LEMING SHI, Ph.D.

(Data Mining, Bioinformatics, Chemoinformatics, Biochips, and Drug Discovery)

Home:	Office:
14825 Chambery Drive	Center for Toxicoinformatics
Little Rock, AR 72211	National Center for Toxicological Research, US FDA
U.S.A.	3900 NCTR Rd., HFT-020
+1-501-227-8590(H)	Jefferson, AR 72079, USA
+1-501-227-8590(Fax)	+1-870-543-7387(O)
lmshi@helix.nih.gov	+1-870-543-7662(Fax)
lemingshi@yahoo.com	Leming.Shi@fda.hhs.gov
www.gene-chips.com	www.fda.gov/nctr/

OBJECTIVES

To meet the challenges of information explosion in genomics, proteomics, metabonomics, combinatorial chemistry, high-throughput screening, and biochips by using my extensive expertise in data mining, chemoinformatics, bioinformatics, computational chemistry, and chemometrics for the discovery, development, and regulation of better medicine and healthcare for human beings.

EDUCATION

Ph.D. in Computational Chemistry 9/1988-7/1991

Laboratory of Computational Chemistry, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China. Thesis: Chemometrics-assisted resolution of analytical spectra and studies of structure-activity relationships of pesticides and pharmaceuticals. Supervisor: Prof. Zhihong Xu

M.Sc. in Computational Chemistry and Chemometrics 9/1985-7/1988

Department of Modern Chemistry, University of Science and Technology of China, Hefei, China. Thesis: The design of an expert system for planning organic synthetic pathways and applications of chemometrics in chemistry. Supervisor: Prof. Maosen Zhang

B.Sc. in Analytical Chemistry 9/1981-7/1985

Department of Chemistry and Chemical Engineering, Hunan University, Changsha, China. Thesis: Synthesis of a novel chromogenic reagent, 6-Br-BTAQS, and its applications in analytical chemistry. Supervisor: Prof. Guifa Yang

EMPLOYMENT AND MAIN RESPONSIBILITIES

Computational Chemist (Principal Investigator in Biochemoinformatics) 4/2003-Present

National Center for Toxicological Research, FDA, Jefferson, Arkansas. Projects: Quality control and quality assurance of microarrays; Data mining in the areas of genomics, proteomics, and metabonomics as applied to toxicology and drug discovery/development; Systems toxicology.

Co-founder, Director of Informatics 5/2001-4/2003

Chipscreen Biosciences, Ltd., Shenzhen, China. Leading the informatics department to apply state-of-the-art methodologies of computer-aided drug design (CADD) to rationally design novel small molecule drug candidates for treating type 2 diabetes, cancer, osteoporosis, and menopause syndrome; Leading the efforts in designing and implementing an integrated biochemoinformatics software system (TASS) for the efficient storage, management, integration, mining, visualization, and interpretation of various kinds of data (genomics, combinatorial chemistry, HTS, and gene expression profiling) being generated in the Company’s innovative, chemogenomics-based drug discovery programs; Responsible for and successful in grant applications to various funding agencies to support on-going R&D projects in the areas of bioinformatics and chemoinformatics; Responsible for directing several Ph.D. candidates from the Chinese Academy of Sciences.

Senior Scientist 7/2000-5/2001

BASF Corp., Princeton, New Jersey. Projects: Data mining for massive gene expression data from DNA microarrays; Design of combinatorial libraries; Data mining for high-throughput screening; Molecular modeling, quantitative structure-activity relationships, pharmacophore identification and 3D database searching, and molecular diversity analysis; Computer-aided molecular design; Supervising and training of organic and computational chemists within the Company to apply cutting-edge methodologies for molecular design and data mining.

Senior Research Chemist 8/1999-6/2000

American Cyanamid Company (a subsidiary of American Home Products Corp., now Wyeth), Princeton, New Jersey. Projects: Data mining for massive gene expression data from DNA microarrays; Design of combinatorial libraries; Data mining for high-throughput screening; Molecular modeling, quantitative structure-activity relationships, pharmacophore identification and 3D database searching, and molecular diversity analysis; Computer-aided molecular design. Supervising and training of organic and computational chemists within the Company to apply cutting-edge methodologies for molecular design and data mining.

Senior Computational Chemist 12/1997-8/1999

R.O.W. Sciences, Inc. (now Northrop Grumman Information Technology), National Center for Toxicological Research, FDA, Jefferson, Arkansas. Projects: Data mining, classification and clustering, QSAR, pharmacophore identification, and molecular diversity analysis for priority setting of tens of thousands of compounds that may bind to the estrogen receptor (ER); Proposed and developed an integrated, "4-Phases" computational approach to priority setting in screening large libraries of compounds; Structure-carcinogenicity/mutagenicity relationships of NTP-tested compounds; Development of a highly rated Web site on gene-chips and DNA microarrays (http://www.gene-chips.com), which was reviewed favorably and recommended several times by Science magazine (1999 August 6; 285(5429): 799, etc.) and cited by journals like Nature. The high-profile projects at the FDA helped to attract attention from management teams of both FDA and EPA, and resulted in a substantial grant for supporting the research group.

