Scientist, Chemist

CHENG-CHI CHUANG

SUMMARY

• Biophysical/Bioanalytical Chemist with 10 years of experience in the drug discovery industry

• Expertise in in vitro pharmacology, protein-ligand in vitro binding assays, High Throughput Screen, and chemi-physical properties characterization of proteins and small molecules

• Expertise in supporting Target Validation, HTS hit validation, Lead ID and Ligand Optimization programs spanning from Oncology, Inflammation, Anti-infective, Atherosclerosis, Diabetics and Anti-viral diseases

• Familiar with structure-based drug design, combinational library design, DMPK, bioinformatics, protein purification and antibody hybridoma technology

• Technical specialties: In vitro binding assay (ELISA, ITC, SPR, DSC, TdCD and thermal shift assay), Mass Spectrometry (ESI-TOF-MS, ESI-Ion-Trap-MS and MALDI), analytical instrumentation (LC-MS, GC-MS, FTIR and NMR), fluorescence-based detection techniques (LIF and Stopped-Flow), laser spectroscopy (NIR/IR/VIS/UV), lab automation and software development

• Strong instrumental, analytical, organizational, and managerial skills

EDUCATION

Harvard University, Department of Chemistry and Chemical Biology, Cambridge, MA

Postdoctoral Fellow/Research Associate (1995-2000)

University of Pennsylvania, Philadelphia,PA

Ph.D., Physical Chemistry (July 1995)

National Sun Yat-Sen University, Kaohsiung, Taiwan

B.S., Chemistry (May 1986)

RESEARCH EXPERIENCE

MERCK RESEARCH LABORATORIES, Cambridge, MA

Principal Scientist, Protein Science Department (11/2009 – 12/2010)

* Supported Target Validation, Hit Validation, Lead ID and Lead Optimization programs by in vitro thermal shift assay (targets across different therapeutic areas including oncology, inflammation, anti-infective, atherosclerosis, diabetics, and anti-viral diseases)

* Supported protein QC using Ion-Trap-ESI and TOF-ESI mass spectrometry, DLS, DSC, CD, TdCD and thermal shift assay

SCHERING-PLOUGH RESEARCH INSTITUTE, Cambridge, MA

Principal Scientist, Protein Science Department (09/2007 – 11/2009)

* Supported hit validation, hit-to-lead and lead optimization programs by thermal shift assay (investigated an average of 26 targets & 6000+ compounds/per year)

* Developed fully automated 384-WP Temperature Dependent Fluorescence (TdF) affinity-based in vitro screen platform (throughput: Kd determination for 380 compounds in one hour)

* Supported protein QC using Ion-Trap-ESI and TOF-ESI mass spectrometry, DLS, DSC, CD, TdCD and thermal shift assay

Principal Scientist, Technology Development (02/2005 – 09/2007)

* Supported hit-to-lead and ligand optimization programs using co-developed affinity selection-mass spectrometry-based Automated Ligand Identification System (ALIS) technology

* Worked with program managers to design ALIS-based experiments to investigate the protein-ligand binding affinity, lgand binding site classification, ligand binding thermodynamics, and ligand binding kinetics

* Evaluated performance of NanoSpray Mass Spectrometry and its potential to enhance the capability and sensitivity for the existing ALIS platform (through external collaboration with Agilent)

NEOGENESIS PHARMACEUTICALS, INC. Cambridge, MA

Start-up drug-discovery company focused on using its proprietary technologies to identify and develop a Portfolio of small molecule-based drugs.

Senior Research Scientist, ALIS department (2001-2005)

* Co-developed NeoGenesis’s core drug discovery platform, the affinity selection-mass spectrometry-based Automated Ligand Identification System (ALIS)

* Installed and validated ten LC-MS work stations far ahead of schedule which enhanced the HTS capability/capacity for Neogenesis

* Co-developed methods in protein-ligand binding affinity measurement (Kd), binding site classification, and binding affinity ranking in compound mixtures via ALIS technology, which lead to patent and peer-reviewed journal publications

* Supported hit validation, hit-to-lead and ligand optimization programs by ALIS technology

* Supervised/trained junior scientists and tracked their research project’s progress including hardware operation/maintenance, data analysis, and result review/presentation.

HARVARD UNIVERSITY, DEPARTMENT OF CHEMISTRY, Cambridge, MA

Postdoctoral Research Fellow/Research Associate (July 1995-December 2000)

* Extensive experience in detecting trace gaseous species using FTIR, Ti-Sapphire pumped ring-dye laser, and intracavity infrared laser induced fluorescence techniques.

* Designed and operated spectrometer in detecting IR, NIR and VIS/VIS fluorescence using Ge, PbS, InSb , PMT and CCD array detectors.

