一、      個人簡介

楊彬，藥物化學(xué)博士，前諾和諾德美國印第安那波利斯研究中心首席科學(xué)家，美國初創(chuàng)生物制藥公司馬卡迪亞(羅氏)多肽和蛋白質(zhì)化學(xué)主管 (Marcadia Biotech Inc,2011年被Roche羅氏藥廠收購）。曾在美國印第安那大學(xué)化學(xué)系先后擔(dān)任研究助理教授和副教 授。教育背景方面，本科畢業(yè)于現(xiàn)上海海軍醫(yī)科大學(xué)藥學(xué)院，北京軍事醫(yī)學(xué)科學(xué)院藥物所藥物化學(xué)碩士和博士，并先后在美國伊利諾伊大學(xué)香檳分校和美國費城托馬斯杰佛遜大學(xué)從事博士后研究。研究背景包括藥物化學(xué)，多肽和蛋白質(zhì)藥物化學(xué)，藥物合成設(shè)計，及分子生物學(xué)等的生物化學(xué)領(lǐng)域。從事過的研究領(lǐng)域涉及抗腫瘤藥物，抗HIV抗病毒藥物，和抗糖尿病，肥胖和肝脂肪代謝性藥物等。 在著名期刊如自然雜志（Nature）,自然醫(yī)學(xué)（ Nature medicine）, 美國生物化學(xué)雜志(JBC)，美國藥物化學(xué)雜志（J Med Chem）和分子代謝（Molucular Metabolism）等以第一作者和主要貢獻者發(fā)表多篇高引用研究論文。

在新藥研發(fā)領(lǐng)域的特殊貢獻是最早研究發(fā)現(xiàn)多功能Incretin類似物,而且是首次報道GLP-1/GIP/GCG三功能多肽藥物的化學(xué)家(Nature Medicine,2015, 21, 27–36)。此多功能Incretin多肽類抗糖尿病藥物的發(fā)現(xiàn)直接推動了2個 first-in-class 1.1類新藥MAR709/RG7697/NN2746 & MAR423/NN1706 進入臨床研究，并引領(lǐng)了不同著名醫(yī)藥公司相繼研發(fā)了多個此類新型多肽藥物在抗糖尿病，抗肥胖癥和脂代謝領(lǐng)域的臨床研究，其中禮來的GLP-1/GIP雙功能 Tizepatide(替尓泊肽) 首先在2022年獲得美國FDA批準(zhǔn)用于II型糖尿病，和其三功能藥物 Retatrutide 在臨床上都表現(xiàn)出比GLP-1單一藥物 Semeglutide（司美格魯肽）更強的減肥效果。另外，在托馬斯杰佛遜大學(xué)博士后研究期間合成篩選的抗HIV 新型多肽專利曾被位于美國紐約州的生物技術(shù)公司Oyagen購買合作開發(fā)。

在多肽蛋白質(zhì)藥物化學(xué)研發(fā)方面有深厚的專業(yè)背景，并在前禮來主管生物藥的研發(fā)總裁，世界上第一款餐前快速胰島素（Humalog，禮來優(yōu)泌樂）的發(fā)明者Richard DiMarchi博士的直接領(lǐng)導(dǎo)下工作多年,積累了新藥研發(fā)的實際經(jīng)驗。有意在未來的職業(yè)發(fā)展中，繼續(xù)在多肽和蛋白質(zhì)藥物，小核酸多肽偶聯(lián)物和抗體偶聯(lián)藥物方面研發(fā)新產(chǎn)品。

二、      教育及工作經(jīng)歷

工作經(jīng)歷

07/2023 - 至今：     研究員(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

                        諾和諾德美國印第安納波利斯研發(fā)中心， 首席科學(xué)家

   02/2016 – 06/2021:  Senior Research Scientist Novo Nordisk Research Center Indianapolis, Indianapolis, Indiana  

                        諾和諾德美國印第安納波利斯研發(fā)中心， 資深科學(xué)家

   01/2012 - 01/2016：  Associate Scientist/Research Professor (Non-tenure track faculty) Indiana University, 

                        Department of Chemistry, Bloomington, Indiana, USA 美國印第安納大學(xué)布盧明頓分校化學(xué)系研究副教授 

