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Shasta Sabo

​​​​​Photo of Elizabeth W. AlmAssociate Professor
Biology​ 
Biosciences 4108
989-774-2342
Email sabo1s​@cmich.edu​
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Education​​
  • Research Associate, Stanford University, 2005-2007
  • Postdoctoral Fellow, University of California, Davis, 2001-2005
  • Postdoctoral Fellow, University of California, San Diego, 2000-2001
  • Ph.D., Rockefeller University, 2000
  • B.A., Integrated Science and B.A., Biological Sciences, 1994
​​​Research Interests
Neuroscience; Molecular and cellular mechanisms of synapse formation and neuronal development; Pathogenesis of neurodevelopmental disorders, such as autism spectrum disorders; Live fluorescence imaging 
​​​Current Research Projects
The neural circuits that govern perception and behavior are composed of networks of neurons that communicate with one another via synapses. As our brains develop, the roughly 10-20 billion neurons that comprise the human cerebral cortex are presented with the enormous and complex task of forming trillions of synapses with appropriate partners. Defects in synaptic connectivity and neural circuit development have been linked to diseases as diverse as anxiety disorders, depression, epilepsy, amblyopia, schizophrenia, intellectual disability and autism.

The overall goal of my lab's research is to understand (1) mechanisms of formation of neural circuits that are essential for perception and behavior, and (2) how perturbations in neuronal development, especially those related to neurodevelopmental and psychiatric disorders, affect the composition and function of neural circuits.

Our primary approach is to use fluorescence imaging, often in living neurons, to study development of synapses and neurons in real-time. Time-lapse imaging is powerful since it allows us to simultaneously study spatial and temporal aspects of development. We complement our imaging with molecular genetics and pharmacological tools, in order to manipulate the expression and function of individual proteins and neuronal activity during development.

Specific Projects:

1.    Understanding the cell-autonomous roles of neurotransmitter signaling in regulation of presynaptic development. Our previous work showed that presynaptic terminal development is facilitated by activation of NMDA receptors, and we now have evidence suggesting that this regulation is mediated by presynaptic NMDA receptors. We are interested in understanding more generally how presynaptic autoreceptors regulate presynaptic development and whether this regulation occurs at the level of individual synapses.

2.    Understanding how de novo autism-associated mutations affect neuronal development and contribute pathogenesis of simplex autism spectrum disorders. The biological causes of simplex ASD, with only one afflicted child per family, remain poorly understood. Recent genetic analyses have identified mutations that are unique to individuals with ASD, but whether and how these mutations lead to abnormal development is not yet known. Therefore, we are reproducing these mutations in rodent neurons and evaluating their effects on neuronal development.

3.    We are also working to identify signals that promote synapse formation in the hope that they will provide novel therapeutic targets for treatment of diseases that are characterized by synaptic loss, such as Alzheimer's Disease and depression.

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​​​​Selected Publications
  • Sabo SL, Lanier L, Ikin AF, Khorkova O, Sahasrabudhe S, Greengard P, Buxbaum JD. Regulation of beta-Amyloid Secretion by FE65, an Amyloid Protein Precursor-Binding Protein. Journal of Biological Chemistry. 274(12): 7952-7957. 1999.
  • Sabo SL, Ikin AF, Buxbaum JD, Greengard P. The Alzheimer Amyloid Precursor Protein and FE65, an APP-binding protein, Regulate Cell Movement. The Journal of Cell Biology. 153: 1403-1414. 2001. PMCID: PMC2150733.
  • Sabo SL, Ikin AF, Buxbaum JD, Greengard P. The Amyloid Precursor Protein and its Regulatory Protein, FE65, in growth cones and nerve terminals in vitro and in vivo. The Journal of Neuroscience. 23(13): 5407-5415. 2003.
  • Sabo SL and McAllister AK. Mobility and Cycling of Synaptic Protein-Containing Vesicles in Axonal Growth Cone Filopodia. Nature Neuroscience. 6(12): 1264-9. 2003.
  • Sabo SL and Sceniak MP. Somatostatin diversity in the Inhibitory Population. The Journal of Neuroscience. 26(29): 7545-7546. 2006.
  • Sabo SL, Gomes PR and McAllister AK. Formation of Presynaptic Terminals at Predefined Sites Along Axons. The Journal of Neuroscience. Oct 18; 26(42):10813-10825. 2006.
  • Gomes PR, Hampton CA, El-Sabeawy F, Sabo SL, McAllister AK. The Dynamic Localization of TrkB Receptors Before, During and After Synapse Formation. The Journal of Neuroscience.  26(44): 11487-11500. 2006.
  • Ikin AF, Sabo SL, Lanier LM, Buxbaum JD. A Macromolecular Complex Involving the Amyloid Precursor Protein (APP) and the Cytosolic Adapter FE65 is a Negative Regulator of Axon Branching. Molecular and Cellular Neuroscience. 35(1): 57-63. 2007.
  • Sceniak MP and Sabo SL. Modulation of firing rate by background synaptic noise statistics in rat visual cortical neurons. Journal of Neurophysiology. 104(5): 2792-805. 2010.
  • Bury LAD and Sabo SL. Coordinated Trafficking of Synaptic Vesicle and Active Zone Proteins Prior to Synapse Formation. Neural Development. 6:24. 2011.
  • Sceniak MP, Berry CT, Sabo SL. Facilitation of neocortical presynaptic terminal development by NMDA receptor activation. Neural Development. 7:8. 2012.
  • Berry CT, Sceniak MP, Zhou L, Sabo SL. Developmental up-regulation of vesicular glutamate transporter-1 promotes neocortical presynaptic terminal development. PLoS One. 7(11): e50911. 2012.
  • Bury LAD and Sabo SL. Dynamic Mechanisms of Neuroligin-Dependent Presynaptic Terminal Assembly in Living Cortical Neurons. Neural Development. 9(1): 13. 2014.
  • Gill I, Droubi S, Giovedi S, Fedder K, Bury LAD, Sceniak MP, Benfenati F and Sabo SL. Presynaptic NMDA Receptors: Dynamics and Distribution in Developing Axons in vitro and in vivo. Journal of Cell Science. 128(4): 768-80. 2015.
  • Bury LAD and Sabo SL. Building a Terminal: Mechanisms of Presynaptic Development in the CNS. The Neuroscientist.  2015.
  • Fedder KN and Sabo SL.  On the Role of Glutamate in Presynaptic Development: Possible Contributions of Presynaptic NMDA Receptors. Biomolecules. 5(4):3448-66. Dec 2015.