* Participated in Biochemistry/Biophysical Chemistry seminars/workshops to gain knowledge in protein-ligand interaction, protein-protein interaction, drug discovery, and proteomics research. Familiar with techniques of ESI, MALDI, CE, Single Molecule Spectroscopy, FRET (fluorescence resonance energy transfer), FCS (fluorescence correlation spectroscopy) and FILM (fluorescence life-time imaging microscopy)

UNIVERSITY OF PENNSYLVANIA, DEPARTMENT OF CHEMISTRY, Philadelphia, PA

Research & Teaching Assistant (1989-1995)

* Developed instrumentation in formation and detection of gaseous reactive radicals using laser photolysis, laser induced fluorescence and molecular beam techniques.

* Extensive experience in interfacing laboratory instruments; expert in Excimer, Nd:YAG, and dye lasers, optics and high vacuum technology.

* Extensive experience in TOF-MS, QMS, UV/VIS, GC/MS, NMR and HPLC

AWARDS

Postdoctoral research associate supported by National Science Foundation (1995 – 1997)

SELECTED PUBLICATIONS(2004-2011)

1. D. Allen Annis, Naim Nazef, Cheng-Chi Chuang, Margaret Porter Scott and Huw M. Nash, “ A General Technique to Rank Protein-Ligand Binding Affinities and Determine Allosteric vs. Direct Binding Site Competition in Compound Mixtures”, J. Am. Chem. Soc., 126, 15495 (2004)

2. Annis, D.A.; Chuang, C.-C; Nazef, N. ALIS: An Affinity Selection-Mass Spectrometry System for the Discovery and Characterization of Protein-Ligand Interactions in “ Mass Spectrometry in Medicinal Chemistry: Applications in Drug Discovery”, vol. 36, pp. 121-156, (2007), Wiley-VCH Press

3. Shipps, Gerald Ma, Yao Lahue, Brian Seghezzi, Wolfgang Herbst, Ronald Chuang, Cheng-Chi Annis, D. Allen Kirtley, Matthew. Compounds for Inhibiting KSP Kinesin Activity, Patent. United States of America, USA : World Intellectual Property Organization, 2008. Number : US 2008/153701 A1. Owner : Schering Plough. Registration : 24.05.2007. Accepted : 18.12.2008.

4. D. Allen Annis, Cliff C. Cheng, Cheng-Chi Chuang, John D. McCarter, Huw M. Nash, Naim Nazef, Todd Rowe, Robert J. M. Kurzeja and Gerald W. Shipps, “ Inhibitors of the Lipid Phoshatase SHIP2 Discovered by HighThroughput Affinity Selection-Mass Spectrometry Screening of Combinational Libraries”,Combinational Chemistry & High Throughput Screening, 12, 760-771 (2009)

5. Payal R. Sheth, Gerald W. Shipps, Jr., Wolfgang Seghezzi, Catherine K. Smith, Cheng-Chi Chuang, David Sanden, Andrea D. Basso, Lev Vilenchik, Kimberly Gray, D. Allen Annis, Elliott Nickbarg, Yao Ma, Brian Lahue, Ronald Herbst, and Hung V. Le, “Novel Benzimidazole Inhibitors Bind to a Unique Site in the Kinesin Spindle Protein Motor Domain”, Biochemistry, 49, 8350–8358 (2010)

6. Yongqi Deng, Gerald W. Shipps Jr., Alan Cooper, William T. Windsor, Jessie M. English, D. Allen Annis, Donna Carr, Yang Nang, Tong Wang, Hugh Y Zhu, Cheng-Chi Chuang, Priya Dayananth, Alan W. Hruza, Li Xiao, Ahmed Samatar, “Discovery of Novel, Dual Mechanism ERK Inhibitors By Affinity Selection Screening of An Inactive Kinase State”, (submitted to J. Med. Chem.)

7. Hong Lan, Cliff Cheng, Timothy Kowalski, Ling Pang, Lixin Shan, Cheng-Chi Chuang, James Jackson, Alberto Rojas-Triana, Loretta Bober, Li Liu, Johannes Voigt, Peter Orth, Xianshu Yang, Gerald Shipps, and Joseph Hedrick,” Small Molecule Dual FABP4/5 Inhibitors Ameliorate Dyslipidemia in Mice with Diet-Induced Obesity” , J. Lipid. Res. (2011)

8. “A Journey in Drug Discovery with the Automated Ligand Identification System (ALIS): From High Throughput Screening to Hit-to-Lead Optimization”, invited talk, International Taiwan Biobank Conference, Taipei, Taiwan, August 13-15 (2007)

REFERENCES Available upon request

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