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CURRICULUM VITAE

Wei-Chiang Shen

PERSONAL INFORMATION Business Address University of Southern California School of Pharmacy 1985 Zonal Avenue Los Angeles, California 90089-9121 Business Telephone (323) 442-1902 FAX (323) 442-1390 or 442-2263 e-mail [email protected] Home Address 2030 Robin Road San Marino, CA 91108 Home Telephone (626) 309-0613 Place of Birth China Citizenship United States of America (naturalized in 1976) Marital Status Married to Daisy Shen, two sons (Howard Shen and Jerry Shen)

EDUCATION 1965 - Department of Chemistry, Tunghai University, Taichung, Taiwan (Bachelor

of Science) 1972 - Department of Chemistry, Boston University, Boston, Massachusetts (Ph.D.,

Major in Bio-organic Chemistry) 1973 - Department of Biological Chemistry, Harvard Medical School, Boston,

Massachusetts (Postdoctoral Fellow).

ACADEMIC APPOINTMENTS

2006-present - John A. Biles Professor in Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles

1992-2006 - Professor of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles

1987-92 - Associate Professor of Pharmacy, School of Pharmacy, University of Southern California, Los Angeles

1983-87 - Associate Professor of Pathology and Pharmacology, School of Medicine, Boston University, Boston

1980-83 - Associate Research Professor of Pathology and Pharmacology, School of Medicine, Boston University, Boston

1976-80 - Assistant Research Professor of Pathology and Pharmacology, School of Medicine, Boston University, Boston

1973-76 - Senior Research Associate, Biochemistry Department, Brandeis University, Waltham, Massachusetts

Curriculum Vitae, Wei-Chiang Shen Page .

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ACADEMIC ADMINISTRATIVE APPOINTMENTS

2015-2017 - Associate Dean for Research, University of Southern California School of

Pharmacy

2003-2006 - Interim Chair, Department of Pharmaceutical Sciences, University of Southern California School of Pharmacy

1993-2000 - Vice-Chair, Department of Pharmaceutical Sciences, University of Southern California School of Pharmacy

1989-1992 - Director of Graduate Affairs, University of Southern California School of Pharmacy

OTHER PROFESSIONAL EXPERIENCE

2015- - Member, Advisory Committee, Xiang-Ming International Institute of Life & Health Science, Jiangsu University, China

2008-2012 - Scientific Advisor, Irish Drug Delivery Research Network, Ireland. 2007- - Visiting Professor, School of Pharmacy, Lanzhou University, China. 2004-2005 - President, Chinese-American Faculty Association of Southern California. 2000-2009 - Member, United States Pharmacopeial (USP) Convention.

2000-2003 - Member, Biological Safety Committee, University of Southern California. 2000 - Member and Interim Chair, Appointment, Promotion and Tenure Committee,

University of Southern California School of Pharmacy. 1999-2004 - Member, FDA Radioactive Drug Research Committee #36. 1998-1999 - Chair, University Patents and Technology Transfer Committee, University of Southern California. 1997-1998 - Chair, Appointments, Promotions, and Tenure Committee, University of Southern California School of Pharmacy. 1997 - Visiting Professor, School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.

1996- - Member, Committee on Faculty Tenure & Privileges Appeals, University of Southern California.

1996-1998 - Member, University Research Committee, University of Southern California. 1986 - Visiting Professor, Department of Pathology, North China Coal Medical

College, Hebei, China. 1979-86 - Visiting Lecturer in Biochemical Toxicology, Department of Biochemistry,

Brandeis University, Waltham, Massachusetts. 1983-84 - Principal, Newton Chinese Language School, Newton, Massachusetts.

AWARDS/HONORS Tunghai University Distinguished Alumni Award, 2011. Achievement Award, Chinese-American Faculty Association of Southern California, 2009. John A. Biles Professorship, USC School of Pharmacy, 2006. Distinguished Alumni Lecturer, Tunghai University, Taichung, Taiwan, 2003. Eurand Award (Grand Prize) for Outstanding Novel Research in Oral Drug Delivery, 2002. Fellow, American Association for the Advancement of Science (AAAS), elected 2000. Fellow, American Association of Pharmaceutical Scientists (AAPS), elected 1992. Cancer Research Scholar Award, American Cancer Society (Massachusetts Division), 1982-85.


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Postdoctoral Research Fellowship, Massachusetts Heart Association, 1972-73. Listed in "American Men and Women of Science" and "Marquis Who's Who in America”. Graduate students as recipients of the Graduate Student Award in AAPS National Meetings: Jason Wan (1992), Deven Shah (1994), Cindy Xia (2000), Jennica Zaro (2003), Yun Bai

(2004), Liyun Yuan (2006), Robert Mo (2011) and Yan Wang (2011).

EDITORIAL BOARD 1995-2005 -Editorial Advisory Board, Pharmaceutical Research 1993- -Editorial Board, Journal of Drug Targeting

JOURNAL REFEREE

American Journal of Physiology, Analytical Biochemistry, Archieves of Biochemistry and Biophysics, Biochemical Pharmacology, Biochemistry, Biochimica et Biophysica Acta, Bioconjugate Chemistry, Cancer Research, CRC Critical Review, Diabetes, Drug Discovery Today, European Journal of Pharmaceutics and Biopharmaceutics, FASEB Journal, Immunology Letters, International Journal of Pharmaceutics, International Journal of Cancer, Journal of American Chemical Society, Journal of Cellular Physiology, Journal of Controlled Release, Journal of Drug Targeting, Journal of Medicinal Chemistry, Journal of Peptide Research, Journal of Pharmaceutical Sciences, Journal of Pharmacology and Experimental Therapeutics, Medicinal Research Reviews, Molecular Pharmaceutics, Pharmaceutical Research.

GRANT REVIEWER

National Institutes of Health, USA National Science Foundation, USA Medical Research Council of Canada North Carolina Biotechnology Center National Health and Medical Research Council of Australia Science Foundation Ireland Maryland Technology Enterprise Institute Frontier and Innovative Research Project, National Taiwan University, Taiwan Israel Science Foundation US-Israel Binational Science Foundation Estonian Science Foundation Hungarian Scientific Research Fund Wellcome Trust, UK Samantha Dickson Brain Tumour Trust, UK Philip Morris External Research Program Juvenile Diabetes Research Foundation International (JDRF)

PROFESSIONAL AND HONOR SOCIETIES American Association for the Advancement of Science (Fellow) American Association of Pharmaceutical Scientists (Fellow)


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Controlled Release Society Phi Tau Phi Scholastic Honor Society of America Rho Chi Pharmacy Honor Society Society of Chinese Bioscientists in America

EXTERNAL DOCTORAL DISSERTATION EXAMINER

1986 Dalhousie University, Halifax, Nova Scotia, Canada 1994, 2000 University of the Witwatersrand, Johannesburg, South Africa 2002, 2007 National University of Singapore, Singapore 2014 China Pharmaceutical University, China 2015 National Taiwan University, Taiwan

PREVIOUS GRADUATE STUDENTS AND FELLOWS

Name Degree Year Current position

Postdoctoral fellows and visiting scholars:

Daming Yang MD 1984 Practice medicine in New York City Wande Li MD 1985 Faculty, Boston Univ. School of Med. Stefano Persiani Ph.D. 1990 Director, Rotta Research Lab, Italy Xiangtang Du Ph.D. 1999 Faculty, Henan Medical Univ, China Donald Chow Ph.D. 1999 Unidose Systems Co., CA Hashem Heiati Ph.D. 1999 Favrille, Inc., CA Jeff Wang Ph.D. 2000 Faculty, Western University of Health

