Research Interest

Revealing native folding pathways for membrane proteins: My research group aims to understand how membrane proteins form their tertiary or quaternary structures. To answer this complex question, we employ a diverse array of single-molecule biophysics and cell biology tools to observe membrane protein folding in vitro as well as in cellular conditions, in unprecedented details. Before delving into this question, we have gained our experiences on how to apply single-molecule techniques to various membrane-involving biological processes. We have reported the disassembly mechanism of the SNARE complex by a proteasome system (20S complex) that provides important insights into how AAA+ ATPases tightly couple their ATP hydrolysis with unfolding of protein substrates (JACS 2013, Science 2015 and Nat. Comm. 2021). Our efforts finally culminate in a single-molecule approach based on magnetic tweezers, which permits observation of detailed folding pathways of multi-pass membrane proteins with a resolution of a few amino acids (Nat. Comm. 2013, 2014, 2018, Nat. Chem. Biol. 2015, Science 2019, and Nat. Chem. Biol. 2022). Our lab hopes to reveal the folding pathways of important human proteins, which may in turn shed lights into their evolutionary history, ER membrane protein homeostasis, and facilitation of folding of these membrane proteins for industrial applications.

Development of Tools for Precision Medicine: My research group is also interested in development of new single-molecule imaging tools. We recently developed single-molecule version of co-immunoprecipitation (co-IP) analysis (Nat. Comm. 2013, Nat. Prot. 2013). The co-IP analysis has been used as the gold standard of determining protein-protein interactions (PPIs) in the modern molecular biology for several decades. By adopting single-molecule fluorescence microscopy as the detection method (instead of SDS PAGE-gel and western blotting), we have improved the sensitivity and time-resolution of the co-IP analysis by five orders of magnitude, respectively. With the extreme sensitivity and quantitativeness of the developed tool, we demonstrate development of PPI biomarkers that allow precision prediction of drug responses of individual tumors, in particular, in cancer types without actionable genomic mutations. This suggests a path toward “personalized diagnosis of cancers at the PPI level”, which would expand the concept and scope of the targeted cancer therapy (Nat. Biomed. Eng. 2018, eLife 2020).

Professional Experience

• 2021.06 – National grant for leading scientists, Investigator
  National Research Foundation, South Korea
• 2020.03 – Seoul National University, Professor
  School of Biological Sciences
• 2017.03 – 2020.02 Seoul National University, Associate Professor
  School of Biological Sciences
• 2016. 03 – 2017.02 Yonsei University
  Yonsei-IBS Institute
• 2014. 02 – 2016.02 KAIST, Associate Professor with tenure
  Department of Physics
• 2014. 01 – 2018.02 Samsung Science and Technology Foundation, Principal Investigator
  Fundamental Sciences, Physics discipline
• 2011. 04 – 2020.02 National Creative Research Initiative, Principal Investigator
  Ministry of Science, ICT and Future Planning, South Korea
• 2010. 09 – 2014.02 KAIST, Associate Professor
  Department of Physics
• 2007. 10 – 2010.08 KAIST, Assistant Professor
  Department of Physics and KAIST Institute for the BioCentury
• 2006. 7 – 2007. 10 Howard Hughes Medical Institute, Research Associate
  University of Illinois, Urbana-Champaign
• 2005. 7 – 2006. 7 University of Illinois, Urbana-Champaign, Research Associate,
  Department of Physics
• 2004. 9 – 2005. 6 Seoul National University, Research Fellow
  Inter-University Semiconductor Research Center

Education

• 2000. 3 – 2004. 8 Seoul National University, Ph.D. in Electrical Engineering
  Thesis advisor: Prof. Sin-Doo Lee
  Thesis title: Control of Supramolecular Orderings by Patterned Surface
  Microstructures for Liquid Crystal Displays and Artificial Lipid Rafts
• 1998. 3 – 2000. 2 Seoul National University, M.S. in Electrical Engineering
• 1994. 3 – 1998. 2 Seoul National University, B.S. in Electrical Engineering

