 |
| Born
Guizhou, P. R. China, 1972. |
| University
of Science and Technology of China (USTC), B.S., 1994. |
| Massachusetts
Institute of Technology, Ph.D., 2000. |
| Harvard
University, Postdoctoral Fellow, 2000-2002. |
University
of Chicago,
Assistant Professor 2002-2008.
Associate Professor 2008-. |
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| Accolades |
| 2008
Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious
Disease Award. |
| 2007
CACPA Distinguished Junior Faculty Award. |
| 2006
Camille Dreyfus Teacher-Scholar Award. |
| 2005
CAREER Award from the National Science Foundation. |
| 2005
Cottrell Scholar by the Research Corporation. |
| 2005
Arnold and Mabel Beckman Foundation Young Investigator. |
| 2005
Alfred P. Sloan Research Fellowship. |
| 2004
W. M. Keck Foundation Distinguished Young Scholar in Medical Science. |
| 2004
G&P Foundation for Cancer Research Young Investigator. |
| 2003
Research Corporation Research Innovation Award. |
| 2003
Searle Scholar Award. |
| 2001
Davison Prize for The Best Thesis in Inorganic Chemistry, MIT. |
| 2000-2002
Damon Runyon-Walter Winchell Cancer Research Fund Postdoctoral Fellow
(Harvard). |
| 1997-1999
Merck/MIT Graduate Fellowship. |
| Guest Professor, University of Science and Technology of
China (USTC).
|
| Joint Professor, Peking University.
|
|
|
| Chuan He |
| Associate
Professor |
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| Research
Interests |
|
Our research program spans a broad range of chemistry, chemical biology, microbiology, bioinorganic chemistry, cell biology and structural biology. We probe the pathways and mechanisms of DNA/RNA repair and modification. We work on virulence and antibiotic resistance regulation in human pathogens, and develop new antibiotics. We study selective metal ion recognition and sensing by naturally occurring and engineered proteins. We also explore metal-catalyzed organic transformations. |
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| 1.
DNA/RNA Repair and Modification |
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Accumulation of genetic changes due to the presence of unrepaired DNA lesions can lead to cancer and other diseases. One component of our research program is to develop and apply a novel chemical cross-linking technique to stabilize protein-DNA interactions in distinct states in these systems. An integrative approach uniting chemical synthesis, structural biology and biochemical/biophysical characterization is used to study these interactions in DNA/RNA repair AlkB family proteins and other DNA/RNA base repair and modification proteins. In a related component of the research, we work on elucidating new pathways and mechanisms involved in DNA and RNA base modification with a focus on methylation and demethylation.
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| 2.
Virulence and Antibiotic Resistance Regulation in Human Pathogens |
| Staphylococcus
aureus and Pseudomonas aeruginosa are
human pathogens responsible for most wound and hospital-acquired
infections. The extensive use of antibiotics to treat infections has
led to the emergence of high-level resistances in various strains of
these pathogens. Virulence suppression provides an alternative strategy
to effectively reduce pathogenic potential without asserting selective
pressure for developing resistances. A recent discovery in our
laboratory has identified the MgrA protein as a key virulence regulator
in S. aureus. This protein belongs to the MarR
family of transcriptional regulators that controls antibiotic
resistance and virulence in various bacteria. We demonstrated that the mgrA
knockout strain shows a 10,000-fold reduction of virulence in vivo.
Subsequently, we discovered that oxidative stress leads to dissociation
of MgrA from its promoter DNA. The host immune response to S.
aureus infection is to produce reactive oxygen and nitrogen
species to counter the pathogen. Our study suggests that the
microorganism uses MgrA to sense the oxidative stress generated by the
host and regulate a global defensive response. We plan to fully
elucidate the mechanism of MgrA and its regulation pathways, and
exploring several strategies to suppress S. aureus
virulence by tuning MgrA’s function with small molecules. In
addition, we are studying MgrA homologues in S. aureus,
P. aeruginosa and
other pathogens. Our ultimate goal is to develop new strategies for
treating infections. . |
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| 3. Selective Metal Ion Recognition by Proteins |
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The ability to regulate essential or toxic metal ion concentrations is critical for cell survival. Our goal is to understand how specific metal ions are recognized and regulated in biological systems. We have been working on elucidating the mechanisms of proteins that exhibit remarkable selectivity toward metal ions such as lead(II), cadmium(II), gold(I), copper(I) and iron(II). Some of these proteins can be converted into genetically encoded fluorescent probes for sub-cellular metal ion imaging in live cell. We also work on engineering proteins that possess high sensitivity and selectivity toward various metal ions including actinides. |
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| 4. Catalysis |
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We study the fundamental activity of metal complexes and develop new organic transformations. Currently, our group is focusing on direct functionalization of inert C-H groups and activation of inert small molecules with metal catalysts.
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| Selected
References |
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Yang, C.-G.; Yi, C.; Duguid, E. M.; Sullivan, C. T.;
Jian, X.; Rice, P. A. and He, C.* “Crystal Structures of DNA-RNA Repair Enzymes AlkB and ABH2 Bound to dsDNA” Nature, 2008, 452, 961-965.
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Chen, P.; Bae, T.; Williams,
W. A.; Duguid, E. M.; Rice, P. A.; Schneewind, O. and He, C.* “An Oxidation
Sensing Mechanism is Used by A Global Regulator of Staphylococcus aureus” Nature
Chem. Biol. 2006, 2, 591-595.
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Chen, H.; Hu, J.; Chen, P.
R.; Lan, L.; Li, Z.; Hicks, L. M.; Dinner, A. R. and He, C.* “The Pseudomonas aeruginosa Multidrug Efflux
Regulator MexR Uses An Oxidation Sensing Mechanism” Proc. Natl. Acad. Sci. 2008, 105,
13586-13591.
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| Chen, C.-S.; Karabkova,
E.; Chen, H.; Jian, X.; Zhu, J.; Tao, S.-C.; Hu, S.; He, C.* and Zhu, H.* “A
Proteome Chip Approach Reveals New DNA
Base Damage Recognition Activities in Escherichia coli” Nature
Methods, 2008, 5, 69-74. |
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Chen, P. R. and He, C.*
“Selective Recognition of Metal Ions by Metalloregulatory Proteins” Curr. Opin.
Chem. Biol. 2008, 12, 214-221.
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Li,
Z.; Capretto, D. A. and He, C.* “Gold Catalyzed Organic Transformations” Chem. Rev. 2008, 108, 3239-3265.
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Inorganic Chemistry 