Office: Foege N410G
South Lake Union campus:
Office: 850 Republican St. Rm 418
Mechanobiology and mechanotransduction
Micro- and nanofabricated biomaterials
Quantitative live cell imaging analysis
BioMEMS and nanobiotechnology
Microfluidics and soft lithography
Micro and nanoengineering of the cell microenvironment
Our current research focuses on engineering combinatorial cellular microenvironment through use of variable nano-patterns, and soluble and matrix-bound cell guidance cues in a single experiment, which better mimics the in vivo microenvironment under physiological conditions. Using these tools, we strive to systematically characterize live cells to wide spectra of dynamically changing combination of mechanical and chemical stimuli (e.g. ECM proteins, topographic, growth factors and signal transduction pathway inhibitors). The proposed measurements are highly resolved in time and space, using a variety of live cell probes and highly defined extracellular conditions. Using cost-effective, scalable nanofabrication techniques, we are developing biomimetic nanotopographically-defined cell culture models and biomaterial tissue scaffolds. We aim to use these tools to gain new mechanistic insights into cell signaling and function, to design new therapies or diagnostic tests for cancer progression and cardiovascular diseases, and to establish organizing principles for development of precisely defined scaffolds for advanced tissue engineering applications.
Mechanical control of cell function and tissue morphogenesis
Mechanotransduction – from how cells sense mechanical forces in different tissues to how these mechanical forces are transduced into biochemical signals – is an essential biological process in development, normal physiology and disease. In this exciting area, we are particularly interested in investigating the role of mechano-biological processes associated with cell-cell and cell-matrix adhesions (e.g. topography and rigidity of the extracellular matrix) in the regulation of collective and directed cell migration and tissue morphogenesis. Using a combination of various techniques, from molecular biology to nanotechnology and live cell imaging, for example, we have been accumulating interesting data suggesting that one of the most important factors distinguishing metastatic from non-metastatic cells could be their ability to collectively invade and migrate towards blood vessels by physically interacting with the surrounding extracellular matrices. By experimenting with the nanotopographically-defined cell adhesion substratum (i.e. quasi 3D cell culture system) and 3D natural/synthetic extracellular matrices, we are investigating the biophysical and signaling mechanisms of collective cell migration driven by the hypothesis that the physical interaction of migrating cells with the surrounding ECM has a crucial role in the collective guidance of cell migration in the context of cancer invasion and wound healing. To test this hypothesis, we recently developed a micro/nanofabricated collective migration assay as an enabling tool for analysis and control of cancer cell invasion and epithelial/endothelial wound healing in a high-throughput, controlled manner. Using these tools, we also explore the potential role of mechanical guidance in the regulation of collective cell migration and tissue morphogenesis under the presence/absence of growth factor-induced signals, and test their biomedical implication by screening cytoskeletal and signal transduction pathways.
Microenvironmental stem cell niche engineering and cardiovascular tissue engineering
With advances in nanofabrication and biomaterials, scaffolding materials can be designed to integrate biomimetic structural and mechanical cues present in the in vivo ECM environment. Based on ultrastructural analyses of the native heart tissue, we are developing a bio-inspired model cardiac tissue to better understand cardiac tissue structure-function relationships, and to seek applications in stem cell-based therapies for myocardial regeneration. The ultimate goal of this project is to develop nanopatterned functional cardiac patches for treating the damaged heart tissue (e.g. myocardial infarction). The working hypothesis is that cultivation of cardiac cells and/or stem cells on novel biomaterials scaffolds integrated with nanotopographic cues promotes biomimetic anisotropic assembly of uniformly contractile engineered muscle, while simultaneously enabling control over local cell alignment. We further envision that integrating the transplantable stem cells with the proposed nano-grafting techniques have therapeutic potential in repairing cardiac tissue damage and may prevent the onset of heart failure. In order to test these hypotheses, our research focuses on elucidating the relationships between scaffold-mediated nanostructural cues and tissue engineered cardiac graft contractility and function. In addition, the therapeutic potential of a nanopatterned cardiac stem cell graft will be studied in vitro and in vivo (implantation onto the left ventricle in an adult rat model of myocardial infarction). Tissue structure and function will be characterized at various hierarchical scales (molecular, structural, functional) and the obtained experimental data will be used to tailor the conditions and duration of cultivation, leading to engineering implantable grafts.
Research Scientist, Korea Institute of Science and Technology, 2000-2005
Visiting Scientist, Swiss Federal Institute of Technology at Zurich, Switzerland, 2003-2004
MS (mechanical engineering), Seoul National University, 2000
BS (mechanical engineering), Pohang University of Science and Technology (POSTECH), 1998
2013: American Heart Association Scientist Development Grant Award
2011: Perkins Coie Award for Discovery
2010: Harold M. Weintraub Award in the Biological Sciences
2009: Samsung HumanTech Thesis Award – Silver Prize.
2008: The First Baltimore Life Scientists Association (BLSA) Outstanding Scientist Award
2008-2010: American Heart Association Predoctoral Fellowship
2007: The First Surface Engineering Best Paper Award, the Society of Tribologists and Lubrication Engineers.
