一、      个人简介

杨彬，药物化学博士，前诺和诺德美国印第安那波利斯研究中心首席科学家，美国初创生物制药公司马卡迪亚(罗氏)多肽和蛋白质化学主管 (Marcadia Biotech Inc,2011年被Roche罗氏药厂收购）。曾在美国印第安那大学化学系先后担任研究助理教授和副教 授。教育背景方面，本科毕业于现上海海军医科大学药学院，北京军事医学科学院药物所药物化学硕士和博士，并先后在美国伊利诺伊大学香槟分校和美国费城托马斯杰佛逊大学从事博士后研究。研究背景包括药物化学，多肽和蛋白质药物化学，药物合成设计，及分子生物学等的生物化学领域。从事过的研究领域涉及抗肿瘤药物，抗HIV抗病毒药物，和抗糖尿病，肥胖和肝脂肪代谢性药物等。 在著名期刊如自然杂志（Nature）,自然医学（ Nature medicine）, 美国生物化学杂志(JBC)，美国药物化学杂志（J Med Chem）和分子代谢（Molucular Metabolism）等以第一作者和主要贡献者发表多篇高引用研究论文。

在新药研发领域的特殊贡献是最早研究发现多功能Incretin类似物,而且是首次报道GLP-1/GIP/GCG三功能多肽药物的化学家(Nature Medicine,2015, 21, 27–36)。此多功能Incretin多肽类抗糖尿病药物的发现直接推动了2个 first-in-class 1.1类新药MAR709/RG7697/NN2746 & MAR423/NN1706 进入临床研究，并引领了不同著名医药公司相继研发了多个此类新型多肽药物在抗糖尿病，抗肥胖症和脂代谢领域的临床研究，其中礼来的GLP-1/GIP双功能 Tizepatide(替尓泊肽) 首先在2022年获得美国FDA批准用于II型糖尿病，和其三功能药物 Retatrutide 在临床上都表现出比GLP-1单一药物 Semeglutide（司美格鲁肽）更强的减肥效果。另外，在托马斯杰佛逊大学博士后研究期间合成筛选的抗HIV 新型多肽专利曾被位于美国纽约州的生物技术公司Oyagen购买合作开发。

在多肽蛋白质药物化学研发方面有深厚的专业背景，并在前礼来主管生物药的研发总裁，世界上第一款餐前快速胰岛素（Humalog，礼来优泌乐）的发明者Richard DiMarchi博士的直接领导下工作多年,积累了新药研发的实际经验。有意在未来的职业发展中，继续在多肽和蛋白质药物，小核酸多肽偶联物和抗体偶联药物方面研发新产品。

二、      教育及工作经历

工作经历

07/2023 - 至今：研究员(特聘)，浙工大德清莫干山研究院，浙江德清

07/2021– 05/2023: Principal Scientist Novo Nordisk Research Center Indianapolis, Indianapolis, Indiana  诺和诺德美国印第安纳波利斯研发中心， 首席科学家

02/2016 – 06/2021: Senior Research Scientist Novo Nordisk Research Center Indianapolis, Indianapolis, Indiana  诺和诺德美国印第安纳波利斯研发中心， 资深科学家

01/2012 - 01/2016：Associate Scientist/Research Professor (Non-tenure track faculty) Indiana University, Department of Chemistry, Bloomington, Indiana, USA 美国印第安纳大学布卢明顿分校化学系研究副教授 （正式教职）

08/2008 - 12/2011: Director of Peptide Chemistry Marcadia Biotech Inc (Roche), Carmel, Indiana, USA (Roche, 2011 acquired) 美国马卡迪亚 (罗氏)生物公司， 多肽化学主任

06/2004 - 08/2008: Assistant Scientist (Non-tenure track faculty) Indiana University, Department of Chemistry, Bloomington, Indiana, USA 美国印第安纳大学布卢明顿分校化学系助理研究员/研究助理教授 （正式教职）

10/2000 - 04/2001: Postdoctoral Research Associate  University of Illinois at Urbana–Champaign, Department of Biochemistry, Urbana, IL, USA 美国伊利诺伊大学香槟分校博士后研究助理

01/2000 - 05/2004: Postdoctoral Research Associate Thomas Jefferson University, Department of Medicine, Philadelphia, PA, USA  美国费城托马斯杰佛逊大学博士后研究助理

