Raymond C. Stevens

Raymond C. Stevens (born 1963) is an American chemist and structural biologist, Founder, CEO and Board Member of Structure Therapeutics;[2] Founding Director of the iHuman Institute at ShanghaiTech University; Professor Emeritus of Chemistry, and Founding Director of the Bridge Institute at the University of Southern California; Board Member, Danaher Corporation.[3]

Raymond C. Stevens
Born1963
NationalityAmerican
Alma materUniversity of Southern Maine, University of Southern California
AwardsBeckman Young Investigators Award,[1]
Scientific career
FieldsStructural biology
InstitutionsShanghaiTech University, University of Southern California

Biography

Stevens was born into a military family. In 1969 his father died in the Air Force, and his mother took several part-time jobs to support the family. He was raised in Auburn, Maine.

In 1980, Stevens joined the Army under their split option training program and conducted basic training at Fort Dix, New Jersey and advanced individual training at Fort Sam Houston, Texas. While engaged in his military service, Stevens entered the University of Southern Maine in the Computer Science program in 1981. However, an enthusiastic professor (John Ricci) converted him to the study of Chemistry. He spent two summers working as an intern at the Brookhaven National Laboratory in Long Island with Professor Ricci, and Drs. Thomas Koetzle and Dick McMullan, where he first learned how to determine the molecular structure of compounds by X-ray and neutron diffraction. While there he also met a University of Southern California research team led by Dr. Robert Bau; after he obtained a Bachelor of Science degree in chemistry at USM, he entered the University of Southern California in pursuit of a Doctor of Philosophy degree in Chemistry working with Professor Robert Bau and Nobel Laureate Professor, George Olah. He completed his Ph.D. in 26 months, graduating in 1988.[4]

Although science is a major part of his life, Stevens climbs mountains with his wife and children and runs ultramarathons including the Vermont 100 Mile Endurance Run[5] and American River 50 Mile Endurance Run,[6] and in 2011 he successfully completed the 156 mile Marathon des Sables[7] across the Moroccan Sahara Desert. Currently working on climbing the 7 highest mountains on the 7 continents, he has climbed Mt. Kilimanjaro, Mt. Elbrus, Aconcagua, Vinson Massif and Mt. Kosciuszko. Next mountains are Mt. Everest and Denali.

Scientific career

After obtaining his Ph.D., Stevens accepted a postdoctoral position in 1988 in the lab of Nobel Laureate William N. Lipscomb, Jr. in the chemistry department at Harvard University where he focused on the large allosteric enzyme aspartate carbamoyltransferase.[8][9][10][11][12][13][14][15][16] In 1991, he accepted a tenure-track position at the University of California, Berkeley in the chemistry department with a joint appointment in neurobiology. His initial research as an assistant professor focused on structural neurobiology and immunology, combining chemistry, structural biology and protein chemistry with a specific biological interest in understanding how the G protein-coupled receptor (GPCR) superfamily works. A seminal collaboration for Stevens was with Professor Peter G. Schultz where they jointly published a series of Science and Nature papers describing the immunological evolution of antibodies through careful structural studies.[17][18][19][20] In 1999, Stevens left Berkeley to take a tenured position at The Scripps Research Institute. While at The Scripps Research Institute, Stevens has helped to found and establish the Joint Center for Structural Genomics,[21] Joint Center for Innovative Membrane Protein Technologies,[22] and the GPCR Network,[23] all funded by the National Institutes of Health with direct guidance from NIGMS. In 2012, Stevens co-founded the iHuman Institute at ShanghaiTech University.[24] In 2014, Stevens moved his lab from The Scripps Research Institute to the University of Southern California, where he is currently the Provost Professor of Biological Sciences and Chemistry and he founded the Bridge Institute to converge the arts and sciences.[25]

Stevens is known for obtaining the structures of many biologically significant proteins and his technological innovations. He is considered a pioneer of high-throughput x-ray crystallography and structural genomics.[26] His laboratory has led to the contribution of over 500 protein structure entries in the Protein Data Bank www.pdb.org. Stevens has withdrawn two different structures of ligand-bound clostridial neurotoxins.[27][28]

