Valeria Cavalli Research Abstract
We are using sensory neurons with cell body in dorsal root ganglia (DRG), one of the most useful mammalian models to study axon regeneration. Sensory neurons have a unique pseudo-unipolar morphology with a single axon which bifurcates within the ganglion; one axon proceeds centrally along the dorsal root into the spinal cord and the other proceeds along peripheral nerves. Importantly, the peripheral axon has a much greater regenerative capacity than the central axon. 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. We use biochemical, molecular, cell biological, imaging, behavioral, genetic and epigenetic approaches in the mouse model system to elucidate the mechanisms controlling axon regeneration. We also use human tissue to determine if our findings in the mouse model system are relevant to the physiology of human neurons.
1. Epigenetic and transcriptional regulation of axon regeneration. To study the mechanisms by which a pro-regenerative state is reprogrammed following axon injury in neurons, we employ several approaches, including phenotypic genetic and drug screens combined with RNAseq and ATACseq in defined neuronal populations.
2. Neuronal extrinsic contributions to nerve repair. To unravel how other cells residing in dorsal root ganglia, such as satellite glial cells, macrophages and endothelial cells, contribute to the nerve repair process, we are using single-cell RNAseq of DRG in naïve and injured conditions.
3. Strategies to enhance axon regeneration in the injured central nervous system. As we make progress in deciphering the molecular and cellular pathways regulating axon regeneration in peripheral neurons, we are testing if corresponding manipulations enhance axon regeneration in the CNS. We are using both the spinal cord and the optic nerve injury models.
4. Role of the microtubule cytoskeleton in axon regeneration. We are studying how signaling pathways elicited by injury in axons regulate microtubule posttranslational modifications and the precise role these modifications play in injured axons.