Honor & Awards

• 2022 Seoul National University Research and Teaching Awards (Research Discipline)
  (2022 서울대학교 학술연구교육상 (연구부문))
• Selected as Principal Investigator of the national grants for leading scientists endowed by National Research Foundation of South Korea (June, 2021)
  (2021 리더연구과제 책임자 선정, 막 단백질 단분자 연구단)
• 100 Outstanding Research Achievements of 2020 funded by the Korean government (2020년도 국가연구개발 우수성과 100선)
• Elected as a member of Young Korean Academy of Science and Technology (January, 2019) (한국차세대과학기술한림원)
• 2017 Kyung-Ahm Prize in Biological Sciences (September, 2017) (2017년도 경암상, 생명과학부문)
• Scientist of the Month, July 2017 awarded by the Ministry of Science, ICT and Future Planning
  (미래창조과학부 선정 2017년 7월, 이달의 과학자)
• 30 Young Scientists who will shine the future of South Korea (commemorated with the 30^th anniversary of the Pohang University of Science and Technology) (December 2016)
  (포항공대 개교 30주년 기념, 한국을 빛낼 젊은 과학자 30인)
• 2015 FILA Basic Science Award (awarded by the Korean Academy of Science and Technology) (November 2015)
  (제2회 FILA 기초과학상, 한국과학기술한림원)
• Blue Ribbon Lecture, Korean Society of Molecular and Cellular Biology (January, 2015)
  (한국분자세포생물학회 Blue Ribbon Lecture)
• Selected as Principal Investigator of Samsung Science and Technology Foundation (one of two recipients in the physics discipline), Samsung Science and Technology Foundation (November, 2013)
  (삼성미래기술육성재단 연구책임자 선정)
• Outstanding lecture award (2012 Fall Semester, Statistical Physics), College of Natural Science
  (2012 자연과학대학 우수강의 교원), KAIST (Feb. 2013)
• Outstanding research award, College of Natural Science
  (2012 자연과학대학 우수연구 교원), KAIST (December, 2012)
• 2011 100 Outstanding Research Achievements funded by the Korean government
  Selected as one of the Top 5 achievements, First placed in the basic science discipline
  (16개 범부처 국가연구개발 우수성과 100선, TOP5 선정, 기초연구부문 최우수성과)
• 2011 50 Outstanding Research Achievements funded by the Ministry of Education and Science of Korea
  (교육과학기술부 선정 기초연구 우수성과 50선)
• 2011 Selected as Principal Investigator of National Creative Research Initiative of Korea (April, 2011)
  (2011 창의적 연구진흥과제 선정, 단분자 시스템 생물학 연구단)
• Scientist of the Month, January 2011 awarded by the city of Daejeon
  (대전광역시 수여 이달의 과학기술인 상, 2011년 1월)
• Outstanding academic achievement award, 40th Anniversary of Foundation of KAIST
  (KAIST 개교 40주년 기념 학술상) (Feb. 16, 2011)

Selected Publications

• Hyun-Kyu Choi, Hyunook Kang, Chanwoo Lee, Hyun Gyu Kim, Ben P. Phillips, Soohyung Park, Charlotte Tumescheit, Sang Ah Kim, Hansol Lee, Soung-Hun Roh, Heedeok Hong, Martin Steinegger, Wonpil Im, Elizabeth A. Miller, Hee-Jung Choi and Tae-Young Yoon, Evolutionary balance between foldability and functionality of a glucose transporter, Nature Chemical Biology (18), 713-723.
• Hyun-Kyu Choi, Hyun Gyu Kim, Min Ju Shon, and Tae-Young Yoon, High-resolution single-molecule magnetic tweezers, Annual Review of Biochemistry (91), 33-59.
• Byoungsan Choi, Minkwon Cha, Gee Sung Eun, Dae Hee Lee, Seul Lee, Muhammad Ehsan, Pil Seok Chae, Won Do Heo, Yongkeun Park and Tae-Young Yoon (2020). Single-molecule functional anatomy of endogenous HER2-HER3 heterodimers, eLife(9), e53934.
• Hyun-Kyu Choi, Duyoung Min, Hyunook Kang, Min Ju Shon, Sang-Hyun Rah, Hak Chan Kim, Hawoong Jeong, Hee-Jung Choi, James U. Bowie and Tae-Young Yoon (2019). Watching helical membrane proteins fold reveals a common N- to C-terminal folding pathway. Science, 366(6469), 1150-1156.
• Min Ju Shon, Haesoo Kim, Tae-Young Yoon (2018). Focused clamping of a single neuronal SNARE complex by complexin under high mechanical tension. Nature Communications, 9(1), 3639.
• Lee, H. W., Choi, B., Kang, H. N., Kim, H., Min, A., Cha, M., … & Yun, M. R. (2018). “Profiling of protein–protein interactions via single-molecule techniques predicts the dependence of cancers on growth-factor receptors” Nature Biomedical Engineering, 2(4), 239.
• J.-K. Ryu, S. J. Kim, S.-H. Rah, J. I. Kang, H. E. Jung, D. Lee, H. K. Lee, J.-O. Lee, B. S. Park, T.-Y. Yoon, H. M. Kim (2017) “Reconstruction of LPS Transfer Cascade Reveals Structural Determinants within LBP, CD14, and TLR4-MD2 for Efficient LPS Recognition and Transfer” Immunity 46, 38-50
• D. Min, R. Jefferson, J. Bowie, & T.-Y. Yoon (2015) “Mapping the energy landscape for second-stage folding of a single membrane protein” Nature Chemical Biology 11, 981-987
• J.-K. Ryu, D. Min, S.-H. Rah, S. J. Kim, Y. Park, H. Kim, C. Hyeon, H. M. Kim, R. Jahn & T.-Y. Yoon (2015). Spring-loaded unraveling of a single SNARE complex by NSF in one round of ATP turnover. Science, 347(6229), 1485-1489.
• W. Bae, K. Kim, D. Min, J.-K. Ryu, C. Hyeon & T.-Y. Yoon (2014). Programmed folding of DNA origami structures through single-molecule force control. Nat. Commun., 5, 5654.
• H.-W. Lee, J. Ryu, J. Yoo, B. Choi, K. Kim & T.-Y. Yoon (2013). Real-time single-molecule co-immunoprecipitation of weak protein-protein interactions (Invited contribution). Nat. Protoc., 8(10), 2045-2060.
• W. Bae, M.-G. Choi, C. Hyeon, Y.-K. Shin & T.-Y. Yoon (2013). Real-Time Observation of Multiple-Protein Complex Formation with Single-Molecule FRET. J. Am. Chem. Soc., 135(28), 10254-10257.
• D. Min, K. Kim, C. Hyeon, Y. H. Cho, Y.-K. Shin & T.-Y. Yoon (2013). Mechanical unzipping and rezipping of a single SNARE complex reveals hysteresis as a force-generating mechanism. Nat. Commun., 4, 1705.
• H.-W. Lee, T. Kyung, J. Yoo, T. Kim, C. Chung, J. Y. Ryu, H. Lee, K. Park, S. Lee, W. D. Jones, D.-S. Lim, C. Hyeon, W. D. Heo & T.-Y. Yoon (2013). Real-time single-molecule co-immunoprecipitation analyses reveal cancer-specific Ras signalling dynamics. Nat. Commun., 4, 1515.
• H.-K. Lee, Y. Yang, Z. Su, C. Hyeon, T.-S. Lee, H.-W. Lee, D.-H. Kweon, Y.-K. Shin & T.-Y. Yoon (2010). Dynamic Ca2+-Dependent Stimulation of Vesicle Fusion by Membrane-Anchored Synaptotagmin 1. Science, 328(5979), 760-763.

