Bio


Soah is a biomaterials scientist and bio engineer who specializes in developing artificial cell niche using hydrogels for various tissue engineering/drug delivery applications.

During 5 years of Ph.D. training in Stem Cell and Biomaterials Laboratory under Dr. Fan Yang's guidance, Soah has focused on developing novel hydrogel-based cell niche platforms and examining effect of biophysical properties of the cell niche using various natural polymers (Matrigel, collagen, alginate, etc.) and synthetic polymers (poly(ethylene glycol), poly(acryl amide) etc.).

After completion of her Ph.D. training, she has joined Sean Wu's lab in CVI to extend her expertise in biomaterials to develop a bioink for bioprinting 3D cardiac tissues.

Honors & Awards


  • Centennial TA Awards 2015, Stanford University (June. 2015)
  • Bio-X Fellowship, Stanford Bio-X, Stanford University (Sep. 2012 - Aug. 2015)
  • Department Fellowship, Department of Materials Science and Engineering, Stanford University (Sep. 2011 - Aug. 2012)
  • National Scholarship for Science and Engineering, Korea Student Aid Foundation (Mar. 2007 - Feb. 2011)

Professional Education


  • Doctor of Philosophy, Stanford University, MATSC-PHD (2016)
  • Master of Science, Stanford University, MATSC-MS (2015)
  • Bachelor of Science, Seoul National University, Materials Science& Engineering (2011)

Lab Affiliations


All Publications


  • Levitating Cells to Sort the Fit and the Fat. Advanced biosystems Puluca, N., Durmus, N. G., Lee, S., Belbachir, N., Galdos, F. X., Ogut, M. G., Gupta, R., Hirano, K. I., Krane, M., Lange, R., Wu, J. C., Wu, S. M., Demirci, U. 2020: e1900300

    Abstract

    Density is a core material property and varies between different cell types, mainly based on differences in their lipid content. Sorting based on density enables various biomedical applications such as multi-omics in precision medicine and regenerative repair in medicine. However, a significant challenge is sorting cells of the same type based on density differences. Here, a new method for real-time monitoring and sorting of single cells based on their inherent levitation profiles driven by their lipid content is reported. As a model system, human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) from a patient with neutral lipid storage disease (NLSD) due to loss of function of adipose triglyceride lipase (ATGL) resulting in abnormal lipid storage in cardiac muscle are used. This levitation-based strategy detects subpopulations within ATGL-deficient hiPSC-CMs with heterogenous lipid content, equilibrating at different levitation heights due to small density differences. In addition, sorting of these differentially levitating subpopulations are monitored in real time. Using this approach, sorted healthy and diseased hiPSC-CMs maintain viability and function. Pixel-tracking technologies show differences in contraction between NLSD and healthy hiPSC-CMs. Overall, this is a unique approach to separate diseased cell populations based on their intracellular lipid content that cannot be achieved using traditional flow cytometry techniques.

    View details for DOI 10.1002/adbi.201900300

    View details for PubMedID 32352239

  • Simple Lithography-Free Single Cell Micropatterning using Laser-Cut Stencils. Journal of visualized experiments : JoVE Lee, S., Yang, H., Chen, C., Venkatraman, S., Darsha, A., Wu, S. M., Wu, J. C., Seeger, T. 2020

    Abstract

    Micropatterning techniques have been widely used in cell biology to study effects of controlling cell shape and size on cell fate determination at single cell resolution. Current state-of-the-art single cell micropatterning techniques involve soft lithography and micro-contact printing, which is a powerful technology, but requires trained engineering skills and certain facility support in microfabrication. These limitations require a more accessible technique. Here, we describe a simple alternative lithography-free method: stencil-based single cell patterning. We provide step-by-step procedures including stencil design, polyacrylamide hydrogel fabrication, stencil-based protein incorporation, and cell plating and culture. This simple method can be used to pattern an array of as many as 2,000 cells. We demonstrate the patterning of cardiomyocytes derived from single human induced pluripotent stem cells (hiPSC) with distinct cell shapes, from a 1:1 square to a 7:1 adult cardiomyocyte-like rectangle. This stencil-based single cell patterning is lithography-free, technically robust, convenient, inexpensive, and most importantly accessible to those with a limited bioengineering background.