08/1996 - 12/1999: 助理研究员，北京军事医学科学院药物所

教育经历

药物化学，博士，08/1993 - 07/1996 军事医学科学院药物所， 北京

药物化学，硕士，08/1990 - 07/1993 军事医学科学院药物所， 北京

药学      学士, 08/1984 - 07/1988 第二军医大学药学系，上海

三、      个人荣誉与获奖

Excellent honor graduate student of Academic of Military Medical Science

New drug approval award from Academic of Military Medical Science

Patent license-out award from Thomas Jefferson University

Entrepreneurship recognizes and scientific awards from Indiana University

Milestone awards from Novo Nordisk

四、      承担的主要科研项目

Multiple function incretin hormones initiate the novel anti-diabetes and obesity drug developments: Structure-activity relationships study and analogues design and synthesis of the gut and incretin hormones including Glucagon, GLP-1, GIP, Calcitonin, Insulin and Amylin over the last 20 years. One of the main contribution chemists in developing and concepting the dual GLP-1/glucagon and GLP-1/GIP co-agonists. The primary chemist to develop and report the GLP-1/GIP/glucagon incretin tri-agonists, and also the first chemist who reports GIP peptide antagonists that successfully mimetics the GIPR antibody function in vivo. These novel multi-acting incretin peptides which some of on clinical trials by big pharma of Merck, Roche and Novo Nordisk have demonstrated the potential better effective therapeutics in the managements of obesity and diabetes than the marketing mono-GLP-1 agonist drugs.

Nuclear hormones tissue targeting delivery: Nuclear hormones e.g. estrogen, thyroid hormones and corticosteroids play important roles in insulin regulatory and glucose homeostasis. Through conjugating with peptides e.g. GLP-1, glucagon, insulin or FGF21, to specifically deliver such nuclear hormone

.molecules to pancreas, liver or adipocytes to avoid other tissue’s side effects. Development of special conjugation linkers that ensure to release the nuclear hormone molecules intracellularly while keep the conjugates stable in circulations.

Peptide HIV vif protein inhibitors and mechanisms study of APOBEC3G/CEM15: Phage display screen of peptide library that binding to protein vif inhibiting vif dimerization which responsible for HIV virial replications. Fist disclosure the deamination-edited mechanism of anti-HIV virus protein APOBEC3G, developing method analysis G-to-A/C-to-U HIV DNA mutation induced by APOBEC3G. APOBEC3G cellar associated proteins separation and determination by proteomics analysis methods.

Expertise in design and modification of peptide and protein to improve longer PK in drug developments: Experienced in acylation, pegylation and large molecules e.g. albumin and Fc covalent linkage modifications. Developments conjugation linkers be able to tunable, releasable or tissue metastable/labile. Experienced in small molecular and peptide & protein prodrugs design.

五、      教学情况

1993 – 1999: Teaching advanced medicinal chemistry and organic chemistry for graduates at Academic of Military Medical Science, Beijing, China.

2005 - 2016: Co-mentors of three PhD students in chemistry and biochemistry at Indiana University.

六、      论文、专著与专利

·         www.researcherid.com Web of Science Researcher ID W-7014-2019

·         ORCID: 0000-0003-1180-6184

·         The citation numbers are from current (Feb 2023) google scholar

1.  Arkadiusz Liskiewicz, Ahmed Khalil, Daniela Liskiewicz, Aaron Novikoff, Gerald Grandl, Gandhari Maity- Kumar, Robert M. Gutgesell, Mostafa Bakhti, Aimée Bastidas-Ponce, Oliver Czarnecki, Konstantinos Makris, Heiko Lickert, Annette Feuchtinger, Monica Tost, Callum Coupland, Lisa Ständer, Seun Akindehin, Sneha Prakash, Faiyaz Abrar, Russell L. Castelino, Yantao He, Patrick J. Knerr, Bin Yang, Wouter F. J. Hogendorf, Shiqi Zhang, Susanna M. Hofmann, Brian Finan, Richard D. DiMarchi, Matthias H. Tschöp, Jonathan D. Douros & Timo D. Müller. Glucose-dependent insulinotropic polypeptide regulates body weight and food intake via GABAergic neurons in mice. Nature Metabolism 5, 2075–2085 (2023).

2.  Kimberley El, Jonathan D. Douros, Francis S. Willard, Aaron Novikoff, Ashot Sargsyan, Diego Perez-Tilve, David B. Wainscott, Bin Yang, Alex Chen, Donald Wothe, Callum Coupland, Mattias H. Tschöp, Brian Finan, David A. D’Alessio, Kyle W. Sloop, Timo D. Müller & Jonathan E. Campbell. The incretin co-agonist tirzepatide requires GIPR for hormone secretion from human islets. Nature Metabolism 5, 945–954 (2023).