Visiting Fellow 9/1995-12/1997

Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, Maryland, with Dr. John N. Weinstein. Projects: Data mining and visualization of large databases (structures, biological activities, and targets or modulators) generated by the NCI anticancer drug discovery program; Identification of CNS- and p53-mutation selective anticancer agents; Pharmacophore identification and 3D database searching; Molecular modeling of DNA-topoisomerase I ternary cleavable complexes with camptothecins.

Research Associate 9/1994-9/1995

Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, with Prof. Gilles Klopman. Projects: 2D substructural QSAR studies of multidrug resistance reversal agents in cancer; Prediction of carcinogenicity, mutagenicity, and acute toxicity of several sets of diverse compounds; Metabolism study using the META program.

Assistant and Associate Research Professor 7/1991-8/1994

Laboratory of Computational Chemistry, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China. Projects: Several award-winning projects on the application of chemometrics and artificial neural networks in molecular design and data mining in analytical chemistry; Developed (in C) a comprehensive chemometrics software package.

Assistant and Vice President 7/1992-8/1994

Beijing BioMat Biotechnology and Material Sciences Engineering Research & Development Center, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China. Responsible for the overall business development of the Center and negotiations with industrial partners on cooperative projects and technology transfer deals.

RESEARCH INTERESTS

1. Systems biology and toxicology

2. Data mining for DNA microarray gene expression profiling, SELDI-TOF protein profiling, and NMR metabolic profiling

3. Knowledge discovery, data mining, and visualization in chemistry and biology

4. Bioinformatics, chemoinformatics, toxicoinformatics, and chemometrics

5. Identification of disease-related genes

6. Computer-aided drug design and toxicity prediction

7. Structure-based drug design

8. Molecular diversity analysis and combinatorial library design

9. Pharmacophore identification and 3D database searching

10. Databases, expert systems, machine learning, and artificial intelligence

11. Chemical and biological information exchange on the WWW

PROFESSIONAL EXPERTISE

1. Extensive (18 years) experience in programming, algorithm development, and application of state-of-the-art technologies of statistics, expert systems, machine learning, and artificial intelligence in solving challenging problems in chemistry and biology

2. Formal training and extensive programming experience in Statistics, Data Structures, Software Engineering, Databases, Artificial Intelligence, Expert Systems, Pattern Recognition, Fuzzy Set Theory, Neural Networks, Genetic Algorithms, Chemical Structure Processing, Molecular Diversity Analysis, etc.

3. Broad knowledge on chemistry, biology, pharmacology, and toxicology

4. Understanding of human diseases, such as cancer, endocrine disruption, and diabetes

5. Familiarity with the drug development process and FDA drug reviewing procedures

6. Extensive laboratory experience in UV/Vis, FTIR, FTNIR, GC, HPLC, AAS, etc.

7. Strong publication records (80+ papers and book chapters)

8. Creative, self-motivated, diligent, team-worker, and a quick learner

COMPUTER SKILLS

1. Platforms: PC, Macintosh, DEC Vax, DEC Alpha, IBM and SGI workstations

2. Operating Systems: DOS, Windows/NT, VMS, and Unix/Linux

3. Languages: Basic, Fortran, Pascal, LISP, Prolog, C, C++, SAS/JMP, S-Plus, Matlab, HTML, Visual Basic, Tcl/Tk, Perl, and CGI

4. Molecular Modeling and bioinformatics: Sybyl, Cerius², InsightII, CODESSA/AMPAC, APEX-3D, MOE, MOPAC, Gaussian, Quanta/CHARMm; Protein and DNA sequence analysis packages (e.g. GCG)

5. Databases and Diversity Analysis: Oracle, Access, ISIS/Base/Host/Chemscape, Unity, Catalyst, Chem-X, Concord, Corina, NCI drug information system, Cambridge structural database, Brookhaven protein data bank, Protein and nucleic acid sequence databases, DiverseSolutions, Legion/Selector

6. Genetic Linkage Analysis: SOLAR, SLINK, LINKAGE and FASTLINK.

RECENT TRAINING/CONFERENCES/SEMINARS

1. Chemistry and Biology: Partners in Decoding the Genome, Bethesda, Maryland, March 15-16, 2004.

2. The Second Committee Meeting of IUPAC Task Force on Biochips and Nanotechnology, London, U.K., December 2-4, 2002. Invited and funded by the IUPAC.

3. International Forum on Biochip Technologies, Beijing, China, November 9-13, 2002. Invited and funded by the organizing committee.

