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Research Overview

The Schwarz Lab works at the intersection of neuroscience and cell biology. In the last decade, the mechanisms of axonal transport and the dynamics of mitochondria have become primary areas of interest and combine fundamental cell biology with insight into the etiology and treatment of neurodegenerative disorders. Our approach has been to use whatever system is most pertinent to the scientific question, from Drosophila genetics to rodent neurons, to patient-derived iPSCs. We combine advanced imaging methods, molecular biology, genetics, and pharmacology to reach our goal of a mechanistic understanding. One current focus is on neurodegenerative mechanisms and, in particular, how defects in mitochondrial transport and clearance contribute to neuropathology in Parkinson’s Disease and ALS. These studies complement our other projects on synapse formation and the cell biological processes that allow a growth cone to transform into a functional synaptic bouton.

Research Background

Selected Publications

  1. Chung J.Y., Steen J.A., Schwarz T.L. (2016) Phosphorylation-Induced Motor Shedding Is Required at Mitosis for Proper Distribution and Passive Inheritance of Mitochondria Cell Reports. 16(8):2142-55. doi: 10.1016/j.celrep.2016.07.055. Epub 2016 Aug 11.
  2. Ashrafi, G., Schlehe, J. S., LaVoie, M. J., & Schwarz, T. L. (2014). Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin. The Journal of Cell Biology, 206(5), 655–670.
  3. 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, 158:54-68. 
  4. 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.
  5. 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. 
  6. Mosca, T.J. and Schwarz, T.L. (2010) The nuclear import of Frizzled2-C by Importins beta11 and alpha2 promotes postsynaptic development.  Nat Neurosci. 66:624-7. 
  7. 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.
  8. Pack-Chung, E., Kurshan, P.T., Dickman, D.K., and Schwarz, T.L. (2007) A Drosophila Kinesin Required for Synaptic Bouton Formation and Synaptic Vesicle Transport.  Nature Neuroscience 10:980-989.
  9. Dickman, D.K, Horne, J.A., Meinertzhagen, I.A., and Schwarz, T.L.  (2005)  A slowed classical pathway rather than kiss-and-run mediates endocytosis at synapses lacking synaptojanin and endophilin.  Cell 123:521-533.

Publications