Our research is focused on the molecular mechanisms of the following three cellular processes in health, and protein engineering for treating related diseases:

1. Actin-Based Cell Motility

Actin participates in many cell motile events in both health (e.g., muscle contraction, cell migration, cell division, cell shape maintenance) and disease (e.g., cardiomyopathy, cancer invasion, microbial pathogenesis).

Ongoing projects: red blood cell shape maintenance; nucleation of actin filaments by formins; interactions between the actin cytoskeleton and pathogenic proteins from Listeria, Plasmodium, and Borrelia.

2. Cytokinesis

Cytokinesis, the last step of cell division, is characterized by constriction of the actin-myosin contractile ring. During the division of one mother cell into two daughter cells, mutations in the cytokinesis proteins can cause severe problems (e.g., tumor and infertility). The final goal of this research is to recapitulate this process in vitro and to provide clues to correct or remove the mutations.

Ongoing projects: assembly and regulation of contractile ring by molecular machineries; disassembly of the contractile ring by oxidases.

3. Transmembrane Signaling

This process starts with the binding of an extracellular molecule to the integral membrane receptor. The subsequent transduction of this information across the cell membrane translates the extracellular binding event to one or more intracellular signals that alter the behavior of the target cell. Mutations in the extracellular molecule, the receptor, or intracellular binding proteins can cause abnormal signal transduction, which is quite common in tumors, leukemia, and developmental defect. Structure-based engineering of extracellular proteins combined with directed evolution is proven to be effective to alter the signaling, and targeted protein degradation can be used to remove the mutated proteins.

Ongoing projects: receptors for regulation of meiosis and mitosis in mammalian and yeast cells; receptors for neuronal development; receptors for immune responses.

The major methods employed in our lab are molecular cloning, protein expression (in bacterial, yeast, insect, and mammalian cells) and purification (from both cultured cells and natural sources), cryogenic electron microscopy (single-particle, helical reconstruction, and tomography), gene editing and yeast genetics/genomics, confocal fluorescence microscopy, structure-based and evolution-based protein engineering, and targeted protein degradation.