Faculty Research: Guofa Liu
Professor
Office: WO4268B |
Research
The human brain possesses approximately 1011 neurons and 1014 synapses forming an extraordinarily complex and highly precise network. The formation of proper neural circuitry relies on appropriate neuronal migration, axon guidance and synapse formation during neural development and following injury. Defects in axon guidance and neuronal migration are implicated in a variety of brain disorders, such as lissencephaly, double cortex, periventricular heterotopia, epilepsy, autism, schizophrenia, dyslexia, Alzheimer’s disease, Parkinson’s disease, stroke, traumatic brain injury and spinal cord injury. We are interested in studying the molecular mechanisms underlying neuronal guidance with a goal of providing better therapeutic interventions for central nervous system (CNS) disorders such as stroke and spinal cord injury.
Our research interests lie in three areas:
Intracellular signal transduction cascades mediating neuronal guidance. Coordination of different guidance cues, their receptors and intracellular signal
transduction cascades is crucial for neurons to find their targets and establish distinct
neuronal circuits. Netrin-1 is a prototypical guidance cue for projecting axons and
migrating neurons. We are currently untangling: 1) the collaboration of different
Netrin receptors in axon elongation, branching and guidance; 2) the coordination of
downstream signaling cascades of Netrin receptors; 3) the coordination of Netrins
with other guidance cues, such as Semaphorins, Slits and ephrins, in the developing
nervous system.
Cytoskeletal modulation in neuronal guidance. Modulation of actin and microtubule (MT) dynamics in the growth cone of neurons plays a crucial role in axon guidance and neuronal migration. However, whether MT dynamics is directly or directly involved in these processes is unclear. Our recent studies have suggested a novel working model that guidance receptors directly couple MT dynamics in neuronal guidance. We are currently investigating how guidance cues modulate MT dynamics through coupling of their receptors with MT subunits in attractive and repulsive signaling.
Axon outgrowth and regeneration. Axon regeneration is essential for re-establishing neural circuitry and recovery of nerve functionality after injury. The intrinsic ability for axon regeneration in the mature mammalian CNS after injury is extremely limited. An understanding of signal transduction cascades downstream of guidance cues will help us to design promising therapeutic strategies to promote axon regeneration and rescue defects in axon guidance and neuronal migration after CNS injury. Multiple signal transduction cascades have been found involved in promoting axon outgrowth, branching and neuronal migration. We are interested in identifying key players in these pathways in order to provide new treatment strategies for restoring neural function after CNS injury.