The lab focuses on studying the mechanisms of neuronal pruning using the model organism Drosophila melanogaster, or the fruit fly. Fruit fly has been well established to study many evolutionarily conserved biological pathways (largely conserved in humans) due to the availability of numerous genetic tools and minimal genetic redundancy. Fruit flies undergo neuronal pruning in response to ecdysone steroid hormone during metamorphosis, which strikingly resembles the synapse elimination process in human brains during adolescence.

The lab has established ddaC sensory neuron as an attractive in vivo model to systematically unravel the molecular and cellular mechanisms of dendrite pruning, by using a combination of molecular, genetic, biochemical, bioimaging and proteomics approaches. They have identified over 30 novel pruning factors and important pathways that initiate and execute pruning in sensory neurons. Those pruning genes and pathways are highly conserved in humans, raising the possibility that the pruning machinery identified from fruit flies might be also utilized during neuronal pruning in human brains. The steroid hormone-mediated pathways and epigenetic regulators, such Sox14, Mical, Brahma and CBP-related orthologs in humans, might be important for the pruning and maturation of nervous systems during human adolescence.

Looking ahead, the lab has initiated new research programmes with local clinician scientists by establishing human brain organoid culture facility in TLL. They aim to apply the knowledge on neuronal pruning gathered from flies to brain cortex development in humans. It is conceivable that some pruning machineries are conserved during human brain development and remodelling. In this regard, Dr Yu’s research will pave the way for future studies of those pruning genes in the context of neurodevelopment and neuro-pruning, as well as neurological disorders in humans. His research will develop translatable knowledge that potentially leads to the treatment of human neurodevelopmental disorders.