Damage to the adult CNS, such as spinal cord injury (SCI) often leads to persistent deficits due to the inability of mature axons to regenerate after injury. Under pathological situations such as multiple sclerosis (MS), the second most common neurological disorder leading to disability in young adults, the failure of damaged axons to regenerate contributes to non-reversible neurologic dysfunction. Currently, only a few therapies with limited efficacy are available, highlighting the urgent need to identify novel molecular targets and develop targeted therapies. What is also lacking is a systematic way to dissect the pathways underlying the four steps of axon regeneration, namely degeneration/debris clearance, regrowth, overcoming the hostile environment and re-building connectivity.
Cross-species and multi-model analyses to map the gene circuits critical for maintaining nervous system function
Our lab builds on a platform to take advantages of the power of fly genetics in discovering novel factors together with the mammalian injury models to study their homologs and functional recovery. We have established the Drosophila sensory neuron degeneration and regeneration model, and have recently developed a second Drosophila CNS injury model. We and collaborators have been utilizing and generating fly brain tumor models. We have experience with the fly neurodegeneration model, the rodent optic nerve crush and spinal cord injury models. We further plan to adopt the rodent motor neuron degeneration, glaucoma and traumatic brain injury models. Thus we will use fly as a discovery tool, to identify genetic pathways important for neural degeneration, regeneration and tumorigenesis, and assess their evolutionary conservation in vertebrates.
Theme I: Identifying novel pathways regulating axon degeneration and regeneration
The RNA repair/splicing pathway in axon regeneration
Identifying downstream effectors of the RNA repair/splicing pathway in regulating axon regeneration
The mammalian optic nerve crush model for studying axon regeneration.
The mammalian spinal cord injury (SCI) model for studying axon regeneration.
Ongoing genetic screens for regulators of axon/dendrite degeneration/regeneration
Theme II: Linking pathways regulating regeneration and neurodegenerative diseases
Theme III: An integrative and comparative strategy to study regeneration and tumorigenesis
Theme IV: Regenerative medicine
Based in the Raymond G. Perelman Center for Cellular and Molecular Therapeutics (CCMT), which is dedicated to the understanding, development, and application of gene and related cell and nucleic acid therapies, a major translational goal of the lab is to develop therapeutic strategies utilizing the targets identified from our mechnistic studies, for treating patients with neural injury, stroke and neurodegenerative diseases.
Fun future research ideas: studying aggression and courtship in flies. New ideas welcome!
Potential Rotation Projects
1. Utilize the fly sensory neuron injury model to identify and characterize novel pathways regulating dendrite/axon degeneration and regeneration.
2. Establish new fly injury models
3. Study tumorigenesis in flies (brain tumors and others)
4. Fun Drosophila behaviors
5. Study degeneration and regeneration using mammalian injury models in vitro and in vivo