Sciences, Pomona, CA Jun Wu Ph.D. 2001 Scientist, City of Hope Medical Center Yuanjing Qi Prof. 2005 Professor, Shandong, China Jingman Ni Ph.D. 2006 Professor, Lanzhou University, China Qing Xia M.D. 2010 Associate Professor, Peking University

Keisuke Oda Ph.D. 2011 Assistant Professor, Hiroshima Univ. Shanshan Tong Ph.D. 2015 Associate Professor, Jiangsu Univ

Ph.D. students:

Edward Feener Ph.D. 1989 Faculty, Harvard Medical School Jason Wan Ph.D. 1992 CEO, Sinotherapeutics, Shanghai, China Hossein Ekrami Ph.D. 1994 Surza’s Medical Investment Group Aaron Yeung Ph.D. 1995 Church Minister, Hawaii Deven Shah Ph.D. 1995 Senior Director, GalaxoSmithKline Mitchell Taub Ph.D. 1996 Director, Boehringer-Ingelheim Cindy Xia Ph.D. 2000 Director, Takeda USA Adam Widera Ph.D. 2003 Director, Grifols Rita Shen Ph.D. 2005 Dean, Natl Taiwan U School of Pharm Jennica Zaro Ph.D. 2005 Faculty, West Coast U School of Pharm Tinten Lim Ph.D. 2005 Senior Scientist, Nanotrope Yun Bai Ph.D. 2006 Faculty, PCOM School of Pharmacy Maureen Barnes Ph.D. 2006 Senior Scientist, Biogen-Idec Fariba N. Cooper Ph.D. 2006 Research Scientist, Eli Lilly Leena Patel Ph.D. 2007 Scientific Writer, Allergan Pharm


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Rana Bahhady Ph.D. 2007 Practice Pharmacy Liyun Yuan M.D.; Ph.D. 2007 Faculty, USC Keck School of Medicine Nurmamet Amet Ph.D. 2008 Principle Scientist, Pfizer Inc. Xiaoying Chen Ph.D. 2011 Principle Scientist, Pfizer Inc. Randall Kenien Ph.D. 2012 Olympus Robert Mo Ph.D. 2012 Associate Director, Akebia Ther, MA Yan Wang Ph.D. 2012 Scientist, Amgen Likun (Paul) Fei Ph.D. 2014 Senior Scientist, Intrexon, SD, CA Juntang Shao Ph.D. 2016 Senior Scientist, Boehringer-Ingelheim Yu-Sheng Chen Ph.D. 2016 Postdoctoral Fellow, U CT Johnson Inst

MS students:

Yi-Jing Lin MS 1990 Returned to Taiwan Krishna Srivastava MS 1992 Family business (India) Laura Honeycutt Pham.D./MS 1999 Pharmacist (Pittsburgh) Karin Beloussow MS 1999 Scientific Writer, Amgen Li Wang MS 2000 Pharmacist (Los Angeles) Daphne Wu MS 2001 Ph.D. Student, UC Davis Wendy Lin MS 2003 Phoenix Pharmaceutics (California) Chris Hsu MS 2004 Ph.D. Student, Tsinghua Univ. (Taiwan) Claire Lai MS 2006 Ph.D. Student, Taipei Medical Univ. Jacqueline E. Vekich MS 2006 Genentech, Oceanside, CA Hsin-Fan Lee MS 2008 Res. Assistant, USC Ling (Michelle) Ren MS 2009 Medical Instrument Business Matthew A. Janson MS 2009 Amgen Max Kuo MS 2010 Project Manager, Mello Biotech Yu-Sheng (Sam) Chen MS 2011 Ph.D. student, USC Manali Shah MS 2012 Clinical Trial Coordinator, UCLA Hsuan-Yao Wang MS 2014 Ph.D. student, USC Xinru Qiu MS 2015 Color Genomics, San Diego

Current Ph.D. students: Zoe Folchman-Wagner Yuqian Liu Li Zhou Hsuan-Yao Wang

Visiting students:

Fariba Nouroziyan (Uppsala University, Sweden), 2000. Thuy Tran (Uppsala University, Sweden), 2005. Christina Schlesinger (UC Berkeley), 2011. Julia Nilsson (Lund’s Institute of Technology, Sweden), 2011 – 2012. Chunmeng Sun (China Pharmaceutical University, China), 2011 – 2014. Tze-Harn Yeh (National Taiwan University, Taiwan), 2013-2015. Arthur Leclercq (Polytech Clerment-Ferrand, France), 2015. Qiuwen Zhu (China Pharmaceutical University, China) 2015. Kang Sun (China Pharmaceutical University, China) 2016.


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CURRENT RESEARCH INTERESTS 1. Endocytosis and intracellular processing of macromolecules in mammalian cells.

2. Transferrin receptor-mediated transcytosis in epithelial cells. 3. Reversible aqueous lipidization (REAL) of polypeptides and oligonucleotides 4. Oral and pulmonary delivery of peptide and protein drugs. 5. Design of recombinant fusion proteins for therapeutic applications. 6. Cell-penetrating peptides (CPPs): mechanisms and applications. 7. CPP-mediated siRNA delivery. 8. Proinsulin-Transferrin fusion protein as a liver-targeted insulin analog for diabetes treatment.

INVITED SPEAKER IN RECENT NATIONAL AND INTERNATIONAL CONFERENCES

(2001 - PRESENT) “Reversible lipidization of peptides and proteins.” Conference on Barriers to Entry: New

Directions in Drug Delivery Systems, Los Angeles, CA, March, 2001.

“Transferrin receptor-mediated transcytosis for oral delivery of insulin.” 28th International Symposium on Controlled Release of Bioactive Materials, San Diego, CA, June, 2001. “Reversible aqueous lipidization of peptide drugs.” US-Japan Conference on Drug Development and Rational Drug Therapy, Tokyo, Japan, August, 2001.

“Transferrin receptor-mediated transcytosis for oral delivery of insulin.” Symposium on Oral Delivery Technologies for Biopharmaceutical Products, Industrial Technology Research Institute, Hsin-Chu, Taiwan, November, 2001.

“Reversible lipidization for oral delivery of peptide drugs.” Symposium on Oral Delivery

Technologies for Biopharmaceutical Products, Industrial Technology Research Institute, Hsin-Chu, Taiwan, November, 2001.

“Transferrin Receptor Mediated Transport in GI Absorption.” AAPS Pharmaceutics and Drug

Delivery Conference, Arlington, VA, April, 2002. “Reversible lipidization for oral delivery of peptide drugs.” 29th Annual Meeting of the

Controlled Release Society, Seoul, Korea, July, 2002.

“Transferrin Receptor-Mediated Transcytosis for Pulmonary Drug Delivery.” Nasal and Pulmonary Drug Delivery Conference VII, Barcelona, Spain, September, 2003. “Recombinant Transferrin Fusion Proteins for Oral Delivery of Protein Drugs.” 2nd Forum on Cross-Straits Chemical Biology, Biotechnology and Medicine Development, Xiamen, China, July, 2004. “Membrane Transduction Peptides as Potential Carriers for Cytoplasmic Delivery of Macromolecular Drugs.” 10th SCBA International Symposium, Beijing, China, July, 2004.