    View details for DOI 10.3791/60888

    View details for PubMedID 32310234

  • Hydrogels with enhanced protein conjugation efficiency reveal stiffness-induced YAP localization in stem cells depends on biochemical cues BIOMATERIALS Lee, S., Stanton, A. E., Tong, X., Yang, F. 2019; 202: 26–34
  • Biochemical Ligand Density Regulates Yes-Associated Protein Translocation in Stem Cells through Cytoskeletal Tension and Integrins ACS APPLIED MATERIALS & INTERFACES Stanton, A. E., Tong, X., Lee, S., Yang, F. 2019; 11 (9): 8849–57

    Abstract

    Different tissue types are characterized by varying stiffness and biochemical ligands. Increasing substrate stiffness has been shown to trigger Yes-associated protein (YAP) translocation from the cytoplasm to the nucleus, yet the role of ligand density in modulating mechanotransduction and stem cell fate remains largely unexplored. Using polyacrylamide hydrogels coated with fibronectin as a model platform, we showed that stiffness-induced YAP translocation occurs only at intermediate ligand densities. At low or high ligand densities, YAP localization is dominated by ligand density independent of substrate stiffness. We further showed that ligand density-induced YAP translocation requires cytoskeleton tension and αVβ3-integrin binding. Finally, we demonstrate that increasing ligand density alone can enhance osteogenic differentiation regardless of matrix stiffness. Together, the findings from the present study establish ligand density as an important parameter for modulating stem cell mechanotransduction and differentiation, which is mediated by integrin clustering, focal adhesion, and cytoskeletal tension.

    View details for DOI 10.1021/acsami.8b21270

    View details for Web of Science ID 000460996900018

    View details for PubMedID 30789697

  • Hydrogels with enhanced protein conjugation efficiency reveal stiffness-induced YAP localization in stem cells depends on biochemical cues. Biomaterials Lee, S., Stanton, A. E., Tong, X., Yang, F. 2019; 202: 26–34

    Abstract

    Polyacrylamide hydrogels have been widely used in stem cell mechanotransduction studies. Conventional conjugation methods of biochemical cues to polyacrylamide hydrogels suffer from low conjugation efficiency, which leads to poor attachment of human pluripotent stem cells (hPSCs) on soft substrates. In addition, while it is well-established that stiffness-dependent regulation of stem cell fate requires cytoskeletal tension, and is mediated through nuclear translocation of transcription regulator, Yes-associated protein (YAP), the role of biochemical cues in stiffness-dependent YAP regulation remains largely unknown. Here we report a method that enhances the conjugation efficiency of biochemical cues on polyacrylamide hydrogels compared to conventional methods. This modified method enables robust hPSC attachment, proliferation and maintenance of pluripotency across varying substrate stiffness (3 kPa-38 kPa). Using this hydrogel platform, we demonstrate that varying the types of biochemical cues (Matrigel, laminin, GAG-peptide) or density of Matrigel can alter stiffness-dependent YAP localization in hPSCs. In particular, we show that stiffness-dependent YAP localization is overridden at low or high density of Matrigel. Furthermore, human mesenchymal stem cells display stiffness-dependent YAP localization only at intermediate fibronectin density. The hydrogel platform with enhanced conjugation efficiency of biochemical cues provides a powerful tool for uncovering the role of biochemical cues in regulating mechanotransduction of various stem cell types.