2005: Distinguished Achievement Award of KIST (“KIST Award of the Month”)
2004: Prize for Excellent Researcher of the year, Future Technology Research Division, KIST
1999: Best Student Paper Award, the Korean Society of Mechanical Engineers
1999: Best Student Poster Paper Award, the Korean Society of Precision Engineers
1996: Hogil-Kim Memorial Fellow Exchange Student, University of Birmingham, UK
BIOEN 498/599: Mechanobiology
B. Lee, A. Jiao, S.J. Yu, J.B. You, D.H. Kim#, and S.K. Im#, “Initiated chemical vapor deposition of thermoresponsive poly(N-vinylcaprolactam) thin films for cell sheet engineering,” Acta Biomaterialia, vol. 9, pp. 7691-7698, 2013.
M. E. Hubbi, Kshitiz, D.M. Gilkes, S. Rey, C. C. Wong, W. Luo, D.H. Kim, C. V. Dang, A. Levchenko, and G. Semenza, “A non-transcriptional role for HIF-1α as a direct inhibitor of DNA replication,” Science Signaling, vol. 6, pp. ra10, 2013. (Featured as a Front Cover)
H. N. Kim, A. Jiao1, N. Hwang, M.S. Kim, D.H. Kang, D.H. Kim, and K. Suh, “Nanotopography-guided tissue engineering and regenerative medicine,” Advanced Drug Delivery Reviews, vol. 65, pp. 536-558, 2013. (Featured as a Front Cover)
D.H. Kim, Kshitiz, R. R. Smith, P. Kim, E. H. Ahn, H.N. Kim, E Marban, K.Y. Suh, and A. Levchenko, “Nanopatterned cardiac cell patches promote stem cell niche formation and myocardial regeneration” Integrative Biology, Vol. 4, Issue 9,pp. 1019-1033, 2012 (Featured as a Cover Article)
Kshitiz, J.S. Park, P. Kim, W. Helen, A.J. Engler, A. Levchenko, and D.H. Kim#, “Control of stem cell fate and function by engineering physical microenvironments” Integrative Biology, Vol. 9, pp. 1008-1018, 2012.
D.H. Kim, P. Provenzano, C.L. Smith, and A. Levchenko, “Matrix nanotopography as regulator of cell function,” Journal of Cell Biology vol. 197 no. 3 pp. 351-360, 2012.
Kshitiz, M.E. Hubbi, E.H. Ahn, J. Downey, D.H. Kim, S. Rey, J. Afzal, A. Kundo, G.L. Semenza, R. M. Abraham, and A. Levchenko, “Matrix rigidity controls endothelial differentiation and morphogenesis of cardiac precursors,” Science Signaling Vol. 5, Issue. 227, ra41, 2012. (Featured as a Cover Article)
J. Kim*, D.H. Kim*, K.T. Lim, H. Seonwoo, S.H. Park, Y.R. Kim, Y.H. Choung, P.H. Choung, and J.H. Chung, “Charged nanomatrices as efficient platforms for modulating cell adhesion and shape,” Tissue Engineering Part C, vol. 18, pp. 913-923, 2012. (Featured as a Front Cover)
Tomas Garzon-Muvdi, Paula Schiapparelli, Colette ap Rhys, Hugo Guerrero-Cazares, Christopher Smith, Deok-Ho Kim, Lyonell Kone, Harrison Farber, Danielle Y. Lee, Steven S. An, Andre Levchenko*, Alfredo Quiñones-Hinojosa*, “Regulation of Brain Tumor Dispersal by NKCC1 Through a Novel Role in Focal Adhesion Regulation,” PLoS Biology, Vol. 10, Issue. 5, e1001320, 2012
J.K. Kim, I. Hwang, D.M. Britain, T.D. Chung, Y. Sun, and D.H. Kim#, “Microfluidic approaches for gene delivery and gene therapy,” Lab on a Chip, vol. 11, pp. 3941-3948, 2011.
E. Hur*, I.H. Yang*, D.H. Kim*, J. Byun, W.-L. Xu, S. Jilafu, R. Cheong, A. Levchenko, N. Thakor, and F. Zhou, “Engineering neuronal growth cone to promote axon regeneration over inhibitory molecules,” Proceedings of the National Academy of Sciences USA, vol. 108, pp. 5057-5062, 2011. (*equal contribution).
K. Gupta, D.H. Kim, D. Beebe, and A. Levchenko, “Micro and nanoengineering for stem cell biology: the promise with a caution,” Trends in Biotechnology, vol. 29, pp. 399-408, 2011.
D.H. Kim, H.J. Lee, Y.K. Lee, J.M. Nam, and A. Levchenko, “Biomimetic nanopatterns as enabling tools for analysis and control of live cells,” Advanced Materials, vol. 22, pp.4551-4566, 2010.