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“Recombinant Transferrin Fusion Proteins for Oral Delivery of Protein Drugs.” U.S./Taiwan Nutraceutical, Medical, Biotech, and Genomics Conference, Pasadena, CA, October, 2004. “Membrane Transduction Peptides as Potential Carriers for Cytosolic Delivery of Macromolecular Drugs.” 3rd Forum on Cross-Straits Chemical Biology, Biotechnology and Medicine Development, Taichung, Taiwan, July, 2005. “Recombinant Transferrin-G-CSF Fusion proteins as Oral Myelopoietic Agents.” 2006 International Conference in Biotech and Pharmaceutical Science and Technology, San Diego, CA, December, 2006. “Oral Delivery of Recombinant Transferrin-Fusion Proteins.” 13th International Symposium on Recent Advances in Drug Delivery Systems, Salt Lake City, UT, February, 2007. “Design of Recombinant Transferrin-Granulocyte Colony-Stimulating Factor Fusion Proteins for Oral Delivery.” GEM4 Conference on Cancer, Singapore, July, 2007. “Cell Penetrating Peptides as Vectors for Pulmonary Delivery of Insulin.” Biomedical Engineering Society 2007 Annual Fall Meeting, Los Angeles, CA, September, 2007. “Design of Recombinant G-CSF-Transferrin Fusion Protein for Oral Delivery.” 7th International Conference and Workshop on Biological Barriers and Nanomedicine, Saarbrueken, Germany, February, 2008. “Reversible Aqueous Lipidization (REAL) of Peptide and Protein Drugs.” BIT’s First Annual Protein and Peptide Conference (PepCon2008), Shenzhen, China, April, 2008. “Design of Recombinant G-CSF-Transferrin Fusion Proteins for Oral Delivery.” 3rd Annual Engineering Protein Therapeutics for Delivery, PEGS Conference, Boston, MA, May, 2008. “Protein and Peptide Drug Delivery: An 85 Year Old Challenge to the New Generation of Drugs from Pharmaceutical Industry.” Monte Jade Science and Technology Association Bio Forum, Santa Clara, CA, May, 2008. “Reversible Lipidized Interferon-alpha as an Anti-Hepatitis Drug.” 5th Conference of Channel-Bridge Chemistry, Biology and Material Science, Tainan, Taiwan, July, 2008. “Reversible Lipidization of Protein and Peptide Drugs: A Study of Lipidized Interferon-alpha.” Drug Delivery Technology Asia 2008, Seoul, South Korea, October, 2008. “Cell-Penetrating Peptides: from Peptide Chemistry to Drug Delivery.” Symposium in Honor of Professor Richard A. Laursen, Boston University, Boston, October, 2009.

“Effect of Spacer Insertion on the Production, Biological Activity, and Pharmacokinetics of Recombinant Bifunctional Fusion Proteins.” CHI PepTalk Conference, San Diego, January, 2010. “Recombinant Granulocyte Colony-Stimulating Factor and Transferrin Fusion Proteins as Myelopoietic Agents.” PepCon 2010, Beijing, China, March, 2010. “Production, Pharmacokinetics and Oral Delivery of Bifunctional Transferrin Fusion Proteins.” Novo Nordisk Oral Protein Delivery Symposium, Copenhagen, Denmark, December, 2010.


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“Recombinant Transferrin fusion Proteins for the Activation of Protein Precursors in Liver: The Conversion of Proinsulin to Insulin as a Transferrin Fusion Protein in Hepatoma Cells.” CHI PepTalk Conference, San Diego, January, 2011. “Cell-Penetrating Peptides for Cytosolic or Nuclear Transport.” PepCon 2011, Beijing, China, March, 2011. “Pharmacokinetics of Recombinant Bifunctional Fusion Proteins.” Gordon Research Conference – Drug Metabolism, Holderness, New Hampshire, July, 2011.

“Fusion Proteins for Improving Absorption and Disposition of Protein Drugs: Transferrin as an Active Carrier Domain.” AAPS Annual Meeting, Washington, DC, October, 2011. “Pharmacokinetics and pharmacodynamics of Recombinant Bifunctional Fusion Proteins.” 2nd Annual World Congress of Molecular and Cell Biology, Beijing, China, May, 2012. “Recombinant Proinsulin-Transferrin Fusion Protein as an Insulin Prodrug for the Selective Inhibition of Hepatic Glucose Production.” CHI PepTalk Conference, Palm Springs, January, 2013.

“Effect of Linker on Pharmacokinetics and Pharmacodynamics of Bifunctional Fusion Proteins.” PepCon-2013, Suzhou, China, March, 2013. “Recombinant Proinsulin-Transferrin Fusion Protein as an Insulin Prodrug for the Selective Inhibition of Hepatic Glucose Production.” Pharmaceutica-2013, Chicago, April 2013. “Recombinant Proinsulin-Transferrin Fusion Protein as a Model of Peptide Prodrug for the Selective Activation in the Liver.” AAPS National Biotech Conference, San Diego, May 2013. “Recombinant Proinsulin-Transferrin Fusion Protein for the Treatment of Diabetes.” The 6th China Medicinal Biotech Forum, Shenzhen, China, September 26th, 2013. “The Design, Expression and Characterization of Fusion Peptides and Proteins.” AAPS National Biotech Conference, San Diego, May 20th, 2014. “Highly pH-Sensitive Cell-Penetrating Peptides as Tumor Targeting Macromolecular Carriers.” BIT’s 4th Annual World Congress of Nano Science & Technology, Qingdao, China, Oct. 29th, 2014. “Cell-Penetrating Peptides in Drug Delivery.” PepCon-2015, Nanjing, China, Apr. 26th, 2015. “Recombinant proinsulin-transferrin fusion protein for liver-targeted insulin therapy.” SCBA International Symposium, Taipei, Taiwan, Jun. 27th, 2015. “Proinsulin-transferrin fusion protein as a long-lasting and liver-targeted insulin analog.” PepTalk-2016, San Diego, CA, Jan. 18th, 2016. “Highly pH-Sensitive Cell-Penetrating Peptides as Carriers of Macromolecular Drugs Targeted to Solid Tumors.” China Pharmaceutical Conference, Nanjing, China, Nov. 19th, 2016.


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INVITED SEMINAR PRESENTATIONS

2005: Pfizer, Inc., St. Louis, MO, June 14. Tunghai University, Taiwan, July 19. Industrial Technology Research Institute, Taiwan, July 25. National Taiwan University, Taiwan, July 27. National Defense Medical Center, Taiwan, July 28. Wyeth Pharmaceuticals, Cambridge, MA, August 10. University of California, Irvine, CA, October 10. China Pharmaceutical University, China, November 4.

2006: Boston University, Boston, MA, May 10. Hoffman La Roche, Inc., Nutley, NJ, September 1. University of Tennessee, Memphis, TN, October 16.

2007: National Tsinghua University, Taiwan, January 17. National Taiwan University, Taiwan, January 22. City of Hope Medical Center, Duarte, CA, March 8. Pfizer, Inc., St. Louis, MO, March 16. Amylin Pharmaceuticals, Inc. La Jolla, CA, August 17. Ohio State University, Columbus, OH, October 9. Jiangsu University, China, October 15. China Pharmaceutical University, China, October 17. Lanzhou University, China, October 22. Allergan, Inc., Irvine, CA, December 4.

2008: Bath University, Bath, UK, March 3. Cardiff University, Cardiff, UK, March 5. Wheaton College, Norton, MA, October 3. National Taiwan University, Taiwan, October 27.

2009: Genentech, South San Francisco, CA, January 28. University of North Carolina, Chapel Hill, NC, March 18. Trinity College, Dublin, Ireland, April 24. Pfizer, Inc., St. Louis, MO, November 18.

2010: National Defense Medical Center, Taiwan, March 19. Peking University, Beijing, China, March 22. China Pharmaceutical University, China, May 17. Trinity College, Dublin, Ireland, July 5.

2011: University of Massachusetts, Amherst, MA, March 3. Fudan University School of Pharmacy, Shanghai, China, March 28. University College Dublin, Dublin, Ireland, October 18.


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2012: Liaocheng Hospital Medical Center, Shandong, China, May 14. Taipei Medical University, Taipei, Taiwan, June 4. National Taiwan University, Taipei, Taiwan, October 29. Taipei Medical University, Taipei, Taiwan, Oct. 30.

