(3c) In Vivo Multiplexed Nanoengineering for Assessing Biological Heterogeneity

Research Interests: My research group aims at developing a nanotechnology-based toolbox for multiplexed assessment to the diverse components of heterogeneous biological systems for accurate diagnosis and patient-specific therapeutic decisions. Since the expression of the heterogeneity is most prominent in living subjects, we will (i) construct multicolor-coded nanoparticle imaging probes and (ii) conduct a noninvasive and multiplexed imaging to monitor multiple biological targets at the single cellular level in vivo. Among the biological models of heterogeneity with multiple targets, we particularly aim to monitor tumor biomarkers with multiple immune components to understand immunotherapeutic response in the context of tumor heterogeneity. In this regard, (iii) we will also study nanoparticles-immune interaction by actively modulating the multiple immune components. This research topic is of particular importance as the nanoparticle-immune interaction governs nanoparticle delivery into tumors and clearance of nanoparticles, both of which are critical for the translation of nanomedicine. Our research program will not only create a novel tool for multiplexed assessment to living subjects, but also cultivate a fundamental understanding of how the nanoparticles interact with biological systems in vivo.

Research Experiences: During my Ph.D years (Prof. Taeghwan Hyeon, Chemical and Biological Engineering, Seoul National University), I worked on colloidal semiconductor nanocrystal quantum dots, of which the research field has created multi-billion dollar component market through commercialization of quantum dot color TV. I studied the smallest atomic cluster units of the nanocrystal quantum dots ((CdSe)₁₃) and found out their selective chemical reaction of incorporating magnetic ions to generate giant magneto-optical response¹. I also worked on biocompatible nanophosphor, zinc sulfide (ZnS), which was used for cathode-ray tube display. Instead of the color display application, I studied nonlinear optics of the ZnS phosphor nanoparticles, i.e., three-photon phosphorescence, and utilized the nanoparticles for the multiphoton bioimaging application^2,3.

After my postdoc training, when I worked on two-dimensional layered materials for energy applications (Prof. Yi Cui, Materials Science & Engineering, Stanford University)⁴, I joined Stanford School of Medicine strongly motivated by biomedical research (Prof. Sanjiv Sam Gambhir, School of Medicine, Stanford University). Currently, the clinical imaging provides images of anatomy and expression of one or two biomarkers, which look like black-and-white displays. I was motivated by the necessity to develop a multiplexed imaging method, which visualizes biological structures in all their complexity as multi-color-coded displays. In this regard, I created multispectral surface-enhanced Raman scattering (SERS) nanoparticles and successfully performed five-color imaging of the nanoparticles-targeting tumors in living mice⁵, which will lay the foundation for my future research as an independent tenure-track professor.

Teaching Interests: With my training in chemical engineering, nanotechnology, and materials science, I can teach most of the undergraduate courses in these classes. I am particularly interested in how to motivate students to solve “outside of the field problems” through the understanding of basic chemical engineering principles. The first example is a semiconductor processing class, in which transport phenomena and chemical reaction engineering concepts can be applied to optimize non-classical chemical processes, such as electronics processing. The second example is in vivo nanoparticle drug delivery, in which nanoparticle delivery in tumors can be understood with the mass transport equations.

At Stanford University, I mentored several undergraduate research interns and graduate researchers of diverse backgrounds and ethnicity. I also served as a guest lecturer in an undergraduate course “Chem 26N: The What, Why, How, and Wow’s of Nanotechnology.” I will build a strong educational program to motivate next-generation chemical engineers of diverse backgrounds to solve interdisciplinary problems outside their boxes.

Selected Publications:

1. J.H. Yu, X. Liu, K. E. Kweon, J. Joo, J. Park, K.-T. Ko, D.W. Lee, S. Shen, K. Tivakornsasithorn, J.S. Son, J.-H. Park, Y.-W. Kim, G. S. Hwang, M. Dobrowolska, J.K. Furdyna, and T.Hyeon, “Giant Zeeman Splitting in Nucleation-Controlled Doped CdSe:Mn²⁺ Quantum Nanoribbons.” Nat. Mater.2010, 9, 47-53.
2. J.H. Yu, S.-H. Kwon, Z. Petrášek, O.K. Park, S.W. Jun, K. Shin, M. Choi, Y.I. Park, K. Park, H.B. Na, N. Lee, D.W. Lee, J.H. Kim, P. Schwille, and T. Hyeon, “High-resolution three-photon biomedical imaging using doped ZnS nanocrystals.” Nat. Mater. 2013, 12, 359-366.
   (see also “Bioimaging: Illuminating the deep.”Nat. Mater. 2013,12, 285-287. (News and Views))
3. J.H. Yu, J. Kim, T. Hyeon, and J. Yang “Facile synthesis of manganese (II)-doped ZnSe nanocrystals with controlled dimensionality.” J. Chem. Phys. 2019, 151, 244701.
4. J.H. Yu, H.R. Lee, S.S. Hong, D. Kong, H.-W. Lee, H. Wang, F. Xiong, S. Wang, and Y. Cui, “Vertical Heterostructure of MoS₂ and WSe₂ with Vertically Aligned Layers.” Nano Lett. 2015, 15,1031-1035.
5. J.H. Yu, I. Stenberg, R.M. Davis, A.V. Malkovskiy, A. Zlitni, L.D. Curet, K.o. Jung, D.T. Chung, A.L. D’Souza, E. Chang, J. Campbell, J. Frostig, S.-m. Park, G. Pratx, and S.S. Gambhir, “Noninvasive and Highly Multiplexed Five-Color Tumor Imaging of Near-Infrared Resonant Surface-Enhanced Raman Nanoparticles In Vivo” 2020, submitted.