Research & Discoveries
The Biochemistry of Primary Cilium in Neurodevelopment
The primary cilium is a non-motile cilium found on the surface of nearly every cell types. It functions primarily as an “antenna’’ on the cell membrane to capture and transduce signals from extracellular signaling molecules to the cytoplasm and nucleus. We aim to decipher the molecular machineries underlying the biogenesis and signal transduction in the primary cilium, particularly, in the context of neurochemistry and neurobiology.
Human Stem Cell & Disease Modelling of Ciliopathy and Neurological Disorders
Impairment of the primary cilia adversely affects the physiological functions of multiple organs including the brain. In children, defective primary cÂÂÂilia lead to a class of heritable disorders collectively known as ciliopathies. We use CRISPR/Cas9 genome editing and induced-pluripotent stem cells (iPSC) technologies to establish the disease models of congenital diseases such as ciliopathies in animal and cellular platforms. Using these disease models in combination with biochemistry assays, comparative proteomics and genomics approaches, we aim to study the disease mechanism of ciliopathies; as well as to develop new therapeutics targeting ciliopathies.
Neurometabolsim
Emerging clinical evidence reveal that ciliopathy patients often manifest metabolic disorders, suggesting causal relationship between primary cilium and hormonal response in energy homeostasis. Using genetically-modified mouse models and human stem cells as the research platforms, we decipher the subcellular and genetic basis underlying neurometabolism homeostasis in the central and peripheral nervous systems.