My laboratory is interested in mechanisms of molecular memory and their use in cellular signal transduction and neuronal function. In the nervous system, we want to know how the ability of proteins to "remember" past molecular events is implemented in synaptic plasticity underlying the ability of our brains to learn and retain memories. CaMKII, a Ca2+ activated protein kinase highly enriched in brain, is an ideal model protein for the investigation of these questions. Ca2+ and CaMKII are required in several forms of synaptic plasticity and learning, and CaMKII displays several interesting forms of molecular memory. Molecular memory enables CaMKII to integrate Ca2+ signals over time and to act as molecular decoder of Ca2+ spike frequencies. Our primary goal is to better understand the mechanisms underlying neuronal plasticity and learning, but our research also has direct implication for stroke and neurodegenerative diseases.
Ca2+ signaling has important functions also outside the nervous system, including heart function, muscle contraction, and insulin secretion. My lab is also interested in how these functions are regulated by CaMKII; some of the cellular mechanisms may be similar to those used by neurons. Frequency decoding, for instance, makes CaMKII an ideal candidate for a molecular heart rate sensor, and roles of CaMKII in heart diseases such as dilated hypertrophy are emerging.
The tools we use in our research include molecular manipulations of neurons and other cells in tissue culture, live imaging of labeled proteins within cells, and biochemical analysis of purified proteins in vitro (including regulation of activity, protein-protein interactions, and modes of frequency detection).