Synaptic voltage-gated calcium channels
In the nervous system, secretion of neurotransmitter is triggered by Ca2+ influx via presynaptic voltage-gated Ca2+ channels. We are trying to understand the molecular mechanisms involved in targeting voltage-gated Ca2+ channels to synpatic locations [3, 12, 25, 26, 30]. This work also prompted us to examine general rules that govern PDZ domain ligand specificty using a bioinformatics approach  and to develop a high-throughput screen for small molecule PDZ domain inhibitors .