    View details for PubMedID 30826537

  • Bioprinting Approaches to Engineering Vascularized 3D Cardiac Tissues. Current cardiology reports Puluca, N., Lee, S., Doppler, S., Münsterer, A., Dreßen, M., Krane, M., Wu, S. M. 2019; 21 (9): 90

    Abstract

    3D bioprinting technologies hold significant promise for the generation of engineered cardiac tissue and translational applications in medicine. To generate a clinically relevant sized tissue, the provisioning of a perfusable vascular network that provides nutrients to cells in the tissue is a major challenge. This review summarizes the recent vascularization strategies for engineering 3D cardiac tissues.Considerable steps towards the generation of macroscopic sizes for engineered cardiac tissue with efficient vascular networks have been made within the past few years. Achieving a compact tissue with enough cardiomyocytes to provide functionality remains a challenging task. Achieving perfusion in engineered constructs with media that contain oxygen and nutrients at a clinically relevant tissue sizes remains the next frontier in tissue engineering. The provisioning of a functional vasculature is necessary for maintaining a high cell viability and functionality in engineered cardiac tissues. Several recent studies have shown the ability to generate tissues up to a centimeter scale with a perfusable vascular network. Future challenges include improving cell density and tissue size. This requires the close collaboration of a multidisciplinary teams of investigators to overcome complex challenges in order to achieve success.

    View details for DOI 10.1007/s11886-019-1179-8

    View details for PubMedID 31352612

  • A Premature Termination Codon Mutation in MYBPC3 Causes Hypertrophic Cardiomyopathy via Chronic Activation of Nonsense-Mediated Decay. Circulation Seeger, T., Shrestha, R., Lam, C. K., Chen, C., McKeithan, W. L., Lau, E., Wnorowski, A., McMullen, G., Greenhaw, M., Lee, J., Oikonomopoulos, A., Lee, S., Yang, H., Mercola, M., Wheeler, M., Ashley, E. A., Yang, F., Karakikes, I., Wu, J. C. 2018

    Abstract

    BACKGROUND: Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in myosin binding protein C3 ( MYBPC3) resulting in a premature termination codon (PTC). The underlying mechanisms of how PTC mutations in MYBPC3 lead to the onset and progression of HCM are poorly understood. This study's aim was to investigate the molecular mechanisms underlying the pathogenesis of HCM associated with MYBPC3 PTC mutations by utilizing human isogenic induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs).METHODS: Isogenic iPSC lines were generated from patients harboring MYBPC3 PTC mutations (p.R943x; p.R1073P_Fsx4) using genome editing and then differentiated into cardiomyocytes. Comprehensive phenotypical and transcriptome analyses were performed.RESULTS: We observed aberrant calcium handling properties with prolonged decay kinetics and elevated diastolic calcium levels in HCM iPSC-CMs compared to isogenic controls without structural abnormalities or contractile dysfunction. The mRNA expression levels of MYBPC3 were significantly reduced in mutant iPSC-CMs, but the protein levels were comparable among isogenic iPSC-CMs, suggesting that haploinsufficiency of MYBPC3 does not contribute to the pathogenesis of HCM in vitro. Furthermore, truncated MYBPC3 peptides were not detected. At the molecular level, the nonsense-mediated decay (NMD) pathway was activated, and a set of genes involved in major cardiac signaling pathways was dysregulated in HCM iPSC-CMs, indicating an HCM gene signature in vitro. Specific inhibition of the NMD pathway in mutant iPSC-CMs resulted in reversal of the molecular phenotype and normalization of calcium handling abnormalities.CONCLUSIONS: iPSC-CMs carrying MYBPC3 PTC mutations displayed aberrant calcium signaling and molecular dysregulations in the absence of significant haploinsufficiency of MYBPC3 protein. Here we provided the first evidence of the direct connection between the chronically activated NMD pathway and HCM disease development.

