Hee-Sun Han

 Hee-Sun Han

Contact Information

47 RAL, Box 47-5
Department of Chemistry
University of Illinois
600 South Mathews Ave.
Urbana, IL 61801
Assistant Professor of Chemistry, Mark A. Pytosh Scholar

Biography

Professor Han obtained her B.S. degree in Chemistry from the College of Natural Sciences at Seoul National University, Korea, where she graduated summa cum laude and Valedictorian in 2006. After college, she moved to Cambridge, USA to pursue graduate work in Physical Chemistry at MIT as a Samsung and KASF fellow. Under the guidance of Prof. Moungi G. Bawendi, she designed and synthesized new quantum dot based imaging probes and developed a multiplexed, phenotypic, intravital cytometric imaging platform. She then moved to Harvard to work with Prof. David A. Weitz as a postdoctoral fellow. At Harvard, she pioneered drop-based microfluidic platforms for high throughput sequencing of single viruses. She joined the University of Illinois faculty as the Mark A. Pytosh Scholar and Assistant Professor in Fall 2017. Her group leverage advances in nanotechnology, in vivo imaging, and microfluidics to pioneer broadly applicable platforms for studying single cells at high throughput in context of their environments. 

Research Interests

  • Dissecting complex molecular networks in healthy/diseased tissues, Single cell omics, Single virus genomics, In vitro/in vivo imaging, Quantum dots, Microfluidics, High-throughput technologies

Research Description

We develop novel technologies integrating diverse chemical and physical principles to study intact, fully assembled biological systems with single cell/molecule resolution, at high throughput while retaining the spatial or environmental information of each cells in vivo. Intact organs are complex systems comprising highly heterogeneous cell populations that interact intensively with each other and with neighboring environments. Recent development of single cell sequencing technologies enables researchers to characterize the genomic/transcriptomic profile of individual cells and to identify rare cell populations that may play a key role in determining the fate of an organ. However, most current single cell sequencing techniques involve disaggregation of tissues; therefore, it is still very challenging to correlate the spatial and environmental information of cells in vivo to their transcriptomic profiles. The cellular heterogeneity data alone does not provide enough information to decipher the molecular and cellular mechanisms underlying the function or dysfunction of an organ as the interplay of cells among themselves or with neighboring environments often govern the overall function. We leverage advances in nanotechnology, materials chemistry, bio-imaging, and drop-based microfluidics to pioneer technologies for correlating single cell sequencing data with the structural, molecular and environmental characteristics of intact organs. This approach allows us to assess how the molecular profile of individual cells are spatially organized throughput a tissue and to analyze how the extra-cellular environments of cells influence their RNA profiles and, ultimately, the function of the complete organ.

Microfluidic platforms developed for high throughput single cell can also be used for single virus genomics studies. Viruses have enormous impact on human lives, not only by causing diseases, but also by shaping our immune systems. Despite their ubiquity and influence, less than 0.01% of viral species have been identified and studied. The main challenge for sequencing novel viruses is the requirement for establishing cultivable virus-host systems. Ability to sequence viral genomes from a single virion eliminate the needs for cell culture and open a wide door to novel virus discovery. Whole genome sequence data produced from uncultivable viruses will promote new investigations into viral ecology, evolutionary biology, epidemiology and other clinical sciences and identification of single virus mutations will facilitate our understanding on virus evolution and adaptation.

Following are the main technologies we use in the lab:

Intravital  (in vivo) imaging

Imaging live animals at microscopic resolution, intravital imaging, allows researchers to directly study how cells are spatially organized, move, interact with each other and respond to pathological stimuli in their native states. We develop intravital imaging methods to probe the extra cellular environments of cells in  vivo and record that information so that we can correlate the in vivo characteristics of cells with their molecular profiling.

Quantum  dot probes for bioimaging

Semiconductor nanocrystals, known as quantum dots (QDs), exhibit optimal properties for bioimaging applications: tunable bandgap, high molar extinction coefficients, broad absorption, superior photostability than dyes, narrow (25-35 nm) and Gaussian-shaped emission profiles, etc. We synthesize high quality core-shell QDs emitting in visible to near infrared and new surface coatings for QDs to prepare bright, compact, stable, and biocompatible QD probes for in vitro and in vivo imaging.