3.  Bin Yang, Vasily M. Gelfanov, Kimberley El, Alex Chen, Rebecca Rohlfs, Barent DuBois, Ann Maria Kruse Hansen, Diego Perez-Tilve, Patrick J. Knerr, David D'Alessio, Jonathan E. Campbell, Jonathan D. Douros, Brian Finan. Discovery of a potent GIPR peptide antagonist that is effective in rodent and human systems. Molecular Metabolism, 2022, Dec, Volume 66: 101638 （Cited 12 till Feb 2024

4.  Taylor Fuselier, Paula Mota de Sa, M.M. Fahd Qadir, Beibei Xu, Camille Allard, Mathew M.Meyers, Joseph P.Tiano, Bin Yang Vasily Gelfanov, Sarah H.Lindsey, Richard D. Dimarchi, FranckMauvais-Jarvis. Efficacy of glucagon-like peptide-1 and estrogen dual agonist in pancreatic islets protection and pre-clinical models of insulin-deficient diabetes. Cell Reports Medicine, 2022, 3(4):100598. Cited 2 (citation on google scholar)

5.  Quarta C, Stemmer K, Novikoff A, Yang B, Klingelhuber F,  Harger A,  Bakhti M,  Bastidas-Ponce A,  Bauge E, Clemmensen C, Colldén G, Cota P, Drucker D, García-Cáceres C, Grandl G, Hennuyer N,  Herzig S, Hofmann S, Kulaj K, Lalloyer F, Lickert H, Maity G,  Perez-Tilve D,  Sanchez-Garrido MA,  Zhang Q,  Staels B, Krahmer N,  DiMarchi R,  Tschoep M,  Finan B,  Müller T. GLP-1-mediated delivery of tesaglitazar improves obesity and glucose metabolism in male mice. Nature Metabolism, 2022, 4: 1071-1088. Cited 3

6.  Bin Yang*, Vasily M. Gelfanov, Diego Perez-Tilve, Barent DuBois, Rebecca Rohlfs, Jay Levy, Jonathan D. Douros, Brian Finan, John P. Mayer, and Richard D. DiMarchi. Optimization of Glucagon Truncated Peptides to Achieve Selective, High Potency, Full Antagonists. Journal of Medicinal Chemistry, 2021, 64, 4697 – 4708. Cited 8

7.  Brian Finan, Sebastian D. Parlee, Bin Yang. Nuclear hormone and peptide hormone therapeutics for NAFLD and NASH, Molecular Metabolism, Volume 46, 2021, 101153, ISSN 2212-8778 (invited review). Cited 6

8.  Sachs, S, Bastidas-Ponce, A, Tritschler, S, …., Yang B............. et al. Targeted pharmacological therapy restores β-

cell function for diabetes remission. Nat Metab 2, 192–209 (2020). Cited 53

9.  Décarie-Spain L, Fisette A, Zhu Z, Yang B, DiMarchi RD, Tschöp MH, Finan B, Fulton S, Clemmensen C. “GLP-1/dexamethasone inhibits food reward without inducing mood and memory deficits in mice.” Neuropharmacology. 2019 Apr 1;151:55-63. Cited 8

10.  Mroz PA, Finan B, Gelfanov V, Yang B, Tschöp MH, DiMarchi RD, Perez-Tilve D. “Optimized GIP analogs promote body weight lowering in mice through GIPR agonism not antagonism. Mol Metab. 2019 Feb;20:51-

62. Cited 43

11.  Quarta C, Clemmensen C, Zhu Z, Yang B, …., DiMarchi RD, Finan B, Tschöp MH. “Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity. Cell Metab. 2017 Oct 3;26(4):620-632. Cited 35

12.  Finan B, Clemmensen C, Zhu Z, …., Yang B, Tschöp MH, DiMarchi R, Müller TD. “Chemical Hybridization of Glucagon and Thyroid Hormone Optimizes Therapeutic Impact for Metabolic Disease. Cell. 2016 Oct 20;167(3):843-857. Cited 159

13.  Tiano JP, Tate CR, Yang BS, DiMarchi R, Mauvais-Jarvis F. “Effect of targeted estrogen delivery using glucagon-like peptide-1 on insulin secretion, insulin sensitivity and glucose homeostasis”. Sci Rep. 2015 May 13;5:10211. doi: 10.1038/srep10211. Cited 23