    View details for PubMedID 30586709

  • Bioacoustic-enabled patterning of human iPSC-derived cardiomyocytes into 3D cardiac tissue BIOMATERIALS Serpooshan, V., Chen, P., Wu, H., Lee, S., Sharma, A., Hu, D. A., Venkatraman, S., Ganesan, A. V., Usta, O. B., Yarmush, M., Yang, F., Wu, J. C., Demirci, U., Wu, S. M. 2017; 131: 47-57

    Abstract

    The creation of physiologically-relevant human cardiac tissue with defined cell structure and function is essential for a wide variety of therapeutic, diagnostic, and drug screening applications. Here we report a new scalable method using Faraday waves to enable rapid aggregation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) into predefined 3D constructs. At packing densities that approximate native myocardium (10(8)-10(9) cells/ml), these hiPSC-CM-derived 3D tissues demonstrate significantly improved cell viability, metabolic activity, and intercellular connection when compared to constructs with random cell distribution. Moreover, the patterned hiPSC-CMs within the constructs exhibit significantly greater levels of contractile stress, beat frequency, and contraction-relaxation rates, suggesting their improved maturation. Our results demonstrate a novel application of Faraday waves to create stem cell-derived 3D cardiac tissue that resembles the cellular architecture of a native heart tissue for diverse basic research and clinical applications.

    View details for DOI 10.1016/j.biomaterials.2017.03.037

    View details for PubMedID 28376365

  • Contractile force generation by 3D hiPSC-derived cardiac tissues is enhanced by rapid establishment of cellular interconnection in matrix with muscle-mimicking stiffness BIOMATERIALS Lee, S., Serpooshan, V., Tong, X., Venkatraman, S., Lee, M., Lee, J., Chirikian, O., Wu, J. C., Wu, S. M., Yang, F. 2017; 131: 111-120

    Abstract

    Engineering 3D human cardiac tissues is of great importance for therapeutic and pharmaceutical applications. As cardiac tissue substitutes, extracellular matrix-derived hydrogels have been widely explored. However, they exhibit premature degradation and their stiffness is often orders of magnitude lower than that of native cardiac tissue. There are no reports on establishing interconnected cardiomyocytes in 3D hydrogels at physiologically-relevant cell density and matrix stiffness. Here we bioengineer human cardiac microtissues by encapsulating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in chemically-crosslinked gelatin hydrogels (1.25 × 10(8)/mL) with tunable stiffness and degradation. In comparison to the cells in high stiffness (16 kPa)/slow degrading hydrogels, hiPSC-CMs in low stiffness (2 kPa)/fast degrading and intermediate stiffness (9 kPa)/intermediate degrading hydrogels exhibit increased intercellular network formation, α-actinin and connexin-43 expression, and contraction velocity. Only the 9 kPa microtissues exhibit organized sarcomeric structure and significantly increased contractile stress. This demonstrates that muscle-mimicking stiffness together with robust cellular interconnection contributes to enhancement in sarcomeric organization and contractile function of the engineered cardiac tissue. This study highlights the importance of intercellular connectivity, physiologically-relevant cell density, and matrix stiffness to best support 3D cardiac tissue engineering.

    View details for DOI 10.1016/j.biomaterials.2017.03.039

    View details for PubMedID 28384492

  • Winner of the Young Investigator Award of the Society for Biomaterials (USA) for 2016, 10th World Biomaterials Congress, May 17-22, 2016, Montreal QC, Canada: Aligned microribbon-like hydrogels for guiding three-dimensional smooth muscle tissue regeneration JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Lee, S., Tong, X., Han, L., Behn, A., Yang, F. 2016; 104 (5): 1064-1071

