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Huang Chaolan

  

Wong, Catherine CL

The Introduction of Outstanding Talents for Technology, CAS

PIAssociate Professor with tenured

Peking University School of Pharmaceutical Science (PKUSPS)

Peking University First Hospital

Director, Center for Precision Medicine MultiOmics Research, PKUHSC (CPMMOR, PKUHSC)

Research Area

Mass spectrometry

MultiOmics technology

 

Education & Positions

B.S. in Chemistry/Sociology, Chinese University of Hong Kong, China, 1990-1994.

M.S. in Chemistry, The University of Hong Kong, China, 1996-1998.

Ph.D. in Chemistry, The University of Hong Kong, China, 2000-2003.

Research Associate, Chi-ming Che Lab, Dept. of Chemistry, the University of Hong Kong, China, 1/2004 – 4/2005.

Postdoctoral Fellow, John R Yates III Lab, The Scripps Research Institute (TSRI), La Jolla, CA, USA, 4/2005 – 12/2007.

Senior Staff Scientist/Lab Manager, John R Yates III Lab, The Scripps Research Institute (TSRI), La Jolla, CA, USA, 1/2008 – 1/2013.

Principal Investigator/Professor, Head of Mass Spectrometry Division, National Center for Protein Science, Shanghai, SIBCB, CAS, 1/2013 – 6/2017.

Principal Investigator/Associate Professor with Tenure, Director of Center for Precision Medicine MultiOmics Research, PKUHSC (CPMMOR, PKUHSC), 7/2017 – Present.

 

Faculty Accolades

Outstanding Introduction Technological Talent Award of Chinese Academy of Science, 2014.

Pilot B Project Grant, 2014.

Hong Kong Society of Mass Spectrometry Travel Award, 2002.

Postgraduate Scholarship, Dept. of Chemistry, the University of Hong Kong, 2000 – 2002.

Sir Edward Youde Memorial Prizes Scholars, Hong Kong, 1990.

 

Research Interests

Research Highlights

●  The first direct identification of arginylation regulated by ATE gene in vivo and its substrate of Beta-actin. This reveals how it regulate the properties of beta-actin in dynamic cell, especially it provides a new finding of its function in cardiovascular disease and angiogenesis on the molecular level. The paper drew a wide attention in the field. (Science, 2006) Further, with the self-developed antibody, firstly identified and verified total 43 in vivo substrates of protein arginylation and the accurate specific modified sites. It reveals its cardiovascular regulation processes involving in the development and growth of blood vessels. It influences on the stability of metabolism, especially in the skeleton and regulation cell migration as well as other functions. The discovery fills up the blank and opens up the whole research field of arginylation. (PLoS Biology, 2007; Nature Protocol, 2009; and many others…) .

●  Developed innovative methods of identification of 297 accurate sites of phosphorylation of 18 centrosome protein complexes of yeast cell cycle. Established an in-depth system and depicted a comprehensive of phosphor proteome in yeast cell cycle centrosome complex. Provided this field a complete and precious resource for further studies. (Science, 2011).

●  The first direct identification of a very labile modification – protein nitrosolation (NO) using innovated electron transferred dissociation with top-down analysis method, thus reveal the X-chain apoptosis inhibiting protein (XIAP) regulation depends on caspase mechanism of nerve cell apoptosis. (Molecular Cell, 2010).

●  Comprehensively optimized shotgun proteomic method, to provide the most reliable and optimized “gold standard” to the field. (Nature Method, 2009; JASMS, 2009; JPR, 2013).

●  Developed and optimized the proteomics method for ubiquitination to discovered a new role for p97 complex with Npl4-Ufd1as its cofactor in reducing antiviral innate immune responses by facilitating proteasomal degradation of RIG-I. Our study uncovered a previously unrecognized role for the p97 complex in protein ubiquitination and revealed the p97complex as a potential drug target in antiviral therapy. (EMBOJ, 2015).

●  Developed and optimized the crosslink mass spectrometry technology, identified the 1.3 mgadaltgons yeast spliceosome protein complex, and significantly facilitate the structure confirmation of yeast spliceosome at near-atomic-resolution of 3.6-angstrom resolution. (Science, 2015, Science, 2016).

●  Developed software for glycol-peptide data analysis (Nature Communications, 2017).

●  Developed the reference-guided targeted mass spectrometry absolute quantitative method for studying the phosphorylation patterns in protein complex, to reveal the dynamic mechanism of T-cell Receptor in signaling response toward various antigen stimulation. (Submitting to Nature, 2017).

●  Developing a patented micro-fluidic system for single-cell proteomics analysis. (Anal Chem, under review, 2017).

