生物医用材料系列讲座

         

 ―――2007年12月13日（星期四）

                

       

上午9:30－11:00

报告人：美国Intradigm公司高级研究员丁中立博士

1．            Protein Formulation and Delivery

2．            Control of Protein Activities by Conjugation of Stimuli-responsive Polymers to Proteins

主持人：陈捷

地点：嘉定校区2教211

 

欢迎广大师生踊跃参加。

联系人：郝  健（Tel：66133380）

陈  捷（Tel：69982836）

 

 

 

 

 

 

Zhongli Ding, PhD

 

408-739-2728, zlding@sbcglobal.net

 

丁中立博士简介：获美国华盛顿大学生物工程系博士；主要从事蛋白类药物的研究与应用开发。曾任美国ALZA公司研究员、美国J&J公司药物研发部研究员；现任美国Intradigm公司研究员高级研究员；曾在国际学术刊物及国际会议上发表论文20余篇，获美国专利2项。作为第一作者，近期在Nature杂志上发表论文1篇。

Summary

An experienced PhD with knowledge and skills in developing and characterizing protein drug formulations and delivery systems

 

Work Experience

October 2007 – present: Principle Scientist, Intradigm

January 2007 – October, 2007:  Senior Staff Engineer, Centocor

·         Led many complex studies in developing a novel technology of delivering high concentrations of biopharmaceuticals..

·         Studied alternative routes of delivery biopharmaceuticals

·         Developed a novel microencapsulation technology for sustained drug delivery

·         Participated in technology transfer to CMO.

·         Participated in GXP trainings.

 

October 2000 – December 2007: Senior Staff Engineer, ALZA Corp

·         Formulated protein drugs

o        Developed stable protein formulations by optimizing excipient compositions

o        Developed spray-drying process to generate stable protein microparticles and characterized the products.

o        Characterized formulated proteins with HPLC, DSC, ITC, and spectroscopy.

·         Worked in teams to develop parenteral delivery systems for protein drugs

o        Developed biodegradable polymer vehicles by engineering polymer compositions. Thermal analysis, rehology analysis, HPLC, spectroscopy were employed to characterize the research systems.

·         Engaged in PK studies using rat models.

·         Studied in vitro release methods to simulate in vivo release.

·         Applied “Design of Experiment” principle to design studies and analyzed research results using statistic software.

·         Initiated and led several research projects. Supervised assistants.  Frequently advised junior researchers.

·         Familiar with GLP and GMP. (An annual training is mandatory at ALZA)

 

June 2000 – September 2000: Post Doctoral Fellow, Department of Bioengineering, University of Washington, Seattle, WA

·         Developed a radioactive coating for a cardiovascular implant.

 

September 1995 - June 2000: Ph.D. Research, Department of Bioengineering, University of Washington, Seattle, WA.

·         Designed, constructed and expressed site-directed streptavidin mutants by genetic engineering, bacterial expression, protein refolding, and affinity chromatography.

·         Designed, synthesized, purified and characterized temperature- and pH-sensitive polymers.  In order to obtain a polymer with narrow molecular weight distribution, group transfer living polymerization was employed.  The end groups of the polymers were further derivatized such that site-specific protein-polymer conjugation could be achieved.

·         Conjugated, purified and characterized various polymers to streptavidin mutants at different loci around the biotin-binding site. Developed a complete set of methodologies for synthesis, separation and characterization of the conjugates.

·         Characterized proteins and conjugates using size exclusion chromatography, perfusion chromatography, affinity chromatography, MALDI, IR, NMR, Scanning Probe Microscopy, Dynamic Light Scattering and ELISA.

·         Developed a polymer-streptavidin conjugate that controls the binding of biotin or biotinylated proteins and enables thermal-triggered release of biotin.

 

May 1993 - August 1995: Visiting Scholar, Center for Bioengineering, University of Washington, Seattle, WA.

·         Synthesized temperature-sensitive polymer and prepared polymer-enzyme and antibody conjugates for thermal-stimulated separations.

·         Prepared temperature- and pH-sensitive hydrogels for drug delivery.

 

July 1985 - May 1993: Researcher, Shanghai Applied Radiation Institute, Shanghai University of Science and Technology, Shanghai, China.

Prepared and modified polymeric biomaterials used for drug delivery using high-energy electron beam and g-irradiation from a 60Co source. Following techniques were used to study and characterize the biomaterials: TMA (Thermal Mechanical Analysis), DSC (Differential Scanning Calorimetry ), ESR (Electron Spin Resonance) and SEM (Scanning Electron Microscopy).

 

July 1990 - April 1991: Visiting Scholar, Takasaki Radiation Chemistry Research Establishment, Japan Atomic Energy Research Institute, Takasaki, Gunma, Japan.

