How the proliferation of cells, "Cell Cycle", coordinates with cellular differentiation to form and maintain functional tissue is one of the most fundamental questions of the biology of multicellular organisms.  Imbalance between these processes disrupts normal development of embryos and the homeostasis of adult tissue, and is also associated with various human diseases including cancer, fibrosis and neurodegenerative diseases.

We address this crucial question by exploiting powerful genetics of the multicellular model organism, Drosophila melanogaster (fruit fly), combined with cutting-edge in vivo imaging, biochemistry and multi-OMICs techniques.  Through our research we will uncover evolutionally conserved molecular mechanisms that integrate the cell cycle and cell differentiation in metazoan organisms. Furthermore, we also use human cell culture and mammalian organoids to translate our findings in flies into humans, with the ultimate goal of improving human health by our discoveries.

Roles of CCRs in cell fate decision and cell differentiation

Cell cycle regulators (CCRs) are a group of evolutionally conserved proteins that control the progression of the cell cycle. However, we and others recently found that, in multicellular organisms, some of these CCRs directly regulate cell fate decision and cell differentiation to couple these processes to the cell cycle control. We explore these novel metazoan-specific functions of CCRs in various tissues of Drosophila and examine their conserved roles in cultured human cells and tissues.

Mechanisms of cellular quiescence and cell cycle exit

A great majority of cells in the adult human body are either in a reversible dormant state (G0 phase), or have irreversibly exited from cell cycle. Using the Drosophila adult brain and gut as in vivo models, as well as in vitro culture of transformed and untransformed human cells, we investigate mechanisms that regulate the entry to and the exit from these cellular quiescent states. We also examine genetic and epigenetic changes that may occur in the genome DNA during these transitions and their long-term consequences on genome stability and tissue homeostasis.

Molecular interactions between CCRs and metazoan organelles

The centrosome and the cilium are interrelated membrane-less cell architectures that exit specifically in animal cells and control a wide variety of cellular events, such as cell migration, cell/tissue polarity and intracellular transport and signal transduction, through organisation of cytoskeletons. We investigate molecular crosstalk that happen between CCRs and components of these organelles and the roles of these interactions in cell cycle control, development and physiology, by using Drosophila tissues and human cell culture.