Honors & Awards
Career Development Award (K grant), NIH (NCI) (2017-2021)
Mogam Scientific Scholarship, Mogam Scientific Foundation (2006)
Ph.D., Stanford University (2010)
B.S., POSTECH (2001)
Current Research and Scholarly Interests
One of the key characteristics of life is the dynamic cross-scale interactions across different levels of biological organization, such as molecules, genes, cells, tissues, organs and an organism, in their own multi-scaled environmental contexts. The dynamic property of these interactions results in variation in physiological traits across individuals, shaping individuality of an organism. The overall research direction of my laboratory is to establish in vitro experimental platforms in which we can investigate this cross-scale interaction efficiently to develop personalized therapeutic strategies. Because many aspects of cross-scale interactions are mediated by blood circulation and crosstalk between the vasculature and perivascular tissues, our current efforts are focused on engineering the functional vasculatures in pathophysiological conditions of various human tissues. We have successfully developed in vitro experimental models equipped with the capacity of real-time monitoring of individual cell behaviors, which enables effective identification of the vascular routes that induce desirable behaviors of endogenous or exogenously grafted cells. Our in vitro model allows precise and independent control of the experimental parameters in highly time- and cost- efficient ways and facilitates the development of therapeutic and preventive treatment strategies in consideration of the phenotype variations across the patient population.
A neurovascular-unit-on-a-chip for the evaluation of the restorative potential of stem cell therapies for ischaemic stroke.
Nature biomedical engineering
The therapeutic efficacy of stem cells transplanted into an ischaemic brain depends primarily on the responses of the neurovascular unit. Here, we report the development and applicability of a functional neurovascular unit on a microfluidic chip as a microphysiological model of ischaemic stroke that recapitulates the function of the blood-brain barrier as well as interactions between therapeutic stem cells and host cells (human brain microvascular endothelial cells, pericytes, astrocytes, microglia and neurons). We used the model to track the infiltration of a number of candidate stem cells and to characterize the expression levels of genes associated with post-stroke pathologies. We observed that each type of stem cell showed unique neurorestorative effects, primarily by supporting endogenous recovery rather than through direct cell replacement, and that the recovery of synaptic activities is correlated with the recovery of the structural and functional integrity of the neurovascular unit rather than with the regeneration of neurons.
View details for DOI 10.1038/s41551-021-00744-7
View details for PubMedID 34385693
Engineering Three-Dimensional Vascularized Cardiac Tissues.
Tissue engineering. Part B, Reviews
Heart disease is one of the largest burdens to human health worldwide and has very limited therapeutic options. Engineered three-dimensional (3D) vascularized cardiac tissues have shown promise in rescuing cardiac function in diseased hearts and may serve as a whole organ replacement in the future. One of the major obstacles in reconstructing these thick myocardial tissues to a clinically applicable scale is the integration of functional vascular networks capable of providing oxygen and nutrients throughout whole engineered constructs. Without perfusion of oxygen and nutrient flow throughout the entire engineered tissue, not only is tissue viability compromised, but overall tissue functionality is lost. There are many supporting technologies and approaches that have been developed to create vascular networks such as 3D bioprinting, co-culturing hydrogels, and incorporation of soluble angiogenic factors. In this state-of-the-art review we discuss some of the most current engineered vascular cardiac tissues reported in the literature and future directions in the field.
View details for DOI 10.1089/ten.TEB.2020.0343
View details for PubMedID 33559514
A versatile system to record cell-cell interactions.
Cell-cell interactions influence all aspects of development, homeostasis, and disease. In cancer, interactions between cancer cells and stromal cells play a major role in nearly every step of carcinogenesis. Thus, the ability to record cell-cell interactions would facilitate mechanistic delineation of the role of cancer microenvironment. Here, we describe GFP-based Touching Nexus (G-baToN) which relies upon nanobody-directed fluorescent protein transfer to enable sensitive and specific labeling of cells after cell-cell interactions. G-baToN is a generalizable system that enables physical contact-based labeling between various human and mouse cell types, including endothelial cell-pericyte, neuron-astrocyte, and diverse cancer-stromal cell pairs. A suite of orthogonal baToN tools enables reciprocal cell-cell labeling, interaction-dependent cargo transfer, and the identification of higher-order cell-cell interactions across a wide range of cell types. The ability to track physically interacting cells with these simple and sensitive systems will greatly accelerate our understanding of the outputs of cell-cell interactions in cancer as well as across many biological processes.
View details for DOI 10.7554/eLife.61080
View details for PubMedID 33025906
3D patterned stem cell differentiation using thermo-responsive methylcellulose hydrogel molds
2016; 6: 29408
Tissue-specific patterned stem cell differentiation serves as the basis for the development, remodeling, and regeneration of the multicellular structure of the native tissues. We herein proposed a cytocompatible 3D casting process to recapitulate this patterned stem cell differentiation for reconstructing multicellular tissues in vitro. We first reconstituted the 2D culture conditions for stem cell fate control within 3D hydrogel by incorporating the sets of the diffusible signal molecules delivered through drug-releasing microparticles. Then, utilizing thermo-responsivity of methylcellulose (MC), we developed a cytocompatible casting process to mold these hydrogels into specific 3D configurations, generating the targeted spatial gradients of diffusible signal molecules. The liquid phase of the MC solution was viscous enough to adopt the shapes of 3D impression patterns, while the gelated MC served as a reliable mold for patterning the hydrogel prepolymers. When these patterned hydrogels were integrated together, the stem cells in each hydrogel distinctly differentiated toward individually defined fates, resulting in the formation of the multicellular tissue structure bearing the very structural integrity and characteristics as seen in vascularized bones and osteochondral tissues.