2013: AAPS Southern California Pharmaceutical Discussion Group, Irvine, February 21. University of North Carolina, Chapel Hill, NC, April 15. University of Macau, Macau, September 24. Ventria Biosciences, Fort Collins, CO, October 15.

2014: Diabetes and Obesity Research Institute, USC, March 27. Joslin Diabetes Center, Harvard Medical School, Boston, MA, April 22.

2015: Beijing University School of Pharmacy, Beijing, China, December 4. Tianjin Medical University School of Pharmacy, Tianjin, China, December 7.

2016: University of Nebraska School of Pharmacy, Omaha, NE, April 1. Western University of Health Sciences, College of Pharmacy, Pomona, CA, April 28. AskGene Pharmaceuticals, Camarillo, CA, May 31.

INVENTIONS AND PATENTS US Patent No. 4,631,190: "Acidity-Sensitive Spacer Molecule to Control the Release of

Pharmaceuticals from Molecular Carriers." US Patent No. 5,144,001: "Acidity-Sensitive Spacer Molecule to Control the Release of

Pharmaceuticals from Molecular Carriers." US Patent No. 4,701,521: "Method of Effecting Cellular Uptake of Molecules." US Patent No. 4,847,240: "Method of Effecting Cellular Uptake of Molecules." US Patent No. 5,254,342: "Compositions and Methods for Enhanced Transepithelial and

Transendothelial Transport of Active Agents." US Patent No. 5,907,030: "Methods and Compositions for Lipidization of Hydrophilic

Molecules." US Patent No. 5,936,092: “Methods and Compositions for Lipidization of Hydrophilic

Molecules.” US Patent No. 6,093,692: “Methods and Compositions for Lipidization of Hydrophilic

Molecules.”


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US Patent No. 6,225,445: “Methods and Compositions for Lipidization of Hydrophilic Molecules.”

US Patent No. 6,590,071: “Reversible Aqueous pH Sensitive Lipidization Reagents,

Compositions and Methods of Use.” US Patent No. 7,052,704: “Methods and Compositions for Lipidization of Hydrophilic

Molecules.” US Patent No. 7,943,733: “Spacers to Increase the Expression of Recombinant Fusion Proteins.” US Patent No. 7,956,158: “Fusion Proteins with Cleavable Spacers and Uses Thereof.” US Patent No. 8,188,032: “G-CSF-Transferrin Fusion Proteins.” US Patent No. 8,378,076: “Spacers to Increase the Expression of Recombinant Fusion Proteins.” US Patent No. 8,486,384: “Lipidized interferon and methods of treating viral hepatitis.” US Patent Pending No. PCT/US13/174,520: “Methods for Uses of Protein Precursors as

Prodrugs.” US Provisional Appln No. 61/754,448: “Design of pH-sensitive Oligopeptide Complexes for

Drug Release under Mildly Acidic Conditions.” US Provisional Appln No. 62/396,019: “Single Chain Fc-Dimer-Human Growth Hormone

Fusion Protein for Improved Drug Delivery.”


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PUBLICATIONS

Research papers:

1. Wang TSC, Liang YC and Shen WC: Method of extraction and analysis of higher fatty acids and triglycerides in soils. Soil Sci 107:181-187, 1969.

2. Laursen RA, Baumann JB, Linsley KB and Shen WC: Inactivation of fumarase by bromomesaconate, an active site-directed irreversible inhibitor. Arch Biochem Biophys 130:688-689, 1969.

3. Laursen RA, Shen WC and Zahka KG: Bromomesaconic and bromocitraconic acids. Potential Active Site Labeling Reagents for Dicarboxylic Acid Metabolizing Enzymes. J Med Chem 14:619-621, 1971.

4. Shen WC, Mauck L and Colman RF: Physicochemical properties of the DPN- specific isocitrate dehydrogenase of pig heart. J Biol Chem 249:7942-7949, 1974.

5. Shen WC and Van Vunakis H: Nicotine and its metabolites IV. Formation of the nicotine analogue of DPN by pig brain DPNase. Res Commun Chem Pathol Pharmacol 9:405-412, 1974.

6. Shen WC and Van Vunakis H: The formation and characterization of the nicotine analog of triphosphopyridine nucleotide. Biochemistry 13:5362-5367, 1974.

7. Shen WC and Colman RF: Cyanate modification of essential lysyl residues of the DPN-specific isocitrate dehydrogenase of pig heart. J Biol Chem 250:2973-2978, 1975.

8. Shen WC, Franke J and Van Vunakis H: Nicotinamide nucleotide analogues of nicotine and cotinine -- enzymic studies. Biochem Pharmacol 26:1835-1840, 1977.

9. Shen WC, Greene KM and Van Vunakis H: Detection by radioimmunoassay of nicotinamide nucleotide analogues in tissues of rabbits injected with nicotine and cotinine. Biochem Pharmacol 26:1841-1846, 1977.

10. Shen WC and Ryser H J-P: Conjugation of poly-l-lysine to albumin and horseradish peroxidase: A novel method of enhancing the cellular uptake of proteins. Proc Natl Acad Sci USA 75:1872-1876, 1978.

11. Ryser H J-P, Shen WC and Merk FB: Membrane transport of macromolecules: New carrier functions of proteins and poly(amino acids). Life Sci 22:1253-1260, 1978.

12. Ryser H J-P and Shen WC: Conjugation of methotrexate to poly(l-lysine) increases drug transport and overcomes drug resistance in cultured cells. Proc Natl Acad Sci USA 75:3867-3870, 1978.

13. Shen WC and Ryser H J-P: Poly(l-lysine) and poly(d-lysine) conjugates of methotrexate: Different inhibitory effect on drug resistant cells. Mol Pharmacol 16:614-622, 1979.

14. Ryser H J-P and Shen WC: Conjugation of methotrexate to poly(l-lysine) as a potential way to overcome drug resistance. Cancer 45:1207,-1211, 1980.


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15. Shen WC and Ryser H J-P: Selective protection against the cytotoxicity of methotrexate and methotrexate-poly(lysine) by thiamine pyrophosphate, heparin and leucovorin. Life Sci 28:1209-1214, 1981.

16. Shen WC and Ryser H J-P: Cis-aconityl spacer between daunomycin and macromolecular carrier: A model of pH-sensitive linkage releasing drug from a lysosomotropic conjugate. Biochem Biophys Res Commun 102:1048-1054, 1981.

17. Shen WC and Ryser H J-P: Poly(L-lysine) has different membrane transport and drug-carrier properties when complexed with heparin. Proc Natl Acad Sci USA 78:7589-7593, 1981.

18. Ryser H J-P, Drummond I and Shen WC: The cellular uptakes of horseradish peroxidase and its poly(lysine) conjugate by cultured fibroblasts are qualitatively similar despite a 900-fold difference in rate. J Cell Physiol 113:167-178, 1982.

19. Ryser H J-P, Morad N and Shen WC: Interaction of heparin with cultured cells: Possible role of fibronectin in uncoupling surface binding and endocytosis. Cell Biol Internat'l Reports 7:923-930, 1983.

20. Shen WC and Ryser H J-P: Selective killing of Fc-receptor-bearing tumor cells through endocytosis of a drug-carrying immune complex. Proc Natl Acad Sci USA 81:1445-1447, 1984.

21. Morad N, Ryser H J-P and Shen WC: Binding sites and endocytosis of heparin and poly(lysine) are changed when the two molecules are given as a complex to Chinese hamster ovary cells. Biochim Biophys Acta 801:117-126, 1984.

22. Shen WC, Yang D and Ryser H J-P: Colorimetric determination of microgram quantities of polylysine by trypan blue precipitation. Anal Biochem 142:521-524, 1984.

