Our primary goal is to unravel the molecular events that dictate the regenerative response of neurons in the peripheral nervous system and to relate this information to the lack of regenerative capacity in the central nervous system.
We also seek to understand how satellite glial cells, which wrap sensory neuron soma, contribute to sensory function and dysfunction in health and disease states. We explore their function in neurodevelopmental disorders and aging.
Permanent disabilities, including paralysis, numbness and pain following central nervous system (CNS) injuries, result from the failure of injured axons to regenerate and rebuild functional connections. The poor regenerative capacity of mature CNS neurons remains a major problem in neurobiology and an unmet medical need. There are currently no satisfactory treatments to restore mobility and sensation following spinal cord injury (SCI) or vision after optic nerve damage. In contrast, axon regeneration and partial functional recovery can occur in injured peripheral nerves, providing an opportunity to identify molecular mechanisms that control the axon regeneration program. However, recovery from a peripheral nerve injury is typically slow and often incomplete and depends on the severity of the injury. Therefore, there is a need to identify new treatments to maximize functional recovery after peripheral nerve injury.
To understand how to improve axon regeneration, our lab studies a unique cell type that spans both central and peripheral nervous systems: sensory neurons of the dorsal root ganglia. The cell bodies of sensory neurons reside in the dorsal root ganglion, a structure that sits just outside the spinal cord. These sensory neurons have a unique pseudo-unipolar morphology with a single axon that bifurcates within the ganglion. One axon proceeds along peripheral nerves. The other proceeds centrally along the dorsal root into the spinal cord. Importantly, the peripheral axon has a much greater regenerative capacity than the central axon.
The primary focus in the Cavalli Lab is to reveal the principles and mechanisms by which injured sensory neurons regenerate and elucidate the contribution of the neuronal microenvironment to axon growth and sensory function. Our goal is to identify potential targets for future treatment of CNS and severe nerve injuries.
We accomplish these goals using the mouse model system and apply a combination of biochemistry, cell biology, in vitro and in vivo imaging techniques, and behaviors and single cell sequencing approaches. Using human tissue, we also determine whether the findings made in the mouse model system are relevant to human physiology.
Current Projects
Intrinsic mechanisms controlling axon regeneration
We are studying the mechanisms by which a pro-regenerative state is reprogrammed following axon injury in sensory neurons.
Role of satellite glial cells and the DRG microenvironment in axon regeneration
We are using single-cell RNAseq of DRG in naïve and injured conditions in vivo to unravel if and how non-neuronal cells respond to injury and actively contribute to the axon regeneration process.
Role of satellite glial cells in neurodevelopmental disorders and aging
Satellite Glial Cells (SGCs), which closely envelop sensory neuron somas in the dorsal root ganglia (DRG), play a pivotal role in maintaining neuronal function and responding to environmental changes. We have expanded our studies to understand the contribution of SGCs to sensory dysfunction in mouse models of neurodevelopmental disorders (Fragile X syndrome) and in aging.
Targeted strategies to improve regeneration in the injured CNS
As we progress in deciphering the pathways regulating axon regeneration in peripheral sensory neurons, we are testing whether manipulating neurons and non-neuronal cells, genetically or pharmacologically, enhances axon regeneration in the CNS, using both the spinal cord and the optic nerve injury models.
Collaborators at Washington University
- Ram Dixit, Department of Biology
- Stefanie Geisler, Department of Neurology
- Rob Gereau, Department of Anesthesiology
- Vitaly Klyachko, Department of Cell Biology and Physiology
- Mayssa Mokalled, Department of Developmental Biology
- Clay Semenkovich, Division of Endocrinology, Metabolism & Lipid Research
- Guoyan Zhao, Department of Genetics