K. Gupta*, D.H. Kim*, D. Ellison, C. Smith, A. Kundu, K.Y. Suh, J. Tuan, and A. Levchenko, “Lab-on-a-chip devices as an emerging platform for stem cell biology,” Lab on a Chip, vol. 10, pp.2019-2031, 2010. (*equal contribution)
M.H. You, M.K. Kwak, D.H. Kim, K. Kim, A. Levchenko, D.Y. Kim, and K.Y. Suh, “Synergistically enhanced osteogenic differentiation of human mesenchymal stem cells by culture on nanostructured surfaces with induction media,” Biomacromolecules, vol. 11, pp.1856-1862, 2010.
J. Park*, D.H. Kim*, G. Kim, Y.H. Kim, E. Choi, and A. Levchenko, “Simple haptotactic gradient generation within a triangular microfluidic channel,” Lab on a Chip, vol. 10, pp.2130-2138, 2010. (*equal contribution)
D.H. Kim, E. Lipke, P. Kim, R. Cheong, S. Edmonds, M. Delannoy, K.Y. Suh, L.Tung, and A. Levchenko, “Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs,” Proceedings of National Academy of Sciences USA, vol.107, pp. 565-570, 2010.
D.H. Kim, P. Wong, J.Y. Park, A. Levchenko, and Y. Sun, “Microengineered platforms for cell mechanobiology,” Annual Review of Biomedical Engineering, vol. 11, pp.203-233, 2009.
D.H. Kim, C. Seo, K. Han, K. Kwon, A. Levchenko and K.Y. Suh, “Guided cell migration on microtextured substrates with variable local density and anisotropy,” Advanced Functional Materials, vol.19, pp.1579-1586, 2009.
D.H. Kim, K. Han, K. Gupta, K. Kwon, K.Y. Suh, and A. Levchenko, “Mechanosensitivity of fibroblast cell shape and movement to anisotropic substratum topography gradients,” Biomaterials, vol. 30, pp. 5433-5444, 2009.
J. Kim, M. Junkin, D.H. Kim, S.L. Kwon, Y.S. Shin, P. K. Wong, and B. K. Gale, “Applications, techniques, and microfluidic interfacing for nanoscale biosensing,” Microfluidics and Nanofluidics, vol. 7, pp. 149-167, 2009.
D.H. Kim, J.Y. Park, K.Y. Suh, P. Kim, S.K. Choi. S.C. Ryu, S.H. Park, S.H. Lee and B. Kim, “Fabrication of patterned micromuscles with high activity for powering biohybrid microdevices”, Sensors and Actuators B, vol. 117, pp.391-400, 2006.
D.H. Kim, P. Kim, I.S. Song, J.M. Cha, S.H. Lee, B. Kim, and K.Y. Suh, “Guided three-dimensional growth of functional cardiomyocytes on polyethylene glycol nanostructures,” Langmuir, vol.22, no.12, pp.5419-5426, 2006.
E.S. Yoon, R.A. Singh, H.S. Kong, B. Kim, D.H. Kim, H.E. Jeong, and K.Y. Suh, “Tribological properties of bio-mimetic nano-patterned polymeric surfaces on silicon wafer,” Tribology Letters, vol.21, pp.31-37, 034303, 2006.
D.H. Kim, C.N. Hwang, Y. Sun, B. Kim, S.H. Lee, and B. Nelson, “Mechanical analysis of chorion softening in pre-hatching stages of zebrafish embryos,” IEEE Transactions on Nanobioscience, vol.5, no.2, pp.89-94, 2006.
P.N. Kim, D.H. Kim, B. Kim, S.K. Choi, S.H. Lee, A. Khademhosseini, R. Langer, and K.Y. Suh, “Fabrication of nanostructures of poly(ethylene glycol) for application to protein adsorption and cell adhesion,” Nanotechnology, vol.16, pp.2420-2426, 2005.
B. Kim, D.H. Kim, J.H. Jung, and J.O. Park, “A biomimetic undulatory tadpole robot using ionic polymer-metal composite actuators,” Smart Materials and Structures, vol. 14, pp.1579-1585, 2005.
D.H. Kim, M.G. Lee, B. Kim, and Y. Sun, “A superelastic alloy microgripper with embedded electromagnetic actuators and piezoelectric sensors: a numerical and experimental study,” Smart Materials and Structures, vol.14, pp.1265-1272, 2005.
D.H. Kim, Y. Sun, S. Yun, S.H. Lee, and B. Kim, “Investigating chorion softening of zebrafish embryos with a microrobotic force sensing system,” Journal of Biomechanics, vol.38, no.6, pp.1359-1363, 2005.
A. Haake, A. Neild, D.H. Kim, J.E. Ihm, Y. Sun, J. Dual, and B.K. Ju, “Manipulation of cells using an ultrasonic pressure field,” Ultrasound in Medicine and Biology, vol.31, no.6, pp.857-864, 2005.
D.H. Kim, B. Kim, and H.J. Kang, “Development of a piezoelectric polymer-based sensorized microgripper for micromanipulation and microassembly”, Microsystem Technologies, vol.10, no.4, pp.275-280, 2004.