14.  Xu, Pingwen; Cao, Xuehong; et al.; Yang, Bin;  DiMarchi, Richard; et al.; Xu, Yong. “Estrogen receptor-alpha in medial amygdala neurons regulates body weight”. J Clin Invest. 2015 Jul 1;125(7):2861-76. Cited 49

15.  Cao, Xuehong; Xu, Pingwen; et al., Yang, Bin; DiMarchi, Richard; et al.; Xu, Yong. “Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice”. J Clin Invest. 2014 Oct;124(10):4351-62. Cited 59

16.  Brian Finan*(co-first author, biology), Bin Yang*(co-first author, chemistry), Nickki Ottaway, Diego Perez- Tilve, …, Lianshan Zhang, …, Richard D. DiMarchi & Matthias H. Tschöp. “A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents”. Nature Medicine, 21, 27–36 (2015) doi:10.1038/nm.3761. Cited 509 (共同第一作者，化学第一作者)

17.  Finan, B.; Ma, T.; Ottaway, N.; Muller, T. D.; Habegger, K. M.; Heppner, K. M.; Kirchner, H.; Holland, J.; Hembree, J.; Raver, C.; Lockie, S. H.; Smiley, D. L.; Gelfanov, V.; Yang, B.; Lianshan Zhang; …; DiMarchi,

R. D.; Tschop, M. H. “Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans”. Sci Transl Med 2013, 5(209):209ra151. doi: 10.1126/scitranslmed.3007218. Cited 455

18.  Finan B, Bin Yang, Ottaway N, Kerstin Stemmer, Timo D Müller, …, Richard D DiMarchi & Matthias H Tschöp. “Targeted estrogen delivery reverses the metabolic syndrome”. Nature Medicine. 2012, 18(12): 1847-1856. Cited 265

19.  Jialing Huang, Zhihui Liang, Bin Yang, Heng Tian, Jin Ma, and Hui Zhang. “Derepression of microRNA- mediated protein translation inhibition by apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G) and its family members.” Journal of Biological Chemistry, 2007, 282(46):33632-40. Cited 96

20.  Bin Yang, Keyang Chen, Chune Zhang, Sophia Huang and Hui Zhang. “Virion-associated Uracil DNA Glycosylase-2 and Apurinic/Apyrimidinic Endonuclease Are Involved in the Degradation of APOBEC3G- edited Nascent HIV-1 DNA” Journal of Biological Chemistry, 2007, 282(16): 11667-75. Cited 169

21.  Bin Yang; Gelfanov, V. M.; DiMarchi, R. D. “Synthesis and Biological Assessment of Sulfonic Acid-Based Glucagon Antagonists”. In Understanding Biology Using Peptides, Proceedings of the 19th American Peptide Symposium. Springer Publishing Co: New York, 2005; p 305-306.

22.  Bin Yang; DiMarchi, R. D. “A Novel Approach to Resin-based Cysteine Alkylation”. In Understanding Biology Using Peptides, Proceedings of the 19th American Peptide Symposium. Springer Publishing Co: New York, 2005; p 88-89.

23.  Dongxiang Liu, Bin Yang, Rong Cao and Ziwei Huang. “A chemical strategy to promote helical peptide- protein interactions involved in apoptosis.” Bioorganic & Medicinal Chemistry Letters, 2005, 15(20):4467-9. Cited 7

24.  Bin Yang, Dongxiang Liu and Ziwei Huang. “Synthesis and helical structure of lactam-bridged BH3 peptides derived from pro-apoptotic Bcl-2 family proteins.” Bioorganic & Medicinal Chemistry Letters, 2004, 14(6): 1403-06. Cited 57

25.  Jianhua Fang, Satoshi Kubota, Bin Yang, Naiming Zhou, Hui Zhang, Roseline Godbout and Roger J. Pomerantz. “A DEAD box protein facilitates HIV-1 replication as a cellular co-factor of Rev.” Virology. 2004, 330(2):471-80. Cited 124

26.  Hui Zhang*, Bin Yang, Roger J. Pomerantz, Chune Zhang, Shyamala C. Arunachalam, and Ling Gao. “The Cytidine Deaminase CEM15 Induces Hypermutation in Newly Synthesized HIV-1 DNA.” Nature, 2003, 424(6944): 94-98. (Hui Zhang was PI, Bin Yang was the main contributor). Cited 1306

