RESEARCH

Nuclear Mechanobiology

Cell nucleus is a sophisticatedly structured organelle containing genetic information and is mechanically linked with the cytoskeletons through LINC complex. Maintaining the mechanical integrity of nucleus is an important task of the cell, and abnormal deformation of the nuclear architecture due to genetic defects or mechanical stress leads to cellular functional impairment. Our goal is to demonstrate how the physical regulation of nuclear structure induces various cellular regulatory processes including epigenetic modification, nuclear localization of transcription factors, and protein expression, emphasizing the importance of the nucleus-centered mechanical balance inside a mammalian cell.

Cell Mechanics & Mechano-regulation

The ability of cells to recognize, analyze, and respond to consistently changing extracellular substrate rigidity, termed mechanosensation, plays a crucial role in various physiological and pathological processes in vivo. For instance, the mechanical rigidity of the extracellular matrix seems to play an important regulatory factor during embryogenesis: mesenchymal stem cells grown on matrices of controlled stiffness mimicking brain tissue, striated muscle, and bone are differently differentiated towards neurogenic, myogenic, and osteogenic lineages, reflectively. We have developed a new platform to replace conventionally tested two dimensional mechanosensation assay and it will provide us a new insight on cellular mechanoregulations in a more in vivo relevant microenvironment.

Disease Biophysics

Biology studies life in its variety and complexity. It describes how organisms go about getting food, communicating, sensing the environment, and reproducing. On the other hand, physics looks for mathematical laws of nature and makes detailed predictions about the forces that drive idealized systems. Spanning the distance between the complexity of life and the simplicity of physical laws is the challenge of biophysics. Looking for the patterns in life and analyzing them with math and physics is a powerful way to gain insights. We use lenses of physical laws to solve the biological problems in a cellular and subcellular level. Particular interests also goes into the nuclear mechanics in diseased cells.

Single Molecular Biophysics

Various intracellular events involves development of forces such as actin polymerization, cell-ECM binding across transmembrane proteins, cytoskeletal tension in pulling and tugging cells. While these forces in subcellular level ranges from only a few pN to hundreds of nN, they govern fundamental biological functions, such as cell adhesion, migration, differentiation, embryogenesis, and even cancer metastasis.

We develop DNA-based single molecular force sensors to identify underlying mechanism of subcellular events, which will provide us the noble biophysical laws that connect single molecular biophysics and cell biology.

Digital Pathology

Digital pathology is a dynamic, image-based environment that enables the acquisition, management, and interpretation of pathology information generated from a digitalized glass slide. Digital pathology is rapidly gaining momentum as a proven and essential technology; with specific support for education, tissue based research, drug development, and the practice of human pathology throughout the world. It is an innovation committed to the reduction of laboratory expenses, an improvement of operational efficiency, enhanced productivity, and improving treatment decisions and patient care. We develop high-throughput cell phenotyping technique to identify the progression of diverse human diseases such as ischemic heart diseases and cancers.

Cell Reprogramming

Cell reprogramming is a biotechnology to convert mature cells from one lineage to another one that can be a source of patient-specific cells for regenerative medicine and drug discovery. Conventionally, indirect cell reprogramming has been utilized, where mature cells are converted to iPSC that will be further converted to target cell types. Direct cell reprogramming avoids intermediate steps that involves iPSC but directly converts mature cells into target cells with bypassing a pluripotent state. While various recipes have been developed by engineering chemical and genetic cues, biophysical cues are rarely studied in spite of its crucial role. We modulate essential physical cues during direct cell reprogramming, e.g., matrix stiffness, confinement, and topology to elucidate how cell reprogramming is regulated by intra-, extra- cellular biophysical cues.

Biologically Inspired Microfluidics

An organ-on-a-chip is a miniaturized multi-channel cell culture platform that simulates the activities, mechanics, and physiological response of organ system. While traditional in vitro cell culture and animal models are subject to insufficient in vivo condition, human relevance, ethical issues, recently developed organ-on-a-chip platform combining microfluidics and tissue engineering is an alternative model for disease study and preclinical drug discovery.