Ghazaleh Ashrafi, Ph.D.

Assistant Professor
Cell Biology and Physiology

Neurosciences Program
Molecular Cell Biology Program

  • ghazaleh@wustl.edu

  • Uncovering novel regulators of glycolytic and mitochondrial metabolism at the synapse and their role in the pathology of Alzheimer’s disease

Research Abstract:

The brain is the most energy consuming organ of the body and is highly sensitive to energetic perturbations. However, regulatory mechanism that modulate neuronal metabolism are poorly understood. In firing nerve terminals, both glycolysis and oxidative phosphorylation (OxPhos) are rapidly upregulated to meet the energetic requirements of synaptic activity1. While this upregulation represents transient modulation of neuronal metabolism, it is not clear how neurons adapt to chronic changes in energetic burden that also occur in neurodegenerative diseases such as Alzheimer’s disease (AD). The research in my lab will be focused on uncovering novel regulators of glycolytic and mitochondrial metabolism at the synapse and their role in the pathology of Alzheimer’s disease.

Selected Publications:

1. *Ashrafi, G., *de Juan-Sanz, J. Farrell, R. J., and Ryan, T.A. Molecular tuning of the axonal mitochondrial
Ca2+ uniporter ensures metabolic flexibility of neurotransmission. BioRxiv 685859. *equal contribution

2. Koopmans, F.,…, Ashrafi, G.,…, Verhage, M. (2019) SynGO: An Evidence-Based, Expert-Curated
Knowledge Base for the Synapse. Neuron 103: 1-18.

3. Ashrafi, G., and Ryan, T.A. (2017) Glucose metabolism in nerve terminals. Curr. Opin. Neurobiol. 45:156-
161.

4. Ashrafi, G., Wu, J., Farrell, R.J., and T.A. Ryan. (2017) GLUT4 mobilization supports energetic demands of
active synapses. Neuron 93: 606-615.
Highlight: Silm K, Edwards RH. (2017) One Cycle Fuels Another: The Energetics of Neurotransmitter
Release. Neuron 93:470-472.

5. Cao, M., Wu, Y., Ashrafi, G., McCartney, A.J., Wheeler, H., Bushong, E.A., Boassa, D., Ellisman, M.H.,
Ryan, T.A., and De Camilli. P. (2017) Parkinson Sac domain mutation in Synaptojanin 1 impairs clathrin
uncoating at synapses and triggers dystrophic changes in dopaminergic axons. Neuron 93: 882-896.

6. Ashrafi, G., and Schwarz, T.L. (2015) PINK1- and Parkin-mediated local mitophagy in distal neuronal axons.
Autophagy 11:187-9.

Last Updated: 12/15/2019 1:33:20 PM

Back To Top

Follow us: