Departmental Affiliation(s): Chemical and Systems Biology
Graduate Program(s): Neurosciences, Chemical and Systems Biology

Email: ricardo.dolmetsch@stanford.edu
Website: http://www.stanford.edu/group/dolmetschlab

About the PI

Research Interests:

Molecular mechanisms of calcium channel signalling in the nervous and cardiovascular systems. Development of new technologies to investigate signalling cascades in intact animals and to investigate the functions of neuronal circuits in the brain.

Keywords:

Calcium, ion channels, neuroscience, cardiovascular system, signalling, gene expression, cellular motility, imaging, neuronal circuits

Research Description: 

Changes in cytoplasmic calcium play a central role in converting electrical events at the cell membrane into the activation of enzymatic cascades in the cytoplasm of cells. We are interested in understanding how intracellular calcium activates the signalling pathways that regulate the survival, motility and morphology of neurons and muscle cells. One of the main projects in the laboratory is to identify the full set of proteins that are associated with voltage gated calcium channels using a variety of proteomic approaches. In parallel we are characterizing the function of specific channel-interacting proteins using a multidisciplinary approach that includes digital calcium imaging, electrophysiology, in vitro cell biological assays and genetically engineered mice. We are also searching for small molecules that disrupt the interaction between calcium channels and their associated proteins as a way of developing new pharmaceuticals that modulate calcium signalling.

A second project of the laboratory is to determine how different temporal and spatial patterns of cytoplasmic calcium regulate the expression of genes in the nervous system.   We are developing ways of profiling gene expression in single neurons stimulated with defined patterns of intracellular calcium that are associated with cell differentiation and plasticity in the nervous system. 

A final interest of the laboratory is to develop new ways of manipulating and visualizing intracellular signalling cascades in neuronal circuits.   We are engineering methods to rapidly degrade specific signalling molecules in intact animals and we are developing methods for observing biochemical events in the whole tissues.   Together with our studies of calcium signalling, these new technologies will advance our understanding of neuronal function and provide new treatments for neurological and cardiovascular diseases. 

Lab members:

Max Dolmetsch (PB, Principal Baby)

Representative Publications:

R.E. Dolmetsch, U. Pajvani, K. Fife, J.M. Spotts, M.E. Greenberg (2001) Signaling to the nucleus by an L-type calcium channel-calmodulin complex via the MAP kinase pathway. Science 294:333-339

J.M. Spotts^*, R.E. Dolmetsch^*, M.E. Greenberg (2002) Time-lapse imaging of a dynamic phosphorylation-dependent protein-protein interaction in mammalian cells. Procedings National Academy of Sciences USA 99:15142-7.

R.E. Dolmetsch, K. Xu, and R.S. Lewis (1998) Calcium oscillations increase the efficiency and specificity of gene expression. Nature 392:933-36

R.E. Dolmetsch, R.S. Lewis, C.C. Goodnow, and J.I. Healy. (1997) Differential activation of transcription factors by calcium response amplitude and duration. Nature 386:855-58

S. Feske, J. Giltnane, R. E. Dolmetsch, L.M. Staudt and A. Rao. (2001) Gene regulation mediated by calcium signals in T lymphocytes. Nature Immunology 2:316-24.

J.M. Kornhauser , C.W. Cowan , A.J. Shaywitz , R.E. Dolmetsch , E.C. Griffith , L.S. Hu, C. Haddad , Z. Xia , M.E. Greenberg. (2002)CREB transcriptional activity in neurons is regulated by multiple, calcium-specific phosphorylation events. Neuron 34:221-33.