个人简介
Professional
2013-present Professor and Canada Research Chair (University of British Columbia)
2009-2013 Associate Professor and Canada Research Chair (University of British Columbia)
2004-2009 Assistant Professor and Canada Research Chair(University of British Columbia)
2002-2004 Associate Research Scientist (Columbia University, USA)
Education
1999-2002 Research Fellow (Mayo Medical Center, USA, Advisor: Prof. Julio M. Fernandez)
1993-1998 Ph.D. (Polymer Chemistry and Physics at Jilin University, China, Advisors: Profs. Jiacong Shen, Xi Zhang and Hermann E. Gaub)
1996-1997 Visiting PhD student (Ludwig-Maximilians-Universität München, Germany, Advisor: Prof. Hermann E. Gaub)
1989-1993 B.Sc (Polymer Engineering, Tianjin University, China)
Awards
2012 Changjiang Guest Chair Professorship (Jilin University, China)
2011 JILA Visiting Fellowship (JILA and University of Colorado, Boulder)
2011 Alexander von Humboldt Fellowship (Technical University of Munich, Germany)
2010 JILA Distinguished Short-term Visiting Fellow (JILA and University of Colorado, Boulder)
2010 Charles McDowell Award for Research (UBC)
2006 Michael Smith Foundation for Health Research Career Investigator Award
2005 Peter Wall Institute for Advanced Studies Early Career Award (UBC)
研究领域
Analytical Chemistry; Biological & Medicinal Chemistry; Materials & Polymer Chemistry; Physical & Theoretical Chemistry
Our research program is in the area of single molecule biophysical chemistry. We are interested in the mechanical properties and conformational dynamics of elastic proteins. Elastic proteins are important structural and functional components in living cells. They serve as molecular springs in tissues to establish elastic connections and provide mechanical strength, elasticity, and extensibility. They are not only important for their biological functions in various biological processes, but also important building blocks for bottom-up construction of smart materials and mechanical devices on the nanoscale.
Our main research tool is single molecule atomic force microscopy. The AFM is a powerful technique allowing us to directly manipulate proteins one molecule at a time. We use the AFM to measure the mechanical properties of proteins, and monitor the folding/unfolding trajectories of single protein in real time. Our long term goal is to understand the mechanical properties of proteins at the single molecule level and use protein engineering techniques to design proteins with tailored mechanical properties to be used as functional and structural components for smart materials and nanomechanical devices.
Research directions
1. Protein Mechanics and Engineering: combining protein engineering with single molecule AFM and computation, we rationally design and engineer proteins with tailored mechanical properties.
Representative publications:
J. Am. Chem. Soc. 2012, 134, 4124-4131.
Acc. Chem. Res. 2010, 43, 1331-1341.
J. Am. Chem. Soc. 2009, 131,14050-14056.
Proc. Nat. Acad. Sci. USA, 2008, 105, 11152-11157.
Nature Nanotechnology, 2008, 3, 512-516.
2. Single Protein Folding/Unfolding Dynamics: we use single molecule force spectroscopy techniques to investigate the folding/unfolding dynamics and mechanism of proteins at the single molecule level.
Representative publications:
Proc. Nat. Acad. Sci. USA, 2013, 110, 18156-18161.
J. Am. Chem. Soc. 2013, 135, 7992-8000.
BIOPHYSICAL JOURNAL 2012, 103, 807-816.
J. Am. Chem. Soc. 2012, 134, 10428-10435.
J. Am. Chem. Soc. 2009, 131, 13347-13354.
Proc. Nat. Acad. Sci. USA, 2008, 105, 1885-1890.
3. Protein-based Biomaterials: using the knowledge from protein mechanics studies, we rationally design protein-based biomaterials with tailored mechanical properties for various biomedical applications. We rationally tailor macroscopic mechanical properties of these biomaterials by programming the molecular sequence, and thus nanomechanical properties, of protein building blocks at the single-molecule level.
Representative publications:
Nature 2010, 465, 69 – 73.
Nature Communications 2013, 4.
Acta Biomaterialia 2013, 9, 6481-6491.
Langmuir 2012, 28, 2269-2274
Chem. Commun. 2008, 4144-4146.
4. Polymer physical chemistry using single molecule AFM: we use single molecule AFM to investigate the conformational change of polymers at the singel molecule level.
