Research

Our group is interested in how collective cell behavior emerges and links with biological functions in development and reproduction. We focus on cellular mechano-chemical coupling regulations in mammalian tissues and explore design principles of multicellular dynamical systems.

We have studied how chemical cell signaling changes according to and regulates mechanical forces in multicellular tissues by combining fluorescence live-imaging and mathematical modeling. In particular, we used the FRET cell imaging technique to detect kinase activity and clarified that extracellular signal-regulated kinase (ERK) activity is mechano-sensitive and generates active cellular forces. These properties underpin collective epithelial migration (2020, Dev Cell; 2021, Nat Phys) and tissue morphogenesis in developing murine organs, such as tracheal and cochlear duct (2021, Front Cell Dev Biol; 2021, eLife). Moreover, we have proposed that the ERK-mediated mechano-chemical coupling depends on tissue curvature in the murine lung epithelium, which regulates recursive branching patterning (2024, Curr Biol). We will pursue this regulatory principle by integrating the 3D tissue geometry, to understand not only morphogenesis but also tissue homeostasis and repair.

Another aspect of our biological interest is reproduction. The origin and roles of germ cell dynamics in reproductive tracts remain less understood despite their physiological importance (2022, Semin Cell Dev Biol). To better understand, we have used intravital microscopy for studying murine reproductive tracts, enabling us to observe the cellular and molecular activities in living mouse tissues (2021, Biol Reprod; 2022, Reproduction). Particularly, we will explore the biophysical mechanisms of how collective sperm dynamics emerges and links with reproductive functions.

Key Methods

Fluorescence Imaging

We use various types of fluorescence microscopes, observation techniques, and fluorescence biosensors. Some typical examples are listed below. 

Mathematical modeling

As we choose a framework according to the purpose, we will work on any modeling style. We often employ phenomenological modeling using cell-scale agent-based frameworks and differential equation systems. We are also working on data-driven modeling using machine learning techniques. 

Research Topics

There are several themes listed below, but we do not have any particular preference for either the biological material, phenomenon, or method. Priority is given to the scientific curiosity of each individual. Rather than tackling 'popular' issues in a field where many people are competing, we would like to discover and set up intriguing problems and promote original research that can create new scientific values in the long run.

1) Multicellular Response to Force and Geometry

Cells have ingenious machinery to receive input stimuli from mechanical forces, stiffness, and shape of the surrounding environment and convert the signal into various cellular motions. The characteristic molecular and cellular dynamics that emerged from cell collectives, each of which exhibits such complex input-output responses, is a fundamental process of living systems that underlies biological functions. We focus on the property of cellular responses that actively generate force and deformation in response to the mechanical and topographical stimuli, and aim at elucidating the mechanisms of their collective systems (2020, Dev Cell; 2021, Nat Phys). We are also working on the development of measurement technologies that contribute to the life science field from the perspective of mechanobiology and biophysics.

2) Morphogenesis and Pattern Formation in Multicellular Tissue

In the natural world, simple patterns appear repeatedly. The internal organs in our body are no exception. For example, the lungs and kidneys branch out again and again like a tree. The cochlear duct of the inner ear forms a spiral like a snail. In the formation process of these patterns, simple morphogenetic ‘motifs’ are repeatedly used. We believe that the appearance of morphogenetic motifs in an appropriate spatio-temporal order is the key to understanding complex organ morphogenesis. So, how does a group of cells create the morphogenetic motifs as its basic unit? What are the regulatory systems that control the appearance of motifs? With these questions, we have the following research topics:

Through the basic studies, we would like to have a better understanding of organ morphogenesis, as well as contribute to the field of synthetic morphogenesis. Also, we will explore the design principles of pattern formation by comparing the organs’ pattern formation with non-living pattern formation phenomena.

3) Molecular and Cellular Dynamics in Reproductive Function

The origin and roles of sperm cell dynamics in the reproductive tracts remain less understood despite their physiological importance (2022, Semin Cell Dev Biol; 2023, Andrology). To better understand, we have utilized intravital microscopy for studying murine reproductive tracts, enabling us to observe the cellular and molecular activities in living mouse tissues. In this project, we will combine live cell imaging, microfluidic devices, and mathematical modelling to further explore the fundamental mechanisms of how collective sperm dynamics emerge and link to reproductive functions and aging.