Yang Hu, MD, PhD
Assistant Professor, Shriners Hospitals Pediatric Research Center
Telephone: 215-926-9358 (Internal: 7-9358)
Shriners Hospitals Pediatric Research Center
Department of Neuroscience
We are interested in axon regeneration and neuroprotection in central nervous system (CNS) after neural injury. Injuries of CNS axons often result in permanent loss of vital functions, such as loss of vision in multiple sclerosis and glaucoma and paralysis in spinal cord injury. This occurs because the axons in the adult mammalian CNS do not regenerate and injury-induced neural cell death. The ultimate goal of my laboratory is to develop efficient therapeutic strategies to achieve neural repair and functional recovery based on the fully understanding of the molecular mechanisms of neurodegeneration and CNS axon regeneration failure.
Previously we showed that the activation of the mTOR pathway by genetically deleting PTEN, can promote axon regeneration in adult retinal ganglion cells (RGCs) using optic nerve injury mouse model. The dramatic down-regulation of mTOR activity in mature neurons after axotomy may partly explain why regeneration is so poor in adult CNS. Our current focus is to extend these initial findings by exploring the mechanistic involvement of the PTEN/mTOR pathway in axon regeneration and functional consequences of regenerating optic nerve fibers after injury.
In addition to stimulate axon regeneration, another key aspect for neural repair is to promote neuronal survival. Our studies indicate that axon injury-induced ER stress plays a critical role in neurodegeneration. We are investigating the mechanisms of ER stress activation and exploring therapeutic means to manipulate signal transduction pathways downstream of ER stress to promote neuronal survival and functional recovery using glaucoma mouse model.