In October 2007, Stevens and colleagues published the first high-resolution structure of a human GPCR.[29][30] The β2-adrenergic receptor work was quickly followed up 9 months later by the determination of the structure of the human A2A adenosine receptor structure,[31] also known as the caffeine receptor. In 2010, the structures of the human chemokine CXCR4 receptor (HIV co-receptor),[32] the human dopamine D3 receptor[33] and the human Histamine H1 receptor[34] were published. In addition to these inactive-state structures, Stevens and colleagues solved the structure of an agonist-bound A2A adenosine receptor.[35]

Subsequent novel human receptor structures include:

2012: The first structure of a lipid-activated GPCR, the sphingolipid,[36] the human kappa-opioid receptor[37] and the human nociceptin/orphanin FQ peptide receptor.[38]

2013: Serotonin receptors 5-HT1B and 5-HT2B,[39][40] the second HIV co-receptor, C-C chemokine receptor type 5 (CCR5) [41] and the first structure of a non-class A GPCR, the transmembrane domain of the human Metabotropic glutamate receptor 1 (mGluR1) [42] and the first structures of non-rhodopsin family GPCRs, the transmembrane domain of the human Smoothened receptor from the Frizzled/Taste2 family [40] and the transmembrane domain of the human glucagon receptor (GCGR) from the adhesion (class B) family.

2014: The human P2Y receptor 12 (P2Y12) bound to antagonist or agonist;[43][44] the human Delta opioid receptor at 1.8A [45] and the first structure of a class C GPCR, the transmembrane domain of the human Metabotropic glutamate receptor 1 (mGluR1).[42]

2015: The human Lysophosphatidic acid receptor 1 (LPAR1),[46] the human angiotensin II receptor type 1 (AT1R),[47] human P2Y receptor 1 (P2Y1);[48] and the human Rhodopsin-Arrestin complex.[49]

2016: The marijuana receptor—human Cannabinoid receptor type 1 (CB1) [50] and the human C-C chemokine receptor type 2 (CCR2) [51]

2017:The human apelin receptor [52] and the human angiotensin II receptor 2 (AT2R) [53] as well as the full length human glucagon receptor (GPCR)[54] and trans membrane domain of the human glucagon like peptide receptor 1 (GLP1R) [55]

2018: The human seratonin receptor 5HT2C [56] human neuropeptide Y Y1 receptor [57] platelet activating factor receptor [58] and the trans membrane domain of the human frizzled 4 receptor [59]

2019: The human prostaglandin E2 receptor3 (EP3),[60] the human cannabinoid receptor CB2,[61] the human neurokinin 1 receptor,[62] and the melatonin receptors MT1 [63] and MT2 [64]

2020:The human melanocortin 4 receptor (MC4),[65][66][67]

In combination with the structural studies, working with the computational biology community to conduct GPCR Dock 2008[68] and GPCR Dock 2010[69] has helped to evaluate where the field is at, and functional studies using HDX[70] and NMR are conducted by Stevens and collaborators to understand how the receptors work at the molecular level, and what fundamental and basic insights can be gained towards developing therapeutic drugs.

Structure based drug discovery

In 1992, Stevens worked with researchers at Gilead on the structural studies of neuraminidase inhibitors that eventually became Tamiflu,[71][72][73] and later partnered with Roche. After the initial experience with structure based drug discovery from 1992 to 1997 with Gilead and Tamiflu, Stevens focused on understanding the basic mechanism of how Botox (botulinum toxin) works, and on ways to use this scaffold for next generation protein therapeutics. In parallel to the work on botulinum toxin, he worked on the enzymes involved in the catecholamine biosynthetic pathway, specifically the three aromatic amino acid hydroxylases including phenylalanine hydroxylase. From 1999 to 2004, Stevens was involved in the startup of Syrrx that developed the marketed drug Nesina for type II diabetes. From 2000 to 2010, Stevens has worked with BioMarin Pharmaceutical to develop Kuvan (tetrahydrobiopterin) and assisted in the design and development of PEG-PAL (pegylated Phenylalanine ammonia-lyase) as treatments for mild and classical phenylketonuria (PKU).[74][75][76] In 2008, Stevens started Receptos that developed an S1P1 agonist for multiple sclerosis and inflammatory bowel disease, now on the market called Zeposia and sold by BMS.[77]

