Biologist

Lili Huang

PROFILE

Technically sophisticated, versatile, and performance-driven professional with proven expertise in biochemistry, molecular biology, and macromolecular structural biology, with strong background in working nucleic acids and proteins, including preparation, purification, assay development and interactions analysis with potential drug targets; interested in pursuing career in a challenging, stimulating, and fast-paced collaborative team environment within various fields.

Demonstrate ability of multitasking and producing results in a competitive environment; Professional skills in writing scientific papers and oral presentation; Strong record of academic publications.

KEY SKILLS

• Extensive experience with molecular biology strategies, e.g. PCR, primer design, DNA/protein sequence analysis, SDS-PAG, cloning, mutagenesis, enzymatic reactions, gene construction, cell culture (E.coli., and insect cell).

• Extensive knowledge and hands-on experiences with protein expression (E. coli and Baculovirus-insect cell system), purification (GE healthcare AKTA FPLC system, Unicorn software and a variety of chromatographic system), refolding, and characterization.

• Expertise with nucleic acids in vitro synthesis/transcription and purification by electrophoresis (PAAG) and chromatography (size exclusive, affinity, hydrophobic and ion exchange column).

• Full knowledge and experience in chromatography column packing (manual prepared column experience) and understanding of scale up principals.

• Extensive experience in bioanalytical methods, including Electrophoresis (PAGE), Isothermal Titration Calorimetry (ITC), Fluorometry, UV-Vis Spectroscopy, X-ray diffraction, Analytical chromatography, Foot-printing, Equilibrium dialysis, Isotopic labeling techniques, FPLC, TLC, autoDOCK, binding assay development etc.

• Excellent knowledge of protein/RNA/DNA crystallization (manual and automated crystallization) and optimization, x-ray data collection (home and synchrotron) and process (HKL2000), three dimensional structure determination (MR, MAD, SAD etc), interactions analysis of macromolecule and potential drug target with close attention to details.

• Familiar with Windows/Unix/Linux system, MS Office, Illustrator, crystallographic softwares (CCP4, Phenix, Sharp, HKL, Pymol, Coot), PDB data submission.

EDUCATION

Ph.D. Structural Biology

Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, China 2001-2007

B. S. Chemistry

Henan University, China 1997-2001

PUBLICATIONS AND PATENT

1. Huang L, Ishibe-Murakami S, Patel DJ, Serganov A. Long-range pseudoknot interactions dictate the regulatory response in the tetrahydrofolate riboswitch. Proc Natl Acad Sci U S A, (2011), 108(36), 14801-6

2. Huang L*, Serganov A*, Patel DJ. (*These authors contribute equally to this work) Structural insights into ligand recognition by a sensing domain of the cooperative glycine riboswitch. Mol Cell, (2010), 40(5), 774-86.

3. Huang L, Serganov A, Patel DJ. Structure of glycine-sensing riboswitch: insights into ligand recognition and cooperativity. 15th Annual meeting of the RNA society, June, 2010, Seattle.

4. Serganov A*, Huang L*, Patel DJ. (*These authors contribute equally to this work) Coenzyme recognition and gene regulation by a FMN riboswitch. Nature, (2009), 458(7235), 233-7.

5. Serganov A*, Huang L*, Patel DJ. (*These authors contribute equally to this work) Structural insights into amino acid binding and gene control by a lysine riboswitch. Nature. (2008), 455(7217), 1263-7.

6. Lili Huang, Dawei Ma, Zongxiang Xia, Molecular Modeling of Interactions of the Benzolactam-V8 Modulators with the Cys2 Domain of Protein kinase C . Chinese Journal of Chemistry (2007), 25(10), 1434-1438

7. Lili Huang, Xuemei Zhao, Chaoqun Huang, Long Yu, Zongxiang Xia, Structure of recombinant human Cyclophilin J, a novel member of the cyclophilin family, Acta Cryst. (2005) D61, 316-321

8. Lili Huang, Zongxiang Xia, Crystal structure of recombinant human cyclophilin J and its complex IUCr, 2005, Fluorence, Italy

9. Lili Huang, Zongxiang Xia, Crystallization of human cyclophilin J, ICCBM 10, 2004 (10th International conference on the crystallization of biological macromolecules), Beijing, China

10. Bingzhi Chen, Chaojie Wang, Jinyong Song, Lili Huang, Xinqi Sun, Jin Zhao, Improved method for the preparation of tert-butyl hydroperoxide and tert-butyl peroxide. Huaxue Shiji (2000), 22(6), 368.

11. Pub No. WO/2009/120347, Patel DJ, Serganov A, Huang L, Modulators of RNA riboswitches.

RESEARCH EXPERIENCE

Research Associate (2010-2011); Research Fellow (2007-2010)

Principle investigator: Dinshaw J. Patel; Memorial Sloan-Kettering Cancer Center, New York, NY

• Research: Conducted comprehensive research on riboswitches, a RNA-based gene regulatory element. Their role in regulating transcription or translation in bacteria makes them enticing targets for the development of novel antibiotics aimed at stopping bacterial pathogens from flourishing inside the people they infect.

1) Structural research on a flavin mononucleotide (FMN) riboswitch, complemented by fluorometric binding assay and footprinting, reveal an inherent plastic FMN-binding pocket, showing that FMN riboswitch is an attractive target for structure-based design of FMN-like antimicrobial compounds. Results also explain the effects of spontaneous and antibiotic-induced deregulatory mutations and provide molecular insights into FMN-based control of gene expression in normal and riboflavin-overproducing bacterial strains.

2) Effectively studies on lysine riboswitch provide insights into amino acid binding and explained the downstream riboswitch-dependent gene regulatory mechanism, thereby contributing to continuing efforts at exploration of the pharmaceutical and biotechnological potential of riboswitches. Further biochemical studies on lysine analogues, including antibiotics, make an effort to understand the ligand-binding capabilities and the nature of antibiotic resistance.

3) Structural and biochemical researches of glycine riboswitch showed that glycine recognition is facilitated by Mg2+ cations and governed by specific interactions and shape complementarity with the pocket. Analysis of riboswitch interactions, ITC experiments and footprinting assays indicates specific interdomain interactions, potentially contributing to the specific cooperative response, which is a rare case in RNA world.

4) Studies on Tetrahydrofolate (THF) riboswitch revealed long-range pseudoknot interactions which dictate the regulatory response in the THF riboswitch, and demonstrate that THF riboswitch uses only limited determinants for ligand recognition. Given that modern antibiotics target folate metabolism, results provide insights on mechanistic aspects of riboswitch function and may help in manipulating THF levels in pathogenic bacteria.

• Leadership: Supervised technicians and undergraduate/high school students doing projects.

• High Productivity: Produce high quality results continuously, Nature (2008), Nature (2009), Mol Cell (2010), Proc Natl Acad Sci (2011), Patent Pub No. WO/2009/120347

• Top-rated Performance: Earned outstanding reviews from my supervisor, with special recognition for teamwork, attention to details.

Doctor of Philosophy Studies (2001-2007)

• Effectively conducted investigation on human cyclophilin J, a new member of ubiquitous peptidyl-prolyl cis-trans isomerase family, and its interactions with the immunosuppressive drug cyclosporin A (CsA).

• Working collaboratively with organic chemistry group, molecular modeling and stimulation of interactions between four 7- or 8-substituted benzolactam-V8 molecules and the cys2 activator-binding domain of protein kinase C (PKC ). Results predicted a potent activator of PKC .

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