William Maul Measey Professor of Physiology
Perelman School of Medicine
University of Pennsylvania, Philadelphia
The Holzbaur lab is focused on understanding the dynamics of organelle motility along the cellular cytoskeleton, driven by the molecular motors cytoplasmic dynein and kinesin. The active transport of membrane-bound organelles is required for intracellular biosynthetic, endocytic, and degradative trafficking in most eukaryotic cells. However, the highly polarized morphology of neurons, with axons that can extend over distances of up to one meter, make these cells uniquely dependent on motor-driven transport. Defects in this transport are sufficient to cause neurodevelopmental and/or neurodegenerative disease. The lab is identifying the underlying cellular mechanisms regulating intracellular transport in neurons, and how defects in trafficking contribute to diseases including ALS, Huntington’s disease and Parkinson’s disease. Pathways currently a major focus of study in the group include autophagy and mitophagy. They are investigating mechanisms of autophagosome biogenesis, cargo capture, organelle dynamics, and cargo degradation, and how these mechanisms are affected by aging and implicated in neurodegenerative disease.
Expression of WIPI2B counteracts age-related decline in autophagosome biogenesis in neurons.
eLife, 16;8. pii: e44219. doi: 10.7554/eLife.44219.
Stavoe AKH, Gopal PP, Gubas A, Tooze SA, Holzbaur ELF (2019)
Compartment-specific regulation of autophagy in primary neurons.
Journal of Neuroscience 36(22) 5933-5945. doi: 10.1523/JNEUROSCI.4401-15.2016.
Maday, S, and Holzbaur, ELF (2016)
Dynamic recruitment and activation of ALS-associated TBK1 with its target optineurin are required for efficient mitophagy.
Proceedings of the National Academy of Sciences 14;113(24):E3349-58. doi: 10.1073/pnas.1523810113
Moore, AS, and Holzbaur, ELF (2016)
Quality control in neurons: mitophagy and other selective autophagy mechanisms.
Journal of Molecular Biology, in press pii: S0022-2836(19)30428-0. doi: 10.1016/j.jmb.2019.06.031
Evans, CS, Holzbaur ELF (2019)
Vesicular degradation pathways in neurons: at the crossroads of autophagy and endo-lysosomal degradation.
Current Opinion in Neurobiology 57:94-101. doi: 10.1016/j.conb.2019.01.005.
Boecker CA, Holzbaur EL (2019)
Axonal autophagy: Mini-review for autophagy in the CNS.
Neuroscience Letters 697:17-23. doi: 10.1016/j.neulet.2018.03.025.
Stavoe AKH, Holzbaur ELF (2018)