23. Shen WC, Ryser H J-P and LaManna L: Disulfide spacer between methotrexate and poly(D-lysine): A probe for exploring the reductive process in endocytosis. J Biol Chem 260:10905-10908, 1985.

24. Ballou B, Reiland JM, Levine G, Shen WC, Ryser H J-P, Solter D and Hakala TR: Tumor location and drug targeting using a monoclonal antibody (anti-SSEA-1) and antigen-binding fragments. J Surg Oncol 31:1-12, 1986.

25. Li W, Ryser H J-P and Shen WC: Altered endocytosis in a mutant of LM-fibroblasts defective in cell-cell fusion. J Cell Physiol 126:161-166, 1986.

26. Shen WC and Ryser H J-P: Disulfide and other spacers for the intracellular release of drugs from polymeric carriers. Polymer Preprints 27:9-10, 1986.

27. Ryser H J-P, Shen WC and Morad N: Poly(lysine): Heparin complexes as potential drug-carriers for receptor-mediated endocytosis. Polymer Preprints 27:15-16, 1986.

28. Shen WC, Ballou B, Ryser H J-P and Hakala TR: Targeting, internalization, and cytotoxicity of methotrexate-monoclonal anti-SSEA-1 antibody conjugates in cultured F-9 teratocarcinoma cells. Cancer Res 46:3912-3916, 1986.


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29. Ryser H J-P, Mandel R, Hacobian A and Shen WC: Methotrexate-poly (lysine) as a selective agent for mutants of Chinese hamster ovary cells defective in endocytosis. J Cell Physiol 135:277-284, 1988.

30. Ryser HJ-P, Li W, Mandel R and Shen WC: Stable variant of LM fibroblast defective in fluid-phase but competent in receptor-mediated endocytosis. J Cell Physiol 137:490-496, 1988.

31. Persiani S, Ballou B, Shen WC, Ryser HJ-P, Reiland JM and Hakala TR: In vivo antitumor effect of methotrexate conjugated to anti-SSEA-1 monoclonal IgM antibody on MH-15 mouse teratocarcinoma. Cancer Immunol Immunotherap 29:167-170, 1989.

32. Shen WC, Du X, Feener EP and Ryser HJ-P: The intracellular release of methotrexate from a synthetic drug carrier system targeted to Fc receptor-bearing cells. J Controlled Release 10:89-96, 1989.

33. Persiani S and Shen WC: Increase of poly(lysine) uptake but not fluid phase endocytosis in neuraminidase pretreated Madin-Darby canine kidney (MDCK) cells. Life Sci 45:2605-2610, 1989.

34. Du X, Yeung A and Shen WC: A cytostatic protein isolated from the conditioned medium of mouse monocytic leukemia WEHI-3 cell cultures. Immunol Lettrs 23:119-124, 1989.

35. Shen WC, Wan J and Shen D: Proteolytic processing in a non-lysosomal compartment is required for transcytosis of protein-polylysine conjugates in cultured Madin-Darby canine kidney cells. Biochem Biophys Res Commun 166:316-323, 1990.

36. Shen WC: Acid-sensitive dissociation between poly(lysine) and histamine-modified poly(glutamate) as a model for the drug-releasing from carriers in endosomes. Biochim Biophys Acta 1034:122-124, 1990.

37. Wan J, Persiani S and Shen WC: Transcellular processing of disulfide-and thioether-linked peroxidase polylysine conjugates in cultured MDCK epithelial cells. J Cell Physio 145:9-15, 1990.

38. Feener EP, Shen WC and Ryser HJ-P: Cleavage of disulfide bond in endocytosed macromolecules. J Biol Chem 265:18780-18785, 1990.

39. Shen WC, Wan J, Persiani S and Shen D: Poly(amino acids) as biodegradable carriers in transepithelial drug delivery systems. Polymer Preprints 31:163-164, 1990.

40. Shen WC, Persiani S and Srivastava K: Chemical linkages in drug-antibody conjugation. BioPharm 3(1):16-19, 1990.

41. Shen WC, Persiani S, Ballou B and Hakala TR: Antibodies as drug carriers for solid tumor: evaluation of drug-anti-SSEA-1 conjugates in the treatment of teratocarcinoma. Targeted Diagn Ther 3: 289-304, 1990.

42. Lin YJ and Shen WC: Effects of deoxycholate on the transepithelial transport of sucrose and horseradish peroxidase in filter-grown MDCK cells. Pharm Res 8:498-501, 1991.

43. Persiani S, Yeung A, Shen WC and Kennedy AR: Polylysine conjugates of Bowman-Birk protease inhibitor as targeted anticarcinogenic agents. Carcinogenesis 12: 1149-1152, 1991.


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44. Mandel R, Ryser HJP, Niaki B, Ghani F and Shen WC: Isolation of variants of chinese hamster ovary cells with abnormally low levels of GSH: Decreased ability to cleave endocytosed disulfide bonds. J Cell Physiol 149:60-65, 1991.

45. Taub M and Shen WC: Polarity in the transcytotic processing of apical and basal membrane-bound peroxidase-polylysine conjugates in MDCK cells. J Cell Physiol 150:283-290, 1992.

46. Wan J, Taub ME, Shah D and Shen WC: Brefeldin A enhances receptor-mediated transcytosis of transferrin in filter-grown Madin-Darby canine kidney cells. J Biol Chem 267:13446-13450, 1992.

47. Ballou B, Jaffe R, Persiani S, Shen WC, Langone JJ, Sands H, Reidland JM, Curley J and Hakala TR: Tissue localization of methotrexate-monoclonal-IgM immunoconjugates: anti-SSEA-1 and MOPC 104E in mouste teratocarcinomas and normal tissues. Cancer Immunol Immunother 35:251-254, 1992.

48. Ekrami H, Kennedy AR, Witschi H and Shen WC: Cationized Bowman-Birk protease inhibitor as a targeted cancer chemopreventive agent. J Drug Targeting 1:41-49, 1993

49. Taub ME and Shen WC: Regulation of pathways within cultured epithelium cells for the transcytosis of basalmembrane-bound peroxidase-polylysine conjugate. J Cell Sci 106:1313-1321, 1993.

50. Shah D and Shen WC: The establishment of polarity and enhanced transcytosis of transferrin receptors in enterocyte-like caco-2 cells. J Drug Targeting 2:93-99, 1994.

51. Taub ME, Wan J and Shen WC: Transepithelial transport of tyramine across filter-grown MDCK cells via a poly (D-lysine) carrier. Pharm Res 11:1250-1256, 1994.

52. Ekrami H and Shen WC: Carbamylation decreases the cytotoxicity but not the drug-carrier properties of polylysines. J Drug Targeting 2:469-475, 1995.

53. Ekrami H, Kennedy AR and Shen WC: Disposition of positively changed Bowman-Birk protease inhibitor conjugates in mice: Influence of protein conjugate charge density and size on lung targeting. J Pharm Sci 84:456-461, 1995.

54. Gladysheva IP, Polekhina OV, Shen WC, Shevchenko AA, Kazanskaya NF and Larionova NI: Structure and biological properties of Bowman-Birk soybean proteinase inhibitor conjugate with block copolymer of ethylene oxide and propylene oxide. Biochemistry (Moscow) 60:385-391, 1995.

55. Ekrami HM, Kennedy AR and Shen WC: Water soluble fatty acid derivatives as acylating agents for reversible lipidization of polypeptides. FEBS Lett 371:283-286, 1995.

56. Shah D and Shen WC: The paradox of transferrin receptor-mediated drug delivery - intracellular targeting or transcellular transport? J Drug Targeting 3:243-245, 1995.

57. Honeycutt L, Wang J, Ekrami H and Shen WC, Comparison of pharmacokinetic parameters of a polypeptide, the Bowman-Birk protease inhibitor (BBI), and its plamitic acid conjugate. Pharm Res 13:1372-1376, 1996.