Synthesized, characterized and utilized stimuli-sensitive polymers for drug delivery applications.  The acrylic backboned polymers contained various amino acid pendant groups.

 

Education

Ph.D., Molecular Bioengineering, June 2000,

Department of Bioengineering, University of Washington, Seattle, WA 98195.

Dissertation: Control of protein activity by conjugation of stimuli-responsive polymers to proteins.

Advisors: Allan S. Hoffman and Patrick S. Stayton.

 

M.S., Radiation Chemistry, July 1985,

Shanghai University of Science and Technology, Shanghai, China.

Dissertation: Pre-irradiation grafting of hydrophilic monomers on hydrophobic polymers.

 

B.S., Polymer Science, July 1982,

Shanghai University of Science and Technology, Shanghai, China.

Dissertation: Application of immobilized glucose oxidase for determination of blood glucose.

PUBLICATIONS

 

Manuscripts

·         Z. Ding, R. B. Fong, C. J. Long, P. S. Stayton and A. S. Hoffman, Size-dependent control of the binding of biotinylated proteins to streptavidin using a polymer shield, Nature, 411, 59-62, (2001).

·         P. S. Stayton, Z. Ding, A. S. Hoffman, Smart polymer-streptavidin conjugates. Methods Mol Biol., 283, 37-43 (2004).

·         N. Malmstadt, D. E. Hyre, Z. Ding, A. S. Hoffman, P. S. Stayton, Affinity thermoprecipitation and recovery of biotinylated biomolecules via a mutant streptavidin-smart polymer conjugate. Bioconj. Chem., 14, 575-80 (2003).

·         T. Shimoboji, Z. Ding, P. S. Stayton and A. S. Hoffman, Photoswitching of ligand association with a photoresponsive polymer-protein conjugate. Bioconj. Chem., 13, 915-9 (2002).

·         T. Shimoboji, Z. Ding, P. S. Stayton, A. S. Hoffman, Mechanistic investigation of smart polymer-protein conjugates. Bioconj. Chem., 12, 314-9 (2001).

·         S. Anastase-Ravion, Z. Ding, A. Pe1lé, A. S. Hoffman, and D. Letourneur, New antibody purification procedure using a thermally responsive poly(N-isopropylacrylamide)-dextran derivative conjugate, J. of Chromatography, 761, 247-254 (2001)

·         Z. Ding, C. J. Long, Y. Hayashi, E. V. Bulmus, A. S. Hoffman and P. S. Stayton, Temperature control of biotin binding and release with a streptavidin-poly(N-isopropylacrylamide) site-specific conjugate, Bioconj. Chem., 10, 395-400, (1999).

·         R. Fong, Z. Ding, C. J. Long, A. S. Hoffman and P. S. Stayton, Thermoprecipitation of Streptavidin via Oligonucleotide-Mediated Self-Assembly with Poly(N-isopropylacrylamide), Bioconj. Chem., 10, 720 -725, (1999).

·         A. S Hoffman, G. Chen, X. Wu, Z. Ding, J. E. Matsuura, W. R. Gombotz, Stimuli-Responsive Polymers Grafted onto Polyacrylic Acid and Chitosan Backbones as Bioadhesive Carriers for Mucosal Drug Delivery, Frontiers in Biomedical Polymer Applications, 2, 17-29, (1999).

·         E. V. Bulmus, Z. Ding, C. J. Long, P. S. Stayton and A. S. Hoffman, A pH- and Temperature-Sensitive Copolymer-Streptavidin Site-Specific Conjugate for pH-Controlled Binding and Triggered Release of Biotin, Bioconj. Chem., 11, 78-83, (2000).

·         Z. Ding, G. Chen and A. S. Hoffman, Unusual properties of thermally sensitive oligomer-enzyme conjugates of poly(N-isopropylacrylamide)-trypsin, J. Biomed. Mater. Res., 39, 498-505, (1998).

·         Z. Ding, G. Chen and A. S. Hoffman, Synthesis and purification of thermally-sensitive oligomer-enzyme conjugates of poly(N-isopropylacrylamide)-trypsin, Bioconj. Chem. 7, 121-125, (1996).

·         M. Wu, Z. Ding, and Z. Ma, The effect of monomer molecular weight of acrylate on radiation grafting of polyethylene, J. of Radiation Research and Radiation Processing, 13, 146-150, (1995).

·         Z. Ding, M. Yoshida, M. Asano, Z. Ma, H. Omichi and R. Katakai, Thermo-responsive behavior of a methacryloyl-DL-Alanine methyl ester polymer gel prepared by radiation-induced polymerization, Radiat. Phys. Chem., 44, 263-272, (1994).