   08/2008 - 12/2011:   Director of Peptide Chemistry Marcadia Biotech Inc (Roche), Carmel, Indiana, USA 

                        (Roche, 2011 acquired) 美國馬卡迪亞 (羅氏)生物公司， 多肽化學(xué)主任

   06/2004 - 08/2008:   Assistant Scientist (Non-tenure track faculty) Indiana University, Department of Chemistry, 

                        Bloomington, Indiana, USA 美國印第安納大學(xué)布盧明頓分校化學(xué)系助理研究員/研究助理教授 （正式教職）

   10/2000 - 04/2001:   Postdoctoral Research Associate  University of Illinois at Urbana–Champaign, 

                        Department of Biochemistry, Urbana, IL, USA 美國伊利諾伊大學(xué)香檳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  美國費城托馬斯杰佛遜大學(xué)博士后研究助理

08/1996 - 12/1999:   助理研究員，北京軍事醫(yī)學(xué)科學(xué)院藥物所

教育經(jīng)歷

08/1993 - 07/1996    軍事醫(yī)學(xué)科學(xué)院藥物所，藥物化學(xué)，博士，北京

08/1990 - 07/1993    軍事醫(yī)學(xué)科學(xué)院藥物所，藥物化學(xué)，碩士，北京

08/1984 - 07/1988    第二軍醫(yī)大學(xué)藥學(xué)系，  藥學(xué)，    學(xué)士, 上海

三、      個人榮譽與獲獎

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、      承擔(dān)的主要科研項目

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、      教學(xué)情況

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、      論文、專著與專利

·      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 St?nder, 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. Tsch?p, 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. Tsch?p, 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, Tsch?p 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, Tsch?p 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, Tsch?p 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, Tsch?p 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. Tsch?p. “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，化學(xué)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 Tsch?p. “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.

29.  Bin Yang, Houli Jiang, Zhenkai Ding and Qikai Zhang. “Secondary structure in solution of an analogue of salmon calcitonin: [Val1, Ala7]sCT.” Chinese Chemical Letters, 1999, 10(7): 555-558.

 30.  楊彬，蔡耘，丁振闿等。鮭魚降鈣素類似物在水溶液中的化學(xué)穩(wěn)定性研究。藥學(xué)學(xué)報: 1998, 33(8): 610-615.   

 31.楊彬，董華進，丁振闿等。鮭魚降鈣素類似物[Glu31,Pro32-N(C2H5)2]sCT 的合成，二級結(jié)構(gòu)及活性研究。軍事醫(yī)學(xué)科學(xué)院院刊:1997, 21(4): 247-250

 32.  楊彬，惲榴紅等。五碳環(huán)并苯二氮卓類三環(huán)化合物的合成及其選擇性 M1 受體拮抗作用。  中國藥物化學(xué)雜志：1997, 7(2): 79-83

 33.楊彬，惲榴紅。新的苯并二氮卓類三環(huán)化合物：1H,10H-4,9-二氫-環(huán)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。合成化學(xué)：1996, 4(2): 164-167

中文綜述 （在國內(nèi)學(xué)習(xí)工作期間發(fā)表）

   1. 楊彬，丁振闿。T 肽研究進展。國外醫(yī)學(xué)-藥學(xué)分冊: 1994, 21(6): 336-339

              2.    楊彬，丁振闿。降鈣素的構(gòu)效關(guān)系研究進展。中國藥物化學(xué)雜志: 1995, 30(11): 643-646

              3.    楊彬，丁振闿。抗哮喘藥物的研究進展。國外醫(yī)學(xué)-藥學(xué)分冊: 1998, 25(2): 76-82

              4.   楊彬，惲榴紅。治療早老性癡呆藥物的研究現(xiàn)狀及前景。中國藥物化學(xué)雜志: 1998, 33(7): 393-396

              5.    楊彬，惲榴紅。腫瘤多藥耐藥蛋白抑制劑。軍事醫(yī)學(xué)科學(xué)院院刊: 1999, 23(1): 67-71

              6.    楊彬，丁振闿。半胱氨酸組織蛋白酶抑制劑：一類新型的骨質(zhì)疏松治療藥物。國外醫(yī)學(xué)-藥學(xué)分冊: 2000, 27(2): 79-84 

專利

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

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

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

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

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

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

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

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

9.      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: 

10.   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.”