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58. Shah D and Shen WC, Transepithelial delivery of an insulin-transferrin conjugate in enterocyte- like Caco-2 cells. .J Pharm Sci, 85:1306-1311, 1996.

59. Hamm-Alvarez SF, Sonee M, Loran-Goss K and Shen WC, Paclitaxel and nocodazole differentially alter endocytosis in cultured cells. Pharm Res 13:1647-1656, 1996.

60. Yeung AK, Basu SK, Wu SK, Chun C, Okamoto CT, Hamm-Alvarez S, von Grafenstein H, Shen

WC, Kim KJ, Bolger MB, Haworth IS, Ann DK and Lee VHL: Molecular identification of a role for tyrosine 167 in the function of the human inestinal proton-coupled dipeptide transporter (hPepT1) Biochem Biophys Res Commun 250: 103-107, 1998.

61. Wang J, Shen D and Shen WC: Preparation, purification, and characterization of a reversibly lipidized desmopressin with potentiated anti-diuretic activity. Pharm Res 16: 1674-1679, 1999.

62. Wang J and Shen WC: Gastric retention and stability of lipidized Bowman-Birk protease inhibitor in mice. Int J Pharm 204: 111-116, 2000.

63. Xia, C, Wang J and Shen WC: Hypoglycemic effect of insulin-transferrin conjugate in streptozotocin-induced diabetic rats. J Pharmacol Exp Ther 295: 594-600, 2000. (PMID 11046093).

64. Shen WC, Beloussow K, Meirim MG, Neuse EW and Caldwell G: Antiproliferative activity of polymer-bound, monoamine-coordinated platinum complexes against LNCaP human metastatic prostate adenocarcinoma cells. J Inorg Organometal Polym 10: 51-60, 2000.

65. Caldwell G, Meirim MG, Neuse EW, Beloussow K and Shen WC: Antiproliferative activity of polyaspartamide-ferrocene conjugates containing the biofissionable carboxamide function in the anchoring links. J Inorg Organometal Polym 10: 93-101, 2000.

66. Xia C and Shen WC: Tyrphostin-8 enhances transferrin receptor-mediated transcytosis in Caco-2 cells and increases hypoglycemic effect of orally administered insulin-transferrin conjugate in diabetic rats. Pharm Res 18: 191-195, 2001. (PMID 11405290).

67. Du X, Beloussow K and Shen WC: Bowman-Birk protease inhibitor and its palmitic acid conjugate prevent 7,12-dimethylbenz[a]anthracene-induced transformation in cultured mouse mammary glands. Cancer Lett 164: 135-141, 2001.

68. Gladysheva IP, Polekhina OV, Karmakova TA, Nemtsova ER, Yakubovskaya RI, Shen WC, Kennedy AR and Larionova NI: Potential of block copolymer- and imuno-conjugates for tumor-targeted delivery of Bowman-Birk soybean proteinase inhibitor. J Controlled Release 74: 303-308, 2001.

69. Beloussow K, Wang L, Wu J, Ann D and Shen WC: Recombinant arginine deiminase as a potential anti-angiogenic agent. Cancer Lett 183: 155-162, 2002.

70. Wang J, Wu D and Shen WC: Structure-activity relationship of reversibly lipidized peptides: Studies of fatty acid-desmopressin conjugates. Pharm Res 19: 609-614, 2002.

71. Widera A, Beloussow K, Kim KJ, Crandall ED and Shen WC: Phenotype-dependent synthesis of transferrin receptor in rat alveolar epithelial cell monolayers. Cell Tissue Res 312: 313-318, 2003.


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72. Shen LJ, Lin WC, Beloussow K and Shen WC: Resistance to the anti-proliferative activity of recombinant arginine deiminase in cell culture correlates with the endogenous enzyme, argininosuccinate synthetase. Cancer Lett 191: 165-170, 2003.

73. Larionova NV, Malykh EV, Villemson AL, Krasota AJu, Duchene D, Ollivon M, Gernet M,

Belousova RV, Shen WC and Larionova NI: Effect of membranotropic and mucoadhesive formulations of protein proteinase inhibitors on bovine herpes virus-1 reproduction. Int J Pharm 256: 191-198, 2003.

74. Wang J, Chow D, Heiati H and Shen WC: Reversible lipidization for the oral delivery of salmon calcitonin. J Controlled Release 88: 369-380, 2003.

75. Shen LJ, Lin WC, Beloussow K, Hosoya K, Terasaki T, Ann DK and Shen WC: Arginine deiminase inhibits NO production via iNOS, but not eNOS in endothelial cells. Biochem Pharmacol 66: 1945-1952, 2003.

76. Widera A, Kim KJ, Crandall ED and Shen WC: Transcytosis of GCSF-transferrin across rat alveolar epithelial cell monolayers. Pharm Res 20: 1231-1238, 2003.

77. Zaro JL and Shen WC: Quantitative comparison of membrane transduction and endocytosis of oligopeptides. Biochem Biophys Res Commun 307: 241-247, 2003.

78. Kennedy AR, Kritchevsky D and Shen WC: Effects of spermine-conjugated Bowman-Birk inhibitor (spermine-BBI) on carcinogenesis and cholesterol biosynthesis in mice. Pharm Res 20: 1908-1910, 2003.

79. Widera A, Bai Y and Shen WC: The transepithelial transport of a G-CSF-transferrin conjugate in Caco-2 cells and its myelopoietic effect in BDF1 mice. Pharm Res 21: 278-284, 2004. (PMID 15032309).

80. Lim CJ and Shen WC: Transferrin-oligomers as potential carriers in anti-cancer drug delivery. Pharm Res 21: 1985-1992, 2004.

81. Shen LJ, Beloussow K and Shen WC: Accessibility of endothelial and inducible nitric oxide synthase to the intracellular citrulline-arginine regeneration pathway. Biochem Pharmacol 69: 97-104, 2005.

82. Yuan L, Wang J and Shen WC: Reversible lipidization prolongs the pharmacological effects, plasma duration and liver retention of octreotide. Pharm Res 22: 220-227, 2005.

83. Zaro JL and Shen WC: Evidence that membrane transduction of oligoarginine does not require vesicle formation. Exp Cell Res 307: 164-173, 2005.

84. Lim CJ and Shen WC: Comparison of Monomeric and Oligomeric Transferrin as Potential Carrier in Oral Delivery of Protein Drugs. J Controlled Release 106: 273-286, 2005. (PMID 15964654).

85. Bai Y, Ann DK and Shen WC: Recombinant granulocyte colony-stimulating factor-transferrin fusion protein as an oral myelopoietic agent. Proc Natl Acad Sci USA 102: 7292-7296, 2005. (PMID 15870205).


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86. Zaro JL and Shen WC: Cytosolic delivery of a p16-peptide oligoarginine conjugate for inhibiting proliferation of MCF7 cells. J Controlled Release 108: 409-417, 2005.

87. Shen LJ, Beloussow K and Shen WC: Modulation of arginine metabolic pathways as the potential anti-tumor mechanism of recombinant arginine deiminase. Cancer Lett 231: 30-35, 2006.

88. Zaro JL, Rajapaksa T, Okamoto CT and Shen WC: Membrane transduction of oligoarginine in HeLa cells is not mediated by macropinocytosis. Mol Pharm 3: 181-186, 2006.

89. Wang J, Hogenkamp DJ, Tran M, Li WY, Yoshimura RF, Johnstone TBC, Compton TR, Nguyen

OT, Parrott JA, Shen WC and Gee KW: Reversible aqueous lipidization of enkephalins yields orally active analgesics. J Drug Targeting 14: 127-136, 2006.

