We are addressing key issues in molecular neurobiology and molecular cardiology: how hormones and neurotransmitters regulate the function of cardiac cells and neurons, by acting on G proteins that transmit the signal, and ion channels – proteins that underlie the electrical activity in these cells; how these functions are altered in disease; and, whenever possible, seek for treatments for the accompanying disorders. We focus on open issues in this field: protein complexes and the biochemical cascades involved in modulation of ion channels; cellular, biophysical and biochemical mechanisms that underlie the function of proteins responsible for excitability; changes in their function as a result of genetic disorders, cardiac disease and neurologic disorders. The diseases currently in focus are GNB1 Encephalopathy and epilepsy. The laboratory uses animal and cell models and a wide range of methodologies: recombinant DNA and molecular biology; protein biochemistry; kinetic/math modeling; molecular modeling; biophysics; electrophysiology; optical methods; cell culture; and other.

​

We are recruiting M.Sc. and Ph.D. candidates and postdocs - see Join Us!

 

Main projects in the lab:

 

1. Molecular mechanisms of function and regulation of G protein activated K+ channels (GIRK). These proteins are major mediators of inhibitory effects of neurotransmitters in heart and brain. We study the regulation of these channels by receptors and G protein subunits, interactions within this protein molecule and the formation of signaling complexes with other proteins, the importance of diversity of GIRK genes in their function, their role in regulation of excitability in neurons and in disease.

2. The function of cardiac calcium channels and their regulation by auxiliary proteins, by the diversity of their isoforms (alternative splicing/posttranslational modifications), with current emphasis on fundamental and previously poorly understood aspects of adrenergic (adrenalin & noradrenalin) regulation of these channels.

3. Etiology and mechanisms of GNB1 Encephalopathy, a recently discovered neurologic disorder, caused by mutations in Gβ1 subunit of G proteins. Our studies revealed that different mutations that cause this disease, differentially and specifically affect distinct functions of the Gβ protein. In particular, they alter the regulation of GIRK channels, and affect transmitter release. Based on these findings, we currently work toward the development of treatments for GNB1-accompanying epilepsy. This work involves mouse models, human patients, and several model systems.

4. Regulation of transmitter and hormone release by neurotransmitters and G proteins (in collaboration with Prof. Ilana Lotan). Effects of G proteins and disease-causing mutations are studied in cultured secretory cells and mouse neurons.