Valeria Cavalli, Ph.D.

Associate Professor
Neuroscience
Hope Center for Neurological Disorders

Neurosciences Program
Molecular Cell Biology Program
Developmental, Regenerative and Stem Cell Biology Program
Biochemistry Program

  • 314-362-3540

  • 314 362 0155

  • 8108

  • 922 McDonnell Sciences Bldg

  • cavalli@wustl.edu

  • http://thalamus.wustl.edu/cavallilab

  • axon, regeneration, injury, epigenetic, membrane trafficking, cytoskeleton, degeneration, calcium, signaling

  • Cellular, Molecular and Epigenetic control of axon regeneration

Research Abstract:

Permanent disabilities following central nervous system (CNS) injuries result from the failure of injured axons to regenerate and re-build functional connections. The poor intrinsic regenerative capacity of mature CNS neurons is a major contributor to the regeneration failure and remains a major problem in neurobiology. In contrast to CNS neurons, peripheral sensory neurons successfully regenerate injured axons. However,
functional recovery in the peripheral nervous system (PNS) is often incomplete, especially after complete nerve transection or when axons need to re-grow long distances to reach their targets. Peripheral nerve injury can also result in chronic pain. The primary goal in the Cavalli lab is to reveal the principles and mechanisms by which injured sensory neurons re-activate a pro-regenerative program following axon injury and identify potential targets for future treatment of CNS injuries and severe PNS injuries. We use biochemical, molecular, cell biological, imaging, behavioral, genetic and epigenetic approaches in the mouse model system to elucidate the mechanisms controlling axon regeneration.


1. Retrograde injury signaling. We have focused on the issue of retrograde injury signaling, or how information about an injury is conveyed from the distantly located lesion site in the axon back to the cell body. We have discovered aspects of this mechanism that include the retrograde transport of organelles bearing the adaptor protein JIP3 on their surface and the role of the DLK/JNK signaling pathway in injury signaling and axon regeneration. We also recently explored the mechanisms initiating this retrograde transport and discovered that increased levels of tyrosinated α-tubulin at the injury site facilitates retrograde injury signaling and is required to activate a pro-regenerative program. We have also revealed that axon injury elicits a back-propagating calcium wave invading the soma and causing changes in the epigenetic landscape. We are following these studies to uncover the detailed mechanisms controlling axon to soma communication following neuronal injury.

2. Epigenetic and translational regulation of axon regeneration. We are studying the mechanisms by which a pro-regenerative state is reprogrammed following axon injury. Recently, we demonstrated that axon injury elicits an epigenetic switch controlling regenerative competence in sensory neurons. Our studies revealed that axon injury elicits the nuclear export of the histone deacetylases HDAC5, leading to enhanced histone acetylation and activation of a pro-regenerative transcriptional program. Moreover, this study reveals critical differences in epigenetic responses of peripheral and central neurons, and may be transformative in our understanding and approaches to treatment of nerve injuries. Given that epigenetic regulations affects globally, yet specifically, an ensemble of genes, they represents ideal strategies to promote neural repair. We are pursuing our studies to uncover the epigenetic, transcriptional and translational pathways that are induced by axon injury and culminate in the activation of a pro-regenerative program.

3. Microtubule modifications and molecular motors in axon growth and regeneration. Our research also focuses on the microtubule tracks on which injury signals are transported along axons and the role of microtubule post-translational modifications in injured axons. These studies led us to discover that injury to peripheral, but not central neurons induces microtubule post-translational modifications. These modifications are critical for growth cone dynamics and axon regeneration. These findings point to the important roles of microtubule post-translational modifications in the ability of injured axons to regenerate. We have are also studying the role of molecular motors in injury signaling and anterograde transport, particularly the mechanisms that regulate and coordinate molecular motor activity and directionality. We have shown that the motor adaptor JIP3, which is essential for retrograde injury signaling, also functions as a positive regulator of kinesin-1 motility, controlling axon growth in developing neurons as well as axon regeneration.

Selected Publications:

Cho Y, Park D and Cavalli V (2015) Filamin A is required in injured axons for HDAC5 activity and axon
regeneration. J. Biol. Chem, Jul 8. pii: jbc.M115.638445. [Epub ahead of print]

Watt D, Dixit R and Cavalli V. (2015) JIP3 activates kinesin-1 motility to promote axon elongation.
J. Biol. Chem. 290(25):15512-25.

Song W, Cho Y, Watt D and Cavalli, V. (2015) Tubulin-tyrosine ligase (TTL)-mediated increase in tyrosinated α-tubulin in injured axons is required for retrograde injury signaling and axon regeneration.
J Biol Chem. 290(23):14765-75

Cho Y*, DiLiberto V*, Carlin D, Li KH, Guan S, Michaelevski I, Abe N, Burlingame A, Cavalli V (2014). Syntaxin13 expression is regulated by mammalian Target Of Rapamycin (mTOR) in injured neurons to promote axon regeneration. J. Biol. Chem. 289 (22);15820–15832

Cho Y and Cavalli V (2014) HDAC signaling in neuronal development and regeneration. Curr Opin Neurobiol. 27: 188-126.

Cho Y, Sloutsky R, Naegle KM and Cavalli V (2013). Injury-induced HDAC5 nuclear export is essential for axon regeneration. Cell, 155, 894-908. Highlighted article

Cho Y and Cavalli V. (2012) HDAC5 is a novel injury-regulated tubulin deacetylase controlling axon regeneration. EMBO Journal, 31:3063-78. Highlighted article

Sun F, Zhu Z, Dixit R and Cavalli V. (2011) Sunday Driver /JIP3 binds kinesin heavy chain directly and enhances its motility. EMBO Journal. 30:3416-29

Abe N, Borson SH, Gambello MJ, Wang F and Cavalli V.(2010). Mammalian Target of Rapamycin (mTOR) activation increases axonal growth capacity of injured peripheral nerves J Biol Chem. 285:28034-43.

Abe N and Cavalli V. Nerve injury signaling. Curr Opin Neurobiol. 2008 18:1-8.

Last Updated: 9/28/2015 10:38:24 AM

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