    Abstract

    Smooth muscle tissue is characterized by aligned structures, which is critical for its contractile functions. Smooth muscle injury is common and can be caused by various diseases and degenerative processes, and there remains a strong need to develop effective therapies for smooth muscle tissue regeneration with restored structures. To guide cell alignment, previously cells were cultured on 2D nano/microgrooved substrates, but such method is limited to fabricating 2D aligned cell sheets only. Alternatively, aligned electrospun nanofiber has been employed as 3D scaffold for cell alignment, but cells can only be seeded post fabrication, and nanoporosity of electrospun fiber meshes often leads to poor cell distribution. To overcome these limitations, we report aligned gelatin-based microribbons (µRBs) as macroporous hydrogels for guiding smooth muscle alignment in 3D. We developed aligned µRB-like hydrogels using wet spinning, which allows easy fabrication of tissue-scale (cm) macroporous matrices with alignment cues and supports direct cell encapsulation. The macroporosity within µRB-based hydrogels facilitated cell proliferation, new matrix deposition, and nutrient diffusion. In aligned µRB scaffold, smooth muscle cells showed high viability, rapid adhesion, and alignment following µRB direction. Aligned µRB scaffolds supported retention of smooth muscle contractile phenotype, and accelerated uniaxial deposition of new matrix (collagen I/IV) along the µRB. In contrast, cells encapsulated in conventional gelatin hydrogels remained round with matrix deposition limited to pericellular regions only. We envision such aligned µRB scaffold can be broadly applicable in growing other anisotropic tissues including tendon, nerves and blood vessel. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1064-1071, 2016.

    View details for DOI 10.1002/jbm.a.35662

    View details for PubMedID 26799256

  • Effects of the poly(ethylene glycol) hydrogel crosslinking mechanism on protein release. Biomaterials science Lee, S., Tong, X., Yang, F. 2016; 4 (3): 405-411

    Abstract

    Poly(ethylene glycol) (PEG) hydrogels are widely used to deliver therapeutic biomolecules, due to high hydrophilicity, tunable physicochemical properties, and anti-fouling properties. Although different hydrogel crosslinking mechanisms are known to result in distinct network structures, it is still unknown how these various mechanisms influence biomolecule release. Here we compared the effects of chain-growth and step-growth polymerization for hydrogel crosslinking on the efficiency of protein release and diffusivity. For chain-growth-polymerized PEG hydrogels, while decreasing PEG concentration increased both the protein release efficiency and diffusivity, it was unexpected to find out that increasing PEG molecular weight did not significantly change either parameter. In contrast, for step-growth-polymerized PEG hydrogels, both decreasing PEG concentration and increasing PEG molecular weight resulted in an increase in the protein release efficiency and diffusivity. For step-growth-polymerized hydrogels, the protein release efficiency and diffusivity were further decreased by increasing crosslink functionality (4-arm to 8-arm) of the chosen monomer. Altogether, our results demonstrate that the crosslinking mechanism has a differential effect on controlling protein release, and this study provides valuable information for the rational design of hydrogels for sophisticated drug delivery.

    View details for DOI 10.1039/c5bm00256g

    View details for PubMedID 26539660

  • Long-Term Controlled Protein Release from Poly(Ethylene Glycol) Hydrogels by Modulating Mesh Size and Degradation MACROMOLECULAR BIOSCIENCE Tong, X., Lee, S., Bararpour, L., Yang, F. 2015; 15 (12): 1679-1686

    Abstract

    Poly(ethylene glycol) (PEG)-based hydrogels are popular biomaterials for protein delivery to guide desirable cellular fates and tissue repair. However, long-term protein release from PEG-based hydrogels remains challenging. Here, we report a PEG-based hydrogel platform for long term protein release, which allows efficient loading of proteins via physical entrapment. Tuning hydrogel degradation led to increase in hydrogel mesh size and gradual release of protein over 60 days of with retained bioactivity. Importantly, this platform does not require the chemical modification of loaded proteins, and may serve as a versatile tool for long-term delivery of a wide range of proteins for drug-delivery and tissue-engineering applications.

