Wu Lab

Research Description

Significance of Studying Cytokinesis and Cellular Wound Healing

Two defining characteristics of cancers are uncontrolled cell division and metastasis. We are studying cellular processes that are related to both aspects of cancers in model systems using complementary approaches; including genetics, quantitative microscopic imaging, cell biology, biochemistry, and mathematical modeling. Cytokinesis, the final step of the cell-division cycle, is essential for cell proliferation and differentiation. Failure of cytokinesis can lead to tetraploidy, a prelude to aneuploidy and transformation of normal cells into cancer cells. Cancer cells often misregulate structural and regulatory components of cytokinesis. Since most proteins involved in cytokinesis are evolutionarily conserved, principles established in our model system of the fission yeast S. pombe can be readily applied to higher eukaryotes, including humans.

Cellular wound healing and cytokinesis are evolutionarily related processes due to both involving the actomyosin-cytoskeleton remodeling and plasma-membrane dynamics. Cellular wound healing is a ubiquitous process in eukaryotic cells and is essential for their survival. During metastasis, cancer cells are often stressed and wounded by the dense stroma and extracellular matrix. What we learn about molecular mechanisms of cellular wound healing will help us understand this intriguing biological process and design new or improved therapies to inhibit wound healing of cancer cells. Thus, our studies on cytokinesis and cellular wound healing will advance our understanding of basic fields significant to cancer research and human health.

Moreover, aspects of cytokinesis and cellular wound healing specific to fungi are excellent targets for anti-fungal drugs that have minimal impact on mammalian hosts. Approximately 1.2 billion people worldwide suffer from fungal diseases. Almost 2 million of them die of fungal infections every year. Inhibitors (caspofungin, micafungin, Aculeacin A, and others) of the conserved β-glucan synthases that build the septum for cytokinesis are used to treat fungal infections. However, anti-fungal drug development has largely stalled since the 1990s and drug resistance is rapidly emerging. Novel and basic knowledge of septum/cell wall synthesis is urgently needed. Therefore, discoveries on both conserved and organism-specific attributes of cytokinesis and cellular wound healing may be harnessed to improve human health.