Clarence S. Chan

Chan lab research is focused on two basic processes that are critical for the proliferation and well being of all eukaryotic cells — chromosome segregation (i.e., mitosis) and the spatial control of cell growth and function (i.e., cell polarity). Defects in either process are known to result in many forms of human cancer.

Using the budding yeast S. cerevisiae as a model system and a combination of molecular genetic, cell biological and biochemical methods, they study the roles of the conserved Aurora/Ipl1 protein kinase complex and the Cdc42 GTPase in the control of these two processes. The Aurora/Ipl1 protein kinase regulates diverse processes during mitosis, including kinetochore-microtubule attachment, cell cycle checkpoint control, mitotic spindle stabilization and cytokinesis. The function of Aurora/Ipl1 is counteracted by that of protein phosphatase 1 (PP1).

The lab is studying the functional relationship between PP1 and Aurora/Ipl1; the proteins that are phosphorylated and thus regulated by Aurora/Ipl1; and additional proteins that regulate Aurora/Ipl1 function. The genes encoding subunits of the human Aurora/Ipl1 kinase complex are commonly de-regulated in a variety of human cancer, and pharmacological agents that inhibit Aurora function suppress tumorigenesis in mouse model systems.

Thus, their study of the yeast Aurora/Ipl1 complex likely will contribute to ongoing efforts to control human cancer. The Cdc42 GTPase plays a central role in regulating cell polarity in diverse organisms. When GTP-bound, Cdc42 binds to specific effector proteins that include Gic1 and Gic2 in yeast. These effector proteins in turn regulate the organization of the actin cytoskeleton and other cellular processes. They are studying how effectors such as Gic1 and Gic2 help to organize the actin cytoskeleton and what other protein may functionally interact with Gic1 and Gic2 in yeast.