4. The First Committee Meeting of IUPAC Task Force on Biochips and Nanotechnology, Palm Springs, California, January 28, 2002. Invited and funded by the IUPAC.

5. LabAutomation2002, Palm Springs, California, January 28-30, 2002.

6. Gene Expression and Proteomics in Environmental Health Research, National Institutes of Health, Bethesda, Maryland, December 3-4, 2001.

7. 221st American Chemical Society National Meeting, San Diego, CA, April 1- 5, 2001.

8. HTS Technologies, Stuttgart, Germany, December 4-6, 2000. (IBC)

9. International Forum on Biochip Technologies, Beijing, China, October 11-14, 2000. Invited and funded by the organizing committee.

10. Bioinformatics Symposium, Princeton University, January 19, 2000.

11. Innovative Computational Applications: The Interface of Library Design, Bioinformatics, Structure Based Drug Design and Virtual Screening, San Francisco, California, October 25-27, 1999. (IIR)

12. 1999 Keystone Symposia on Endocrine Disruptors (B5), Tahoe City, California, January 31 - February 5, 1999.

13. Drug Discovery Technology'98: Breaking the Bottleneck: Innovation and Speed in Drug Discovery, Boston, Massachusetts, August 10-13, 1998. (IBC)

14. DNA Microarray: Current Technology and Future Applications Workshop, Bethesda, Maryland, July 14-15, 1998. (FDA)

15. Short course on clustering during the Joint Annual Meeting of the Classification Society of North America and the Psychometric Society, Urbana, Illinois, June 17-21, 1998.

16. 215th American Chemical Society National Meeting, Dallas, Texas, March 29 - April 2, 1998.

17. American Chemical Society Short Course on Molecular Biology and Recombinant DNA Technology, Dallas, Texas, March 27-28, 1998.

18. Principles of Toxicology (3 credit hours course), NIH, 1997.

19. From Molecules to the Market: FDA Drug Reviewing Procedures (3 credit hours course), FDA/NIH, 1997.

EDITORIAL ADVISORY BOARD

1. Computers and Applied Chemistry (China), since 2000

2. Expert Review of Molecular Diagnostics (UK), since 2001

JOURNAL REFEREE

1. Journal of Chemical Information and Computer Science

2. Journal of Medicinal Chemistry

3. Molecular Pharmacology

4. Bioinformatics

5. Briefings in Bioinformatics

6. Trends in Biotechnology

7. BioTechniques

8. Computers and Applied Chemistry

9. Expert Review of Molecular Diagnostics

10. Journal of VLSI Signal Processing

11. Pattern Analysis & Applications

12. Journal of Biopharmaceutical Statistics

13. Journal of Biomedical Nanotechnology

14. Frontiers in Bioscience

15. Journal of Computational Chemistry

16. Machine Learning

17. Biotechnology and Bioengineering

GRANT REVIEWER

1. The Department of Energy, USA

2. The Department of Agriculture, USA

3. The National Institutes of Health (NIH), USA

4. The Food and Drug Administration (FDA), USA

5. The Environmental Protection Agency (EPA), USA

6. American Society for Microbiology, USA

HONORS AND OTHER SPECIAL SCIENTIFIC RECOGNITION

1. Member of the USEPA Review Panel on Computational Toxicology & Endocrine Disruptors: Use of Systems Biology in Hazard Identification & Risk Assessment, Washington, DC, May 11, 2004.

2. Member of the USEPA Review Panel on the Development of High-Throughput Screening Approaches for the Endocrine Disruptor Program, Washington, DC, May, 2003. Invited.

3. Interviewed and reported by Science magazine several times for work on microarrays, bioinformatics, and chemoinformatics, see e.g. http://www.sciencemag.org/content/vol285/issue5429/netwatch.shtml; http://www.sciencemag.org/feature/e-market/benchtop/dnamicro.shl; http://www.sciencemag.org/feature/e-market/benchtop/dnachips.shl

4. Interviewed and reported by BioInform magazine on “Solutions: China’s Chipscreen builds an integrated bio-chemoinformatics system” (http://www.bioinform.com/), BioInform, 7(12), p.3, March 24, 2003

5. Member of the IUPAC (International Union of Pure and Applied Chemistry) Task Force on Biochips and Microtechnology, since 2001

6. First Place Award Winner from Shenzhen Municipal Government for Honoring Oversea Chinese Returnees with Extraordinary Contribution to Shenzhen’s High-Tech Industry, 2002. (Cash award of 120,000 RMB, approx. 15,000 USD)

7. Principal Investigator of three bioinformatics grants awarded by China’s Department of Science and Technology, 2002: a) Informatics system for microarray gene expression; b) Prediction of structure and function of proteins; and c) Grid computing for drug discovery and development

8.