Selected Presentations (since 2013)

• Plenary lecture at 18th Biophysics Conference and Annual Meeting of the Biophysics Society of ROC (Academia Sinica, Taipei, June 29, 2013)
• Invited talk at Frontiers in Membrane Protein Structural Dynamics 2014 (University of Chicago, May 7, 2014)
• Invited talk at Gordon Research Conference on Single-Molecule Approaches to Biology (Lucca, July 14, 2014)
• Invited talk, Frontier in Biological Science Seminar series (Tsinghua University, Beijing, Oct. 8, 2014)
• Invited talk, Blue Ribbon Lecture of Korean Society of Molecular and Cellular Biology (January 22, 2015)
• Invited talk, Yonsei Nobel Forum 2015 for Dr. Randy W. Schekman (May 28, 2015)
• Invited talk, Inaugural Gordon Research Conference on Membrane Protein Folding (Bentley University, Waltham, USA, June 21-26, 2015)
• Invited talk, DGIST Global Innovation Festival (DGIF) 2015 (November 19, 2015)
• Plenary talk, 2016 Annual Meeting of Korean Society for Structural Biology (July 4, 2016)
• Invited talk, Third International Symposium on Protein Folding and Dynamics (November 10, 2016, Bangalore, India)
• Organizer, 1st Korea-Japan Joint Symposium on Single-Molecule Biophysics (November 26, 2016, Tsukuba, Japan)
• Invited talk, 31^st Annual Symposium of the Protein Society (to be July 24-27, 2017, Montreal, Canada)
• Organizer, 2^nd Korea-Japan Joint Symposium on Single-Molecule Biophysics (November 9, 2017, SNU)
• Organizer, Focused Symposium on Molecular Mechanisms of Membrane Trafficking (May 17-19, 2018, SNU)
• Organizer, 1^st East Asian Symposium on Single-Molecule Biological Sciences (September 23-25, 2018, Okayama Japan)
• Organizer, 2nd East Asian Symposium on Single-Molecule Biological Sciences (July 25-27, 2019, SNU)
• Invited talk, 3rd Annual Conference on Protein Folding on The Ribosome (December 14-16, 2019 in Berlin, Germany)
• Plenary talk, Annual Meeting of the Biophysics Division, Korean Physical Society (January 25-26, 2022)
• Invited talk, 2022 Biomembranes meeting (September 15-17, 2022 in Bangalore, India; online presentation)
• Organizer, Inter-Academy Workshop (February 6-7, 2023, Stockholm, Sweden; Supported by the South Korean NAS)
• Invited talk, 37^th Annual Symposium of the Protein Society (July 13-16, 2023, Boston, USA)