    View details for DOI 10.1002/mabi.201500245

    View details for Web of Science ID 000368456500007

    View details for PubMedCentralID PMC5127624

  • Long-Term Controlled Protein Release from Poly(Ethylene Glycol) Hydrogels by Modulating Mesh Size and Degradation. Macromolecular bioscience Tong, X., Lee, S., Bararpour, L., Yang, F. 2015; 15 (12): 1679–86

    Abstract

    Poly(ethylene glycol) (PEG)-based hydrogels are popular biomaterials for protein delivery to guide desirable cellular fates and tissue repair. However, long-term protein release from PEG-based hydrogels remains challenging. Here, we report a PEG-based hydrogel platform for long term protein release, which allows efficient loading of proteins via physical entrapment. Tuning hydrogel degradation led to increase in hydrogel mesh size and gradual release of protein over 60 days of with retained bioactivity. Importantly, this platform does not require the chemical modification of loaded proteins, and may serve as a versatile tool for long-term delivery of a wide range of proteins for drug-delivery and tissue-engineering applications.

    View details for PubMedID 26259711

  • The effects of varying poly(ethylene glycol) hydrogel crosslinking density and the crosslinking mechanism on protein accumulation in three-dimensional hydrogels ACTA BIOMATERIALIA Lee, S., Tong, X., Yang, F. 2014; 10 (10): 4167-4174

    Abstract

    Matrix stiffness has been shown to play an important role in modulating various cell fate processes such as differentiation and cell cycle. Given that the stiffness can be easily tuned by varying the crosslinking density, poly(ethylene glycol) (PEG) hydrogels have been widely used as an artificial cell niche. However, little is known about how changes in the hydrogel crosslinking density may affect the accumulation of exogenous growth factors within 3-D hydrogel scaffolds formed by different crosslinking mechanisms. To address such shortcomings, we measured protein diffusivity and accumulation within PEG hydrogels with varying PEG molecular weight, concentration and crosslinking mechanism. We found that protein accumulation increased substantially above a critical mesh size, which was distinct from the protein diffusivity trend, highlighting the importance of using protein accumulation as a parameter to better predict the cell fates in addition to protein diffusivity, a parameter commonly reported by researchers studying protein diffusion in hydrogels. Furthermore, we found that chain-growth-polymerized gels allowed more protein accumulation than step-growth-polymerized gels, which may be the result of network heterogeneity. The strategy used here can help quantify the effects of varying the hydrogel crosslinking density and crosslinking mechanism on protein diffusion in different types of hydrogel. Such tools could be broadly useful for interpreting cellular responses in hydrogels of varying stiffness for various tissue engineering applications.

    View details for DOI 10.1016/j.actbio.2014.05.023

    View details for Web of Science ID 000342523800011

  • The effects of varying poly(ethylene glycol) hydrogel crosslinking density and the crosslinking mechanism on protein accumulation in three-dimensional hydrogels. Acta biomaterialia Lee, S., Tong, X., Yang, F. 2014; 10 (10): 4167-4174

    Abstract

    Matrix stiffness has been shown to play an important role in modulating various cell fate processes such as differentiation and cell cycle. Given that the stiffness can be easily tuned by varying the crosslinking density, poly(ethylene glycol) (PEG) hydrogels have been widely used as an artificial cell niche. However, little is known about how changes in the hydrogel crosslinking density may affect the accumulation of exogenous growth factors within 3-D hydrogel scaffolds formed by different crosslinking mechanisms. To address such shortcomings, we measured protein diffusivity and accumulation within PEG hydrogels with varying PEG molecular weight, concentration and crosslinking mechanism. We found that protein accumulation increased substantially above a critical mesh size, which was distinct from the protein diffusivity trend, highlighting the importance of using protein accumulation as a parameter to better predict the cell fates in addition to protein diffusivity, a parameter commonly reported by researchers studying protein diffusion in hydrogels. Furthermore, we found that chain-growth-polymerized gels allowed more protein accumulation than step-growth-polymerized gels, which may be the result of network heterogeneity. The strategy used here can help quantify the effects of varying the hydrogel crosslinking density and crosslinking mechanism on protein diffusion in different types of hydrogel. Such tools could be broadly useful for interpreting cellular responses in hydrogels of varying stiffness for various tissue engineering applications.

    View details for DOI 10.1016/j.actbio.2014.05.023

    View details for PubMedID 24887284