Dong Yan, PhD
364 CARL Building
Box 3054 DUMC
Durham, N.C. 27710
Phone: (919) 684-1929
Our research focuses on understanding the molecular mechanisms underlying neural circuit formation during development and degeneration in aging. We use a free-living tiny roundworm, called Caenorhabditis elegans, as a model. The defined cell lineage, completely mapped connectome and rapid life cycle of this organism greatly facilitate investigating nervous system at the subcellular resolution. Combining classic genetic analysis with in vivo live imaging technique and molecular and cellular manipulations, we are discovering conserved mechanisms playing key roles in neural circuit formation, gap junction regulations and neurodegeneration.
Neural circuit formation: The development of C. elegans nervous system resembles some critical steps of mammalian cortex development. We use a simple motor neural circuit, RME circuit, as a model to investigate the conserved mechanisms of neural circuit formation. Four RME neurons are generated at the surface of embryos, and then migrate toward the center of embryos. After arriving at the pharynx region, RME left and right neurons adjust their positions to align four RME neurons with the same distance. RME neurons also undergo axon/dendrite development and synapse formation to build the connections between neurons. Through studying the RME circuit, we are uncovering novel mechanisms regulating neuronal migration, axon/dendrite differentiation and synapse elimination.
Neurodegeneration: Aging-related neurodegenerative diseases have become the hottest topics in the medical field. However, 99.6% of the drug development clinical trials for those diseases during the past decade have ended in failure. It seems that we need to rethink about the influential factors affecting the onset of these diseases. Aging, which is natural to all of us, is the most obvious one of them. However, it remains unclear what cause neurodegeneration during aging. We are using a sensitized genetic background to uncover negative and positive regulators of neurodegeneration.
Gap junction regulations: The nervous system is made by individual neurons connected by junction structures called synapses. There are two fundamentally different types of synapses: chemical synapses and electrical synapses (also called gap junctions). Through studies in different model organisms, we have gained rich knowledge of the development and regulation of chemical synapses. However, we still know little about how gap junctions are build during development, and what regulates the dynamic of gap junctions in functional circuits. We are investigating the molecular mechanisms underlying gap junction formation and regulations in C. elegans.