·         Z. Ding, H. Pu, H. Ye, and Z. Ma, A Thermo-sensitive material prepared by pre-irradiation grafting of NIPAAm onto EVA polymer, J. of Radiation Research and Radiation Processing, 12, 12-17, (1994).

·         H. Pu, Z. Ding and Z. Ma, EVA pre-irradiated NIPAAm and its surface properties J. Shanghai Jiaotong University , 28, 102 - 108, (1994).

·         Z. Ding, M. Yoshida, Z. Ma and M. Kumakura, A Study on The Deswelling Behavior of a Thermal-responsive Hydrogel Prepared by Radiation Polymerization, Radiat. Phys. Chem. 42, 959 - 962, (1993).

·         Z. Ding and M. Wu, Synthesis of Condensed Ethylene Glycol Acrylate, J. of Shanghai University of Science and Technology, 14, 100, (1991).

·         J. Hua, X. Zhang, L. Liu, Z. Ding, B. Shi, Z. Zhang, Z. Xiu, and M. Dai, Measurement of blood glucose content using immobilized glucose oxidase, Chinese Journal of Medical Laboratory Technology, 7, (1984).

 

Abstracts

·         J. M. Berg, T. Shimoboji, T. Inoue, Z. Ding, A. S. Hoffman, F. Zavala, J. B. Castelino, and V. Markovic, A new process combining gas discharge treatment and adsorption of a cationic polymer to enhance immunoassay tests, 21st Annual Meeting of the Society for Biomaterials, San Francisco, CA, (1995).

·         A. S. Hoffman, G. Chen, T. Inoue, Z. Ding and S. Kaang, Stimuli-responsive graft copolymers with dual sensitivities, International Symposium on Biomedical Polymers - Advanced Biomaterials and Biomedical Engineering and Drug Delivery System, Kagoshima University, Japan, April, (1995).

·         Y. Nabeshima, Z. Ding, G. Chen, A. S. Hoffman, H. Taira, K. Kataoka, and T. Tsuruta, Slow release of heparin from a hydrogel made from polyamine chains grafted to a temperature-sensitive polymer backbone, International Symposium on Biomedical Polymers - Advanced Biomaterials and Biomedical Engineering and Drug Delivery System, Kagoshima University, Japan, April, (1995).

 

PATENTS

·         C. Rohloff, G. Chen, Z. Ding, S. Berry, L. Narayanan, M. Desjardin, Complexation of metal ions with polypeptides, US20070015689 A1, 20070118

·         Z. Ding, L. Kleiner, Minimization of drug oxidation in drug irradiated excipients formulations, US20050158379 A1, 20050721

 

Professional Presentations

·         Z. Ding, G. Ciambrone, L. Ponomarenko, and  H. Bentz, Development of methods to quantitate nasal delivery of proteins directly to the brain, a poster at ALZA Technology Summit, Nov. 17, 2005

·         Z. Ding, G. Chen, and H. Wang,  Macroporous hydrogel particles for tissue engineering, a poster at ALZA Technology Summit, Nov. 17, 2005

·         G. Chen, Z. Ding, L. Kang, P. Houston, L. Ponomarenko, and H. Bentz,  Injectable in situ forming scaffold for bone regeneration, a poster at ALZA Technology Summit, Nov. 17, 2005

·         Z. Ding, C. J. Long, E. V. Bulmus, P. S. Stayton and A. S. Hoffman, Temperature modulation of Biotin Binding, 25th Annual Meeting of Society for Biomaterials in conjunction with the 31st International Biomaterials Symposium, Providence, RI, (1999).

·         Z. Ding, G. Chen and A. S. Hoffman, V. Shetty, and C. N. Bertolami, Thermally-reversible polymer-antibody conjugates, 21st Annual Meeting of the Society for Biomaterials, San Francisco, CA, (1995).

·         Z. Ding, G. Chen and A. S. Hoffman, Activity and thermally-induced precipitation of poly(NIPAAm)-Enzyme conjugates, Division of Biochemical Technology-165, 207th ACS National Meeting, San Diego, CA (1994).

·         Z. Ding and Z. Ma, Study on New Thermal-responsive Hydrogel, The 5th China-Japan Bilateral Symposium on Radiation Chemistry, Beijing, China, Oct. (1991).

·        Z. Ding and M. Wu, Grafting of Condensed Ethylene Glycol Acrylate by Pre-irradiation ¾ Study on Effect of Molecular Weight of Oligomer on Grafting Reaction, Guiling International Symposium on Biomaterials and Fine Polymers, 201-202, Guiling, China, Oct. (1991).

·        Z. Ding, Q. Yan and Z. Ma, The Effect of Radiation Grafting on Drug Release of Silicone Rubber Ring, The 4th Japan-China Bilateral Symposium on Radiation Chemistry, Kyoto, Japan, April (1989).