●  Developed integration tools for multi-omics on clinical research and application. 

 

Research Interests

1. Single cell proteomics technology development and the application in translational biomedical research. 

Single cell research rapidly emerges because it provides understanding of the role of cellular diversity in development, health and disease. Benefiting from the next generation sequencing technology, genomic characteristic of single cell is well studied compared to single cell proteome. Although the fast development of mass spectrometry-based shotgun proteomics technology has reached the milestone of identifying more than 13,000 human and 10,000 mouse proteins, it hits a big bottleneck when the protein amounts are limited, especially when it goes to the single cell level.

Our group has been working on a systematics technology development on single cell proteomics and developed a nanoliter-scale oil-air-droplet (OAD) chip by combining droplet-based microfluidics and conventional shot-gun proteomic analysis techniques to achieve multi-step complex sample pretreatment and injection for single cell proteomic analysis. We are focusing on improvement of overall performance of the technology, particularly on the sensitivity issue. Major goal is to make this single cell proteomics technology effective and robust enough to be widely used not only in research laboratory, but also in clinical applications, such as laser-cutting tissue biopsy confirmation at molecular level and embryology researches.  .

2. Absolute quantitative proteomics technology pipeline.

Characterization of protein expression level in different conditions with samples of stable isotope labeling has been studied extensively and become the major approach currently. It is yet an indirect relative measurement which cannot completely unveil the protein changes in the accurate quantity sense. In the past two years, our group has been developing an absolute quantitative method to study tyrosine phosphorylation of T cell receptor (TCR) protein complex. With integration of “synthetic peptides and targeted MS”, we map out the dynamic trajectories of tyrosine phosphorylation of TCR without labeling. The developed absolute quantitation pipeline will be continue applied onto different T cell related projects such as monitoring the T cell response pattern through active immunization, together with the underline mechanism of neoantigen-based cancer vaccines and its clinical efficacy will be studies.  .

3. Multiomics technology for precision medicine study.

Our group is also working on biomarker discovery using multiomics approach. Starts with important clinical problems, through scientifically design of large-scale disease cohort, we integrate cutting-edge high-throughput multiomics technologies to obtain high quality individual molecular information followed by deep learning bioinformatics analysis. After biological and larger population validation, precision biomarkers for diagnosis, prognosis and therapeutics, as well as diseases mechanism would be discovered.

 

Other Expertise

●  Proficient in all different kinds of mass spectrometry analyzers, various ionization techniques, as well as different separation techniques coupling in mass spectrometry.

●  Excellent skills to integrate multi-disciplinary experts, including biologists, clinicians and boinformaticians to carry out large-scale collaboration projects.

 

Publications

1. Li, Z. Y., Huang, M., Wang, X. K., Zhu, Y., Li, J. S.,Wong, C. C. L. *, Fang, Q., Nanoliter-Scale Oil-Air-Droplet Chip-Based Single Cell Proteomic Analysis. Anal Chem, 2018. DOI: 10.1021/acs.analchem.8b00661.

2. Liu, M.Q., Zeng, W.F., Fang, P., Cao, W.Q., Liu, C., Yan, G.Q., Zhang, Y., Peng, C., Wu, J.Q., Zhang, X.J., Tu, H.J., Chi, H., Sun, R.X., Cao, Y., Dong, M.Q., Jiang, B.Y., Huang, J.M., Shen, H.L., Wong, C. C. L.*, He, S.M. and Yang, P.Y. , pGlyco 2.0 enables precision N-glycoproteomics with comprehensive quality control and one-step mass spectrometry for intact glycopeptide identification, Nature Communications, 2017, 8, 438.

3. Tao, Z., Meng, X., Han, Y. Q., Xue, M. M., Wu, S., Wu, P., Yuan, Y., Zhu, Q., Zhang, T. J., Wong, C. C. L. *,Therapeutic Mechanistic Studies of ShuFengJieDu Capsule in an Acute Lung Injury Animal Model Using Quantitative Proteomics Technology. J Proteome Res, 2017, 16, 4009-4019.

4. Hao, Q., Jiao, S., Shi, Z., Li, C., Meng, X., Wang, W., Song, X., Jiang, Z., Zhao, Y., Wong, C. C. L.* and Zhou, Z., A non-canonical role of the p97 complex in RIG-I antiviral signaling, EMBO Journal, 2015, 34(23), 2903-2920.

5. Wong, C. C. L., Cociorva, D., Miller, C. A., Schmidt, A., Monell, C., Aebersold, R., and Yates 3rd, J. R., Proteomics of Pyrococcus Furiosus (PFU): Identification of Extracted Proteins by Three Independent Methods, J Proteome Res., 2013, 12(2), 763-70.