We use modern molecular, cellular and biochemical techniques as well as bioinformatics and systems biology tools to study the roles of genes and pathways in development and disease. Techniques we are currently using include CRISPR/Cas9 genome editing, single-cell RNA-seq and spatial transcriptomics, label-free and tandem mass tag-based proteomics, integrative multi-omics analysis, high-resolution imaging, and drug screens using robotics and DNA-encoded libraries.
Project 1. The mechanisms of neural crest development and craniofacial birth defects. The neural crest cells are multipotent stem cells that give rise to craniofacial structures, cardiac tissues, pigment cells, the peripheral nervous system, and many other derivatives. Aberrant neural crest development can lead to craniofacial disorders (such as cleft lip and palate) and other birth defects in humans. Using frogs, mice and cultured mammalian cells, we are investigating the roles of genes and signaling pathways, including the AKT, MAPK and canonical Wnt pathways, in neural crest development under normal and pathological conditions. We are particularly interested in understanding the pathophysiology of human craniofacial disorders caused by genetic mutations.
Project 2. Function and regulation of canonical Wnt signaling. The canonical Wnt pathway plays important roles in development and disease, including neuronal development, carcinogenesis, and tumor progression. Both the inputs and outputs of Wnt signaling are regulated by many genes through various mechanisms, and perturbation of any of these regulatory mechanisms may lead to diseases. A major focus of our research is on identifying novel upstream regulators and downstream effectors of Wnt signaling and understanding their functions in normal and pathological processes.
Project 3. The biochemistry and cell biology of extracellular metalloproteinases. Extracellular metalloproteinases, such as disintegrin metalloproteinases (ADAMs) and matrix metalloproteinases (MMPs), are key regulators of cell signaling and tissue homeostasis. Abnormal ADAM/MMP activities are often associated with pathological processes such as tumor progression, cartilage degradation (as in arthritis), neurodegenerative diseases, and COVID-19. We are interested in understanding how the expression, maturation and activities of these metalloproteinases are controlled, as well as identifying novel ADAM/MMP substrates using both candidate and nonbiased (proteomics) approaches. Finally, we are collaborating with several other labs to identify new ADAM/MMP inhibitors for research and therapeutic purposes.