View details for DOI 10.1038/srep29408
View details for PubMedCentralID PMC4933913
Directed axonal outgrowth using a propagating gradient of IGF-1
2014; 26: 4936–4940
The temporospatial regulation of axon outgrowth is useful for guiding de novo connectivity or re-connectivity of neurons in neurological injury or disease. Here we report the successful construction of a biocompatible guidance device, in which a linear propagation of IGF-1 gradient sequentially directs axon outgrowth. We observe the extensive in vitro axonal extension over 5 mm with a desired growth rate of ∼1 mm/day.
View details for DOI 10.1002/adma.201305995
The Design of a Heterocellular 3D Architecture and its Application to Monitoring the Behavior of Cancer Cells in Response to the Spatial Distribution of Endothelial Cells
2012; 24 (39): 5339-5344
The spatial cell distribution is one of the critical features for governing cellular interactions and their consequent behaviors. Here we suggest a novel method of building a hierarchical cellular structure by stacking cell-attached microplate structures with specific configurations within hydrogel layers. This method is applied to the reconstruction of the 3D architecture of a liver lobule and the development of an experimental model of the various phases of cancer angiogenesis.
View details for DOI 10.1002/adma.201200687
View details for Web of Science ID 000309405200006
View details for PubMedID 22927197
Hydrophobic nanoparticles improve permeability of cell-encapsulating poly(ethylene glycol) hydrogels while maintaining patternability
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2010; 107 (48): 20709-20714
Cell encapsulating poly(ethylene glycol) hydrogels represent a promising approach for constructing 3D cultures designed to more closely approximate in vivo tissue environment. Improved strategies are needed, however, to optimally balance hydrogel permeability to support metabolic activities of encapsulated cells, while maintaining patternability to restore key aspects of tissue architecture. Herein, we have developed one such strategy incorporating hydrophobic nanoparticles to partially induce looser cross-linking density at the particle-hydrogel interface. Strikingly, our network design significantly increased hydrogel permeability, while only minimally affecting the matrix mechanical strength or prepolymer viscosity. This structural advantage improved viability and functions of encapsulated cells and permitted micron-scale structures to control over spatial distribution of incorporated cells. We expect that this design strategy holds promise for the development of more advanced artificial tissues that can promote high levels of cell metabolic activity and recapitulate key architectural features.
View details for DOI 10.1073/pnas.1005211107
View details for PubMedID 21071674
The reliable targeting of specific drug release profiles by integrating arrays of different albumin-encapsulated microsphere types
2009; 30 (34): 6648-6654
Biodegradable polymer microspheres have been successfully utilized as a medium for controlled protein or peptide-based drug release. Because the release kinetics has been typically controlled by modulating physical or chemical properties of the medium, these parameters must be optimized to obtain a specific release profile. However, due to the complexity of the release mechanism and the complicated interplay between various design parameters of the release medium, detailed prediction of the resulting release profile is a challenge. Herein we suggest a simple method to target specific release profiles more efficiently by integrating release profiles for an array of different microsphere types. This scheme is based on our observation that the resulting release profile from a mixture of different samples can be predicted as the linear summation of the individually measured release profiles of each sample. Hence, by employing a linear equation at each time point and formulating them as a matrix equation, we could determine how much of each microsphere type to include in a mixture in order to have a specific release profile. In accordance with this method, several targeted release profiles were successfully obtained. We expect that the proposed method will allow us to overcome limitations in controlling complicated release mechanisms so that drug delivery systems can be reliably designed to satisfy clinical demands.
View details for DOI 10.1016/j.biomaterials.2009.08.035
View details for PubMedID 19775742
Viral infection of human progenitor and liver-derived cells encapsulated in three-dimensional PEG-based hydrogel
2009; 4 (1)
We have studied the encapsulation of human progenitor cells into 3D PEG hydrogels. Replication-incompetent lentivirus promoter reporter vectors were found to efficiently detect the in vivo expression of human hepatic genes in hydrogel-encapsulated liver progenitor cells. Similarly, hydrogel-encapsulated cells could be efficiently infected with hepatitis C virus, and progeny infectious virus could be recovered from the media supernatants of the hydrogels. Provocatively, the diameters of these virus particles range from approximately 50 to 100 nm, while the calculated mesh size of the 8 k hydrogel is 44.6 +/- 1.7 A. To reconcile how viral particles can penetrate the hydrogels to infect the encapsulated cells, we propose that microfractures/defects of the hydrogel result in a functional pore size of up to 20 fold greater than predicted by theoretical mesh calculations. These results suggest a new model of hydrogel structure, and have exciting implications for tissue engineering and hepatitis virus studies.
View details for DOI 10.1088/1748-6041/4/1/011001
View details for PubMedID 18981544