Drop-based  Microfluidics for single cell/virus studies

Drop-based microfluidic offers the perfect platform for high-throughput molecular profiling of single-cells or viruses, owing to its scalability and high-throughput ability. In this technology, individual cells or viruses are compartmentalized into monodisperse, micron-sized droplets, which function as independent reaction vessels. The low volume of drops enables production of ten million drops from 100 µL-1 mL samples, yields high reaction efficiency, and ensures fast reaction time and low cost. Drops can be manipulated at the rate of 1000-30,000 Hz to add and subtract reagents allowing multi-step reactions.  In addition, capture efficiency is high since all cells or viruses in a sample volume can be captured in drops. We combine drop-based microfluidics, materials chemistry, and various sorting technologies to develop new single cell/virus sequencing platforms.

Education

  • Massachusetts Institute of Technology: Ph.D. in Physical Chemistry
  • Seoul National University: B.S. in Chemistry

Distinctions / Awards

  • Mark A. Pytosh Scholar 2017-
  • Morse Travel Grant 2011
  • KFAS Scholarship for Ph.D. Studies 2006-2012
  • Samsung Scholarship for Ph.D. Studies 2006-2011
  • Valedictorian, Summa Cum Laude, Seoul National University 2006
  • Representative of Korea in Lindau Nobel Laureate Meeting 2006
  • KFAS Scholarship for outstanding undergraduate students 2004-2006
  • Merit Based Scholarship, Seoul National University, 2002-2006

Courses

  • Chem 520: Advanced Analytical Chemistry

Selected Publications

Journal Articles

Han, H.-S, A. Rotem, S. K. Cockrell, M. Carbonnaux, J. M. Pipas, and D. A. Weitz Whole-Genome Sequencing of a Single Viral Species from a Highly Heterogeneous Sample Angew. Chem. Int. Ed. 54 2015, p. 13985-13988.
Han, H.-S, E. Niemeyer, Y. Huang, W. S. Kamoun, J. D. Martin, J. Bhaumik, Y. Chen, S. Roberge, J. Cui, M. R. Martin, D. Fukumura, R. K. Jain, M. G. Bawendi, and D. G. Duda Quantum Dot/Antibody Conjugates for In vivo Cytometric Imaging in Mice Proc. Natl. Acad. Sci. U.S.A. 112 2015, p. 1350-1355.
Chen, O, J. Zhao, V. P. Chauhan, J. Cui, C. Wong, D. K. Harris, H. Wei, H.-S Han, D. Fukumura, R. K. Jain, and M. G. Bawendi Compact High-Quality CdSe-CdS Core-Shell Nanocrystals with Narrow Emission Linewidths and Suppressed blinking Nat. Mater. 12 2013, p. 445-451.
Han, H.-S, J. Martin, J. Lee, D. K. Harris, D. Fukumura, R. K. Jain, and M. G. Bawendi Spatial Charge Configuration Regulates Nanoparticle Transport and Binding Behavior in vivo Angew. Chem. Int. Ed. 52 2013, p. 1414-1419.
Wei, H, N. Insin, J. Lee, H.-S. Han, J. M. Cordero, W. Liu, and M. G. Bawendi Compact Zwitterion-Coated Iron Oxide Nanoparticles for Biological Applications Nano Lett. 12 2012, p. 22-25.
Harris, D. K, P. M. Allen, H.-S. Han, B. J. Walker, J. Lee, and M. G. Bawendi Synthesis of Cadmium Arsenide Quantum Dots Luminescent in the Infrared J. Am. Chem. Soc. 133 2011, p. 4676-4679.
Han, H.-S, N. K. Devaraj, J. Lee, S. A. Hilderbrand, R. Weissleder, and M. G. Bawendi Development of a Bioorthogonal and Highly Efficient Conjugation Method for Quantum Dots using Tetrazine-Norbornene Cycloaddition J. Am. Chem. Soc. 132 2010, p. 7838-7839.