The primary interest of my laboratory is to elucidate the molecular mechanisms that drive and direct axon growth and regeneration during early development and especially after injury or degenerative disease. We make extensive use of genetically modified mice to model disease conditions and to manipulate axon growth-related signaling cascades in vivo.
Signaling pathways controlling axon growth and regeneration
In mammalian embryos, axons grow vigorously and precisely to interconnect the nervous system, and form connections to sensory receptors and muscles. In the mature nervous system, axon growth stops to maintain stability. After an injury, axons can regenerate, if imperfectly, in the peripheral nervous system, but no productive regeneration occurs in the central nervous system. Therefore, spinal cord injuries result in permanent paralysis, and retinal axon degeneration in glaucoma causes irreversible loss of vision, to name just two examples.
The goal of our research is to enable axon regeneration in the injured central nervous system, using experimental models of spinal cord injury and glaucoma. Several lines of genetically modified mice allow us to selectively activate or inactivate specific signaling molecules in neurons of interest in vivo. We assess regeneration phenotypes using high-resolution imaging, and we test for possible recovery of motor or visual behaviors.
Mapping Neuronal Circuits
We are developing a reporter mouse that will express a novel transsynaptic tracer. In these mice we will be able to visualize the entire network of neurons connected to an initial neuron (or a group of neurons) of interest, and to manipulate gene expression in these neurons. This model will be useful for a number of purposes, for example to delineate neuropathic pain circuitry, or to document axon rewiring in a regeneration context.
Develop new treatment options for the RASopathies in mouse models
The RASopathies (also referred to as neuro-cardio-facio-cutaneous syndromes) are a related group of complex neurodevelopmental disorders affecting up to 1 in1000 live births. Mutations affecting the RAS–RAF–MAP kinase signaling pathway have been causally linked to the RASopathies. We have developed several mouse models which mimic the neurological aspects of human RASopathies' syndromes. We utilize these mice to investigate the underlying pathological causes of devise symptoms and test possible therapeutic strategies.
Dr. Zhong is the Director of the Molecular Regeneration and Imaging Laboratory at the Burke Medical Research Institute and the Director of the Burke Center for Pain and Sensory Recovery.