Research

Cytokinesis, Septin Assembly and Remodeling, Cell Polarity, and Epithelial Tube Formation

Research in our laboratory focuses on understanding the molecular mechanisms that govern cell organization and division. Using diverse experimental systems (yeast, mammalian cells, and mouse models), we combine genetics, advanced imaging, and biochemistry to investigate cytokinesis, septin assembly and remodeling, cell polarity, and epithelial tube formation.

Our cytokinesis research focuses on defining the architecture, dynamics, and regulation of the actomyosin ring (AMR), as well as how its function is coordinated with targeted vesicle fusion and extracellular matrix (ECM) remodeling at the division site. Our septin studies aim to uncover the principles governing septin higher-order assembly and remodeling during the cell cycle and how these processes contribute to successful cell division.

Another major area of research investigates how cytokinesis is coordinated with hepatocyte polarization and bile canaliculus (BC) formation and elongation—interconnected processes essential for liver architecture and function.

We are also developing the basidiomycetous yeast Kockovaella fuzhouensis as a new model system to explore fundamental and previously inaccessible questions in cell morphogenesis and division.

Keywords: Cytokinesis, abscission, actomyosin ring, exocytosis, ECM remodeling, septins, cell polarity, hepatocyte polarization, apical tube formation, cell morphogenesis

Research Areas

Cytokinesis

Cytokinesis in fungi and animal cells is achieved through the concerted actions of a contractile actomyosin ring (AMR), targeted vesicle fusion, and localized extracellular matrix (ECM) remodeling. Our goal is to determine:

how the AMR is assembled and disassembled during the cell cycle;
how the AMR is spatiotemporally coordinated with targeted vesicle fusion; and
how the sites of constriction flanking the midbody are generated to enable abscission.

We address these questions using both budding yeast and mammalian cells as model systems.

Cytokinesis in budding yeast and mammalian cells, showing septin and actomyosin ring dynamics, intercellular bridge formation, ESCRT recruitment, and abscission. — This figure is a two-panel scientific diagram comparing the stages of cytokinesis in **budding yeast** (left panel) and **mammalian cells** (right panel). Read more about Cyokinesis in Budding Yeast and Mammalian Cells.

Septin Assembly and Remodeling

Septins are cytoskeletal proteins that form rod-shaped heteromeric complexes, typically octamers, which polymerize into linear filaments and are further organized into higher-order structures such as rings and hourglasses. Septins play critical roles in diverse cellular processes, including cytokinesis, cell morphogenesis, and cell migration, by acting as scaffolds and/or diffusion barriers. We aim to understand: 1) how septins assemble into a ring or hourglass and how the hourglass is remodeled into a double ring at the onset of cytokinesis in budding yeast; 2) how septins undergo higher-order assembly and remodeling during furrow ingression and abscission in mammalian cells; and 3) how septin architecture and myosin-II are coordinated in time and space to execute cytokinesis in both yeast and mammalian cells.

Role of the LKB-1-like kinase Elm1 in septin hourglass assembly at the bud neck in budding yeast. — Role of Elm1 in Septin Hourglass Assembly in Budding Yeast

Roles of the RhoGEF (Bud3)-anillin (Bud4) module in the septin hourglass-to-double ring conversion in budding yeast. — Bud3 and Bud4 in Septin Hourglass-to-Double Ring Conversion in Budding Yeast

Hepatocyte Polarization and Bile Canaliculus Formation

The liver is a vital organ in vertebrates, responsible for essential functions such as detoxification and the synthesis and secretion of serum proteins and bile acids. These functions critically depend on the polarization of hepatocytes (liver cells)—specialized epithelial cells—and the formation of bile canaliculi (BC). Each BC is formed by the apical membranes of two adjacent hepatocytes and extends along rows of hepatocytes generated by oriented cell divisions, ultimately connecting to the bile duct. We previously discovered that cytokinesis defines a spatial landmark for hepatocyte polarization and BC formation. We are now investigating the molecular mechanisms underlying these processes using hepatocyte cell lines and mouse genetic models.

E- and N-cadherin regulate hepatic polarity and cytokinesis-linked bile canalicular elongation via opposing regulation of RhoA activity. — Model of Cadherin-Mediated Regulation of Hepatic Polarity and Bile Canaliculus Formation

Fluorescence microscopy of an E15.5 mouse embryonic liver section showing E-cadherin in green, N-cadherin in red, and ZO-1 in white at hepatocyte cell-cell junctions. Nuclei are shown in blue. — Cadherin and Tight Junction Protein Localization in an E15.5 Mouse Embryonic Liver

Developing a New Fungal Model to Explore Fundamental Questions in Biology

Millions of living organisms, spanning bacteria, archaea, fungi, animals, and plants, inhabit our biosphere, yet much of our understanding of biological systems is derived from studies of only a handful of model organisms. Expanding the repertoire of experimental models offers opportunities to uncover new biology and address existing questions from new perspectives and with greater efficiency. Because of its striking morphology and distinctive modes of polarized growth and division, we are developing the basidiomycetous yeast Kockovaella fuzhouensis as a new model system to address fundamental questions in cell and developmental biology.