BBS Faculty Member - Thomas Schwarz

Thomas Schwarz

Department of Neurology

Boston Children's Hospital
Neuroscience, CLS Bldg., Rm. 12-130
3 Blackfan Circle
Boston, MA 02115
Tel: 617-919-2219
Fax: 617-919-2771
Email: thomas.schwarz@childrens.harvard.edu
Lab Members: 8 postdoctoral fellows, 5 graduate students
Visit my lab page here.



The research interests of the Schwarz lab are centered on the use of genetics to probe the cell biology of the nervous system. We use Drosophila, mouse, and rat neurons to investigate such topics as 1) the manner in which membrane organelles are moved along axons, with a particular interest in mitochondria; 2) the mechanism by which a synapse forms and is modified; 3) the mechanism by which neurotransmitters are secreted at synapses; and 4) membrane trafficking in non-neuronal cells. Although our projects typically begin with a genetic focus, they also include electrophysiological, biochemical, and cell biological methods for characterizing mutants and proteins. These investigations, though focused on basic mechanisms, are relevant to the pathology of developmental disorders of the brain and to neurodegeneration.

Recent findings include the following:

1) A mutant screen for blind flies that has uncovered two genes that prevent the formation of synapses. One of these is a motor protein that is necessary to bring synaptic cargos to the site of synapse formation. The other is a protein of the cell surface that is necessary for endings to acquire the correct shape.

2) Elucidation of the mechanism by which mitochondria are transported and the regulation of that movement by cytoplasmic Ca++ and posttranslational modifications of the motor/adaptor complex

3) Demonstrating that two Parkinson’s Disease genes, PINK1 and Parkin, stop mitochondrial movement by the sequential phosphorylation, ubiquitination, and degradation of Miro, a component of the motor/adaptor complex.

4) Finding a novel signaling pathway by which synaptic activity causes membrane to be added at the synapse and consequent growth of the postsynaptic specialization.



Last Update: 6/2/2014



Publications

For a complete listing of publications click here.

 


 

Kurshan, P.T., Oztan, A. and Schwarz, T.L. (2009) Presynaptic α2δ-3 protein is required for synaptic morphogenesis independent of its Ca++-channel functions. Nature Neuroscience 12:1411-1419.

Wang, X. and Schwarz, T.L. (2009) The mechanism of Ca++ regulation of kinesin-mediated mitochondrial motility.
Cell 136:163-174.

Wang, X., Winter, D., Ashrafi, G., Schlehe, J., Wong, Y.L., Selkoe, D., Rice, S.J., Steen, J., LaVoie, M.J., and Schwarz, T.L. (2011) PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility.
Cell 147:893-907

Teodoro, R.O., Pekkurnaz, G., Nasser, A., Higashi-Kovtun, M.E., Balakireva, M., McLachlan, I.G., Camonis, J., and Schwarz, T.L. (2013) Ral mediates activity-dependent growth of postsynaptic membranes via recruitment of the exocyst.
EMBO J. 32: 2039-55.

Pekkurnaz, G., Trinidad, J.C., Wang, X., Kong, D. and Schwarz, T.L. (2014). Glucose Regulates Mitochondrial Motility via Milton Modification by O-GlcNAc Transferase.
Cell, scheduled for July 3 2014 issue.



© 2013 by the President and Fellows of Harvard College