90. Bai Y and Shen WC: Improving the oral efficacy of recombinant granulocyte colony-stimulating factor and transferrin fusion protein by spacer optimization. Pharm Res 23: 2116-2121, 2006. (PMID 16952003).

91. Shen LJ and Shen WC: Drug Evaluation: ADI-PEG-20 – A pegylated arginine deiminase for arginine-auxotrophic cancers. Current Opinion in Mol Therap 8: 240-248, 2006.

92. Bahhady R, Kim KJ, Borok Z, Crandall E and Shen WC: Enhancement of Insulin Transport across Primary Rat Alveolar Epithelial Cell Monolayers by Endogenous Cellular Factor(s). Pharm Res 24: 1713-1719, 2007.

93. Lim CJ, Norouziyan F and Shen WC: Accumulation of Transferrin in Caco-2 Cells: A Possible Mechanism of Intestinal Transferrin Absorption. J Controlled Release 122: 393-398, 2007. (PMID 17586083).

94. Norouziyan F, Shen WC and Hamm-Alvarez S: Rab11 is involved in transferrin trafficking pathways in Caco-2 cells. Am J Physiol 294: C7-C21, 2008. (PMID 17959726).

95. Patel L, Kim KJ, Borok Z, Crandall E, Shen WC and Lee V: Molecular and Functional Expression of Multidrug Resistance-Associated Protein-1 in Primary Cultured Rat Alveolar Epithelial Cells. J Pharm Sci 97: 2340-2349, 2008. (

96. Bahhady R, Kim KJ, Borok Z, Crandall E and Shen WC: Characterization of Protein Factor(s) in Rat Bronchoalveolar Lavage Fluid That Enhance Insulin Transport via Transcytosis across Primary Rat Alveolar Epithelial Cell Monolayers. Eur J Pharm Biopharm 69: 808-816, 2008.

97. Yuan L, Wang J and Shen WC: Lipidization of human interferon-alpha: A new approach toward improving the delivery of protein drugs. J Controlled Release 129: 11-17, 2008.

98. Yuan L, Wang J and Shen WC: Delivery of somatostatin analogues to liver via reversible lipidization. Eur J Pharm Biopharm 70: 615-620, 2008.

99. Amet N, Lee HF and Shen WC: Insertion of the designed helical linker led to increased expression of Tf- based fusion proteins. Pharm Res 26: 523-528, 2009. (PMID 19002568).

100. Barnes M and Shen WC: Disulfide and thioether linked cytochrome c-oligoarginine conjugates in HeLa cells. Int J Pharm 369: 79-84, 2009. (PMID 19059469).


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101. Zaro J, Vekich J, Tran T and Shen WC: Nuclear localization of cell-penetrating peptides is dependent on endocytosis rather than cytosolic delivery. Mol Pharm 6: 337-344, 2009.

102. Patel L, Wang J, Kim KJ, Borok Z, Crandall E and Shen WC: Conjugation with cationic cell-

penetrating peptide increases pulmonary absorption of insulin. Mol Pharm 6: 492-503, 2009.

103. Amet N, Wang W and Shen WC: Human growth hormone–transferrin fusion protein for oral delivery in hypophysectomized rats. J Controlled Release 141: 177-182, 2010. (PMID 19761807).

104. Chen X, Bai Y, Zaro J and Shen WC: Design of an in vivo cleavable disulfide linker in recombinant fusion proteins. BioTechniques 49: 513-518, 2010. (PMID 20615204)

105. Fei L, Ren L, Zaro J and Shen WC: The influence of net charge and charge distribution on cellular uptake and cytosolic localization of arginine-rich peptides. J Drug Targeting 19: 675-680, 2011. (DOI: 10.3109/1061186X.2010.531729), 2011.

106. Chen X, Lee, HF, Zaro J and Shen WC: Effects of Receptor Binding on Plasma Half-life of Bifunctional Transferrin Fusion Proteins. Mol Pharm 8: 457-465, 2011 (PMID 21291358).

107. Wang Y, Chen YS, Zaro JL and Shen WC: Receptor-Mediated Activation of a Proinsulin-Transferrin Fusion Protein in Hepatoma Cells. J Controlled Release 155: 386-392, 2011 (PMID 21756950).

108. Mo R, Zaro J and Shen WC: Comparison of Cationic and Amphipathic Cell Penetrating Peptides for siRNA Delivery and Efficacy. Mol Pharm 9(2): 299-309, 2012 (PMID: 22171592).

109. Mo R, Zaro J, Ou J and Shen WC: Effects of Lipofectamine 2000/siRNA Complexes on Autophagy in Hepatoma Cells. Mol Biotechnol 51: 1-8, 2012 (PMID 22171592).

110. Kenien R, Zaro J and Shen WC: MAP-mediated nuclear delivery of a cargo protein. J Drug Targeting 20: 329-337, 2012 (PMID: 22225540).

111. Zaro J, Fei L and Shen WC: Recombinant peptide constructs for targeted cell penetrating peptide-

mediated delivery. J Controlled Release 158: 357-361, 2012 (PMID: 22326404).

112. Bobst CE, Wang S, Shen WC and Kaltashov IA: Mass spectrometry study of a transferrin-based protein drug reveals the key role of protein aggregation for successful oral delivery. Proc Natl Acad Sci US 109: 13544-13548, 2012 (PMID: 22869744).

113. Kenien R, Shen WC and Zaro JL: Vesicle-to-cytosol transport of disulfide-linked cargo mediated by an amphipathic cell penetrating peptide. J Drug Targeting 20: 793-800, 2012 (PMID: 22994388).

114. Zhang D, Lee HF, Pettit SC, Zaro J, Huang N and Shen WC: Characterization of transferrin receptor-mediated endocytosis and cellular iron delivery of recombinant human serum transferrin from rice (Oryza sativa L.). BMC Biotechnology 12:92, 2012 (DOI: 10.1186/1472-6750-12-92).

115. Wang Y, Shao J, Zaro JL and Shen WC: Proinsulin-transferrin fusion protein as a novel long-acting insulin analog for the inhibition of hepatic glucose production. Diabetes 63: 1779-1788, 2014 (PMID 24353179)


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116. Fei L, Yap LP, Conti PS, Shen WC and Zaro JL: Tumor Targeting of a cell penetrating peptide by fusing with a pH-sensitive histidine-glutamate co-oligopeptide. Biomaterials 35: 4082-4087, 2014 (PMID 24508076).

117. Sun C, Shen WC, Tu J and Zaro JL: Interaction between cell-penetrating peptides and acid-sensitive anionic oligopeptides as a model for the design of targeted drug carriers. Mol Pharm 11(5): 1583-1590, 2014 (PMID 24697211).

118. Yeh TH, Chen YR, Chen SY, Shen WC, Ann DK, Zaro JL and Shen LJ: Selective Intracellular Delivery of Recombinant Arginine Deiminase (ADI) Using pH-Sensitive Cell Penetrating Peptides To Overcome ADI Resistance in Hypoxic Breast Cancer Cells. Mol Pharm, 13(1):262-271, 2016. (PMID: 26642391).

119. Shao J, Zaro JL and Shen WC: Proinsulin−Transferrin Fusion Protein Exhibits a Prolonged and Selective Effect on the Control of Hepatic Glucose Production in an Experimental Model of Type 1 Diabetes. Mol Pharm 13(8): 2641-2646, 2016. (PMID 27280852).

120. Zhou L, Wang HY, Tong S, Okamoto CT, Shen WC and Zaro JL: Single chain Fc-dimer-human growth hormone fusion protein for improved drug delivery. Biomaterials 117: 24-31, 2017.

Reviews and chapters:

121. Shen WC: Radioimmunoassay of nicotinamide nucleotide analogs of nicotine and cotinine. IN: Immunochemical Techniques, Methods in Enzymology, Vol. 84, J.J. Langone and H. Van Vunakis, eds, Academic Press, New York, pp 650-654, 1982.