5. AFM imaing of biological materials
近期论文
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"Wang, Y. Y. ; Hu, X. ; Bu, T. ; Hu, C. ; Hu, X. ; Li, H. Molecular Calipers For Highly Precise And Accurate Measurements Of Single-Protein Mechanics. Langmuir 2014, 30, 2761-2767.BibTex
Lamour, G. ; Yip, C. K. ; Li, H. ; Gsponer, J. High Intrinsic Mechanical Flexibility Of Mouse Prion Nanofibrils Revealed By Measurements Of Axial And Radial Young's Moduli. ACS Nano 2014, In press.BibTex
Bull, M. S. ; Sullan, R. M. ; Li, H. ; Perkins, T. T. Mproved Single Molecule Force Spectroscopy Using Micromachined Cantilevers. ACS Nano 2014, In press.BibTex
Panwar, P. ; Du, X. ; Sharma, V. ; Lamour, G. ; Castro, M. ; Li, H. ; Broemme, D. Effects Of Cysteine Proteases On The Structural And Mechanical Properties Of Collagen Fibers. JOURNAL OF BIOLOGICAL CHEMISTRY 2013, 288, 5940-5950.BibTex
Fang, J. ; Mehlich, A. ; Koga, N. ; Huang, J. ; Koga, R. ; Gao, X. ; Hu, C. ; Jin, C. ; Rief, M. ; Kast, J. ; Baker, D. ; Li, H. Forced Protein Unfolding Leads To Highly Elastic And Tough Protein Hydrogels. Nature Communications 2013, 4.BibTex
Zoldak, G. ; Stigler, J. ; Pelz, B. ; Li, H. ; Rief, M. Ultrafast Folding Kinetics And Cooperativity Of Villin Headpiece In Single-Molecule Force Spectroscopy. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2013, 110, 18156-18161.BibTex
Ostapchenko, V. G. ; Beraldo, F. H. ; Mohammad, A. H. ; Xie, Y. - F. ; Hirata, P. H. F. ; Magalhaes, A. C. ; Lamour, G. ; Li, H. ; Maciejewski, A. ; Belrose, J. C. ; Teixeira, B. L. ; Fahnestock, M. ; Ferreira, S. T. ; Cashman, N. R. ; Hajj, G. N. M. ; Jackson, M. F. ; Choy, W. - Y. ; MacDonald, J. F. ; Martins, V. R. ; Prado, V. F. ; Prado, M. A. M. The Prion Protein Ligand, Stress-Inducible Phosphoprotein 1, Regulates Amyloid-Beta Oligomer Toxicity. JOURNAL OF NEUROSCIENCE 2013, 33, 16552-16564.BibTex
Bai, Y. ; Luo, Q. ; Zhang, W. ; Miao, L. ; Xu, J. ; Li, H. ; Liu, J. Highly Ordered Protein Nanorings Designed By Accurate Control Of Glutathione S-Transferase Self-Assembly. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2013, 135, 10966-10969.BibTex
Zheng, P. ; Takayama, S. -ichiJ. ; A. Mauk, G. ; Li, H. Single Molecule Force Spectroscopy Reveals That Iron Is Released From The Active Site Of Rubredoxin By A Stochastic Mechanism. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2013, 135, 7992-8000.BibTex
Lv, S. ; Bu, T. ; Kayser, J. ; Bausch, A. ; Li, H. Towards Constructing Extracellular Matrix-Mimetic Hydrogels: An Elastic Hydrogel Constructed From Tandem Modular Proteins Containing Tenascin Fniii Domains. ACTA BIOMATERIALIA 2013, 9, 6481-6491.BibTex
Li, Y. Devin; Lamour, G. ; Gsponer, J. ; Zheng, P. ; Li, H. The Molecular Mechanism Underlying Mechanical Anisotropy Of The Protein Gb1. BIOPHYSICAL JOURNAL 2012, 103, 2361-2368.BibTex
Shen, T. ; Cao, Y. ; Zhuang, S. ; Li, H. Engineered Bi-Histidine Metal Chelation Sites Map The Structure Of The Mechanical Unfolding Transition State Of An Elastomeric Protein Domain Gb1. BIOPHYSICAL JOURNAL 2012, 103, 807-816.BibTex
Bu, T. ; Wang, H. - C. Eileen; Li, H. Single Molecule Force Spectroscopy Reveals Critical Roles Of Hydrophobic Core Packing In Determining The Mechanical Stability Of Protein Gb1. LANGMUIR 2012, 28, 12319-12325.BibTex
Peng, Q. ; Kong, N. ; Wang, H. - C. Eileen; Li, H. Designing Redox Potential-Controlled Protein Switches Based On Mutually Exclusive Proteins. PROTEIN SCIENCE 2012, 21, 1222-1230.BibTex
He, C. ; Genchev, G. Z. ; Lu, H. ; Li, H. Mechanically Untying A Protein Slipknot: Multiple Pathways Revealed By Force Spectroscopy And Steered Molecular Dynamics Simulations. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2012, 134, 10428-10435.BibTex
Fang, J. ; Li, H. A Facile Way To Tune Mechanical Properties Of Artificial Elastomeric Proteins-Based Hydrogels. LANGMUIR 2012, 28, 8260-8265.BibTex
Zheng, P. ; Takayama, S. -ichiJ. ; A. Mauk, G. ; Li, H. Hydrogen Bond Strength Modulates The Mechanical Strength Of Ferric-Thiolate Bonds In Rubredoxin. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2012, 134, 4124-4131.BibTex
Lv, S. ; Cao, Y. ; Li, H. Tandem Modular Protein-Based Hydrogels Constructed Using A Novel Two-Component Approach. LANGMUIR 2012, 28, 2269-2274.BibTex
Cao, Y. ; Li, H. Single-Molecule Force-Clamp Spectroscopy: Dwell Time Analysis And Practical Considerations. LANGMUIR 2011, 27, 1440-1447.BibTex
Aioanei, D. ; Lv, S. ; Tessari, I. ; Rampioni, A. ; Bubacco, L. ; Li, H. ; Samori, B. ; Brucale, M. Single-Molecule-Level Evidence For The Osmophobic Effect. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 2011, 50, 4394-4397.BibTex