27.  Bin Yang, Ling Gao, Lin Li, Zhixian Lu, Xuejun Fan, Charvi A. Patel, Roger J. Pomerantz, Garrett C. DuBois, and Hui Zhang. “Potent Suppression of Viral Infectivity by Peptides that Inhibit Multimerization of Human Immunodeficiency Virus Type I (HIV-1) Vif Proteins.” Journal of Biological Chemistry, 2003, 278(8): 6596- 6602. Cited 100

28.  Bin Yang, Zhenkai Ding, Zongjin Han and Qikai Zhang. “Synthesis of salmon calcitonin analogues using Fmoc-based chemistry on MBHA resin.” Chinese Chemical Letters, 1999, 10(7): 549-552.

30.    杨彬，蔡耘，丁振闿, 等。鲑鱼降钙素类似物在水溶液中的化学稳定性研究。药学学报: 1998, 33(8): 610-615.   

31.    杨彬，董华进，丁振闿, 等。鲑鱼降钙素类似物[Glu31,Pro32-N(C2H5)2]sCT 的合成，二级结构及活性研究。军事医学科学院院刊: 1997, 21(4): 247-250

32.    杨彬，恽榴红，等。五碳环并苯二氮卓类三环化合物的合成及其选择性 M1 受体拮抗作用。  中国药物化学杂志：1997, 7(2): 79-83

33.    杨彬，恽榴红。新的苯并二氮卓类三环化合物：1H,10H-4,9-二氢-环戊并[1,2-b][1,5] 苯并二氮卓- 10-酮及其 3-甲基衍生物的合成。合成化学：1996, 4(2): 164-167

中文综述 （在国内学习工作期间发表）

1.  杨彬，丁振闿。T 肽研究进展。国外医学-药学分册: 1994, 21(6): 336-339

2.    杨彬，丁振闿。降钙素的构效关系研究进展。中国药物化学杂志: 1995, 30(11): 643-646

3.    杨彬，丁振闿。抗哮喘药物的研究进展。国外医学-药学分册: 1998, 25(2): 76-82

4.    杨彬，恽榴红。治疗早老性痴呆药物的研究现状及前景。中国药物化学杂志: 1998, 33(7): 393-396

5.    杨彬，恽榴红。肿瘤多药耐药蛋白抑制剂。军事医学科学院院刊: 1999, 23(1): 67-71

6.    杨彬，丁振闿。半胱氨酸组织蛋白酶抑制剂：一类新型的骨质疏松治疗药物。国外医学-药学分册: 2000, 27(2): 79-84

专利

·            Bin Yang and Brian Finan. Long-acting GIP peptide antagonists. (2022 January filed, PCT)

·            Richard DiMarchi and Bin Yang. Insulin Nuclear Hormone Conjugates. WO2017210242A1

·            Richard DiMarchi, Brian Finan, Bin Yang and Zhimeng Zhu. Glucagon T3 Conjugates. WO2017210099A1

·            Richard DiMarchi and Bin Yang. Glucagon superfamily peptides exhibiting glucocorticoid receptor activity. US8859491

·            Richard DiMarchi, David L. Smiley and Bin S. Yang. Glucagon/GLP-1 receptor co-agonists. US 9309301, 8729017

·            Richard DiMarchi, Bin Yang and Brian Finan. Glucagon Superfamily Peptides Exhibiting Nuclear Hormone Receptor Activity. US 9127088

·            Richard DiMarchi, Bin Yang and Chenguang Ouyang. “Compounds Exhibiting Glucagon Antagonist and GLP-1 Agonist”. US8980830

·            Richard DiMarchi and Bin Yang. “Glucagon Antagonists”. US8981047

·            Hui Zhang, Roger J. Pomerantz, Bin Yang. “Multimerization of HIV-1 Vif Protein as a Therapeutic Target.” US2008/0167199. (Licensed by start-up biotech OyaGen: www.oyageninc.com).

·            Bin Yang, Zhenkai Ding, Zongjin Han, Huajin Dong, Bihai Li, Xiuying Ma. “Preparation of eel and salmon calcitonin analogs which do not contain disulfide bond.” Faming Zhuanli Shenqing Gongkai Shuomingshu

(Chinese Patent, 1997), 10 pp. CODEN: CNXXEV CN 1167114 A 19971210 CAN 132:50248 AN

2000:22011