122. Ryser H J-P and Shen WC: Drug-poly(lysine) conjugates: Their potential for chemotherapy and for the study of endocytosis. IN: Targeting of Drugs with Synthetic Systems, G. Gregoriadis, J. Senior and G. Poste, eds., Plenum Publishing Co., pp 103-121, 1986.

123. Mandel R and Shen WC: Colorimetry. IN: Encyclopedia of Medical Devices and Instrumentation, J.G. Webster, ed., John Wiley & Sons, Vol II, pp 771-779, 1988.

124. Shen WC: Drug-antibody conjugation - chemical aspects of antibody- mediated drug targeting of drug. IN: Proceedings of PharmTech Conference. Aster Publishing Co., Eugene OR, pp 14-23, 1988.

125. Shen WC, Persiani S, Ballou B and Hakala TR: Antibodies as drug carriers for solid tumors. Evaluation of drug-anti-SSEA-1 conjugates in the treatment of teratocarcinoma. IN: Targeted Therapeutic Systems (P. Tyle and B.P. Ram, eds) Marcel Dekker, Inc. pp 289-304, 1989.

126. Shen WC, Wan J and Taub M: Transcellular Transport of protein-polymer conjugates in cultured epithelial cells: The release of a protein from its polymeric carrier during transcytosis. IN: Polymeric Drugs and Drug Delivery Systems, R. L. Dunn and R. Ottenbrite, eds., American Chemical Society, pp 117-127, 1991.

127. Shen WC, Wan J and Ekrami H: Enhancement of polypeptide and protein absorption by macromolecular carriers via endocytosis and transcytosis. Adv Drug Delivery Rev 8:93-113, 1992.


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128. Shen WC and Lin YJ: Basic mechanisms in transepithelium transport enhancement. IN: Drug Permeation Enhancement (DS Hsieh, ed), Marcel Dekker, Inc. pp 25-40, 1994.

129. Shen WC, Shah D, Taub ME and Wan J: Enhancement of transferrin receptor-mediated transcytosis for transepithelial protein delivery. IN: Trends and Future Perspectives in Peptide and Protein Drug Delivery (VHL Lee, M Hashida and Y Mizushima, eds), Harwood Academic Publishers, pp 135-151, 1995.

130. Shen WC: Nuclear import of DNA -- the ultimate targeting in gene therapy, J Drug Targeting 5:11-13, 1997.

131. Shen WC (Guest Editor): Receptor-Mediated Delivery of Macromolecular Drugs. Adv Drug Delivery Rev 29: 195-196, 1998.

132. Shen WC, Wang J and Shen D: Reversible lipidization for the delivery of peptide and protein drugs. IN: Peptide and Protein Drug Delivery (S Frokjaer, L Christrup and P Krogsgaard-Larsen, eds), Munksgaard, Copenhagen, pp 397-410, 1998.

133. Shen WC: Membrane-associated protein thiol-disulfide interchange activity: a potential target for anti-viral and anti-tumor drug design. J Drug Targeting 6: 387-389, 1999.

134. Rozenberg Y, Medvedkin V, Wang J and Shen WC: Alternative Gene Delivery. S.T.P. Pharma Sci 11: 21-30, 2001.

135. Shen WC: Oral peptide and protein delivery: unfulfilled promises? Drug Discovery Today 8: 607-608, 2003.

136. Widera A, Norouziyan F and ShenWC: Mechanisms of TfR-mediated transcytosis and sorting in epithelial cells and applications towards drug delivery. Adv Drug Delivery Rev 55: 1439-1466, 2003.

137. Shen LJ, Mandel R and Shen WC: Colorimetry. IN: Encyclopedia of Medical Devices and Instrumentation (2nd edition), J.G. Webster, ed., John Wiley & Sons, pp. 187-197, 2006.

138. Patel L, Zaro J and Shen WC: Cell Penetrating Peptides: Intracellular Pathways and Pharmaceutical Perspectives. Pharm Res 24: 1977-1992, 2007.

139. Amet N, Chen X, Lee HF, Zaro J and Shen WC: Transferrin receptor-mediated transcytosis for gastrointestinal absorption of protein drugs. In: Targeted Delivery of Small and Macromolecular Drugs (A. Narang and R.I. Mahato, eds) Taylor and Francis, pp. 31-52, 2010.

140. Zaro J, Wang J and Shen WC: Modifying the physiochemical nature of biodrugs by lipidization. In: Biodrug Delivery Systems: Fundamentals, Applications and Clinical Development (M. Morishita and K. Park, eds) Informa Healthcare, N.Y., pp. 309-322, 2010.

141. Chen X, Zaro J and Shen WC: Pharmacokinetics of Recombinant Bifunctional Fusion Proteins. Expert Opinion on Metabolism and Toxicology 8: 581-595, 2012. (PMID: 22418984).


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142. Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8: 445-544, 2012. (PMID: 22966490).

143. Hackett M, Zaro J, Shen WC and Cho MJ: Fatty Acids as Therapeutic Auxiliaries for Oral and Parenteral Formulations. Adv Drug Delivery Rev 65: 1331-1339, 2013. (PMID: 22921839).

144. Chen X, Zaro J and Shen WC: Fusion Protein Linkers: Effects on Production, Bioactivity, and Pharmacokinetics. In: Fusion Protein Technologies for Biopharmaceuticals: Applications and Challenges (Stefan R. Schmidt, ed) Wiley-Blackwell, pp. 57-74, 2013.

145. Chen X, Zaro J and Shen WC: Fusion Protein Linkers: Property, Design and Functionality. Adv Drug Delivery Rev 65: 1357-1369, 2013. (PMID: 23026637).

146. Shen WC: Antibody-Drug Conjugates: A Historical Review. In Antibody-Drug Conjugates: The 21st

Century Magic Bullets for Cancer, (J. Wang, WC Shen & JL Zaro, eds,) Springer, 2015.

147. Zaro JL, Wang J and Shen WC: Summary and Future Directions. In Antibody-Drug Conjugates:

The 21st Century Magic Bullets for Cancer, (J. Wang, WC Shen & J Zaro, eds,) Springer, 2015.

148. Zaro JL and Shen WC: Cationic and amphipathic cell-penetrating peptides (CPPs): Their structures

and in vivo studies in drug delivery. Front Chem Sci Eng 9(4): 407-427, 2015 (DOI 10.1007/s11705-

015-1538-y).

149. Shao J, Zaro JL and Shen WC: Tissue barriers and novel approaches to achieve hepatoselectivity of

subcutaneously-injected insulin therapeutics. Tissue Barriers 4(2): e1156804, 2016.

Textbook:

1. Shen WC and Louie SG: Immunology for Pharmacy Students (Harwood Academic Publishers, Amsterdam, the Netherlands), 1999.

Book Editor:

1. Wang, J, WC Shen and Zaro JL, eds: Antibody-Drug Conjugates: The 21st Century Magic Bullets

for Cancer, (Springer Publishing) 2015.

Meeting Reports

1. Shen WC: Frontiers of Drug Development. IDrugs 2: 1002-1004, 1999.

2. Shen WC: ID Weekly Highlights. Week 36: 35-38, 2001.

3. Shen WC: Controlled Release Society - 29th Annual Meeting and Exposition. IDrugs 5: 908-909, 2002.

http://www.ncbi.nlm.nih.gov/pubmed/22966490

http://www.ncbi.nlm.nih.gov/pubmed/22966490


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Book Review

1. Shen WC: Neocarzinostatin: The past, present, and future of an anticancer drug. J Contr Rel 66: 322, 2000.

Published Abstracts A total of 180 published abstracts in national and international meetings and conferences.

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