Biotechnology Startups

Stevens has started four biotechnology companies (Syrrx (1999), MemRx (2002), Receptos (2009), and RuiYi (2011)), all focused on structure based drug discovery and each company started with one of his former Ph.D. students.

  • Syrrx, started with UC-Berkeley Ph.D. student Nathaniel David and colleague Peter G. Schultz, was acquired by Takeda Pharmaceuticals in 2005 for the high-throughput structure based drug discovery platform, and because of a phase II clinical candidate alogliptin known to inhibit the enzyme DPPIV and is now an approved drug known as Nesina.[78]
  • MemRx, started with Ph.D. student Mike Hanson and Jun Yoon, was acquired by Sagres Discovery in 2003 for the membrane protein expression technologies, and the combined entity was later acquired by Novartis in 2005.
  • Receptos,[79] started with Ph.D. students Mike Hanson, Chris Roth and staff scientist Mark Griffith along with TSRI colleagues Hugh Rosen and Ed Roberts, focused on GPCR structure based drug discovery with a primary interest in inflammation and oncology. On July 14, 2015, Celgene announced that it will buy Receptos for $7.32 billion in cash.[80][81] The S1P1 agonist was approved for patients with MS in March, 2020 under the brand name Zeposia and sold by BMS.[77]
  • In 2011, Stevens, with Paul Grayson and his former TSRI graduate student Fei Xu, started RuiYi, a biologics GPCR company located in Shanghai, China. The company was acquired by Anaphore in 2012.[82] The company currently has one drug in phase II clinical trials for RA and a drug in place for liver fibrosis.
  • In 2018, Stevens, with former students Mike Hanson and Jun Yoon, started Structure Therapeutics,[83] a company focused on converting biologics to small molecules using next generation structure-based drug discovery to make best in class medicines accessible to all. The company currently has two drugs in clinical trials for pulmonary and metabolic diseases.[84]

Awards
  • Named to the PharmaVoice 100 (2022) [85]
  • Elected American Association for the Advancement of Science (AAAS) Fellow (2020)
  • International Scientific Cooperation Award of the Chinese Academy of Sciences (2020)
  • USC Undergraduate Mentor Award (2019)[86]
  • Awarded Magnolia Gold Award of Shanghai (2019)
  • Biophysical Society 2019 Anatrace Membrane Award [87]
  • National PKU Alliance Award (2018) [88]
  • The Protein Society, Stein and Moore Award (2018) [89]
  • Outstanding Faculty Award Shanghai Tech University (2017) [90]
  • Awarded Magnolia Silver Award of Shanghai (2017) [91]
  • International Scientific Collaboration Award of Shanghai (2016)
  • Member, Norwegian Academy of Science and Letters (2016) [92]
  • Thomson Reuters Highly Cited Researcher, 2014 (biology & biochemistry); 2015 (biology & biochemistry; pharmacology & toxicology) and 2016 (biology & biochemistry; pharmacology & toxicology)[93]
  • Qian Ren Award, Chinese Academy of Sciences (Shanghai, China) (2002)
  • Beckman Young Investigators Award (1994)[1]
  • National Science Foundation's Presidential Young Investigator Award (1994)
  • Sidhu Award (1992)

Philanthropy

The John S. Ricci Lecture Hall

Stevens honored his University of Southern Maine professor and mentor, John Ricci, by facilitating the renovation of the lecture hall inside the University science building and renaming it The John S. Ricci Lecture Hall. [94]

The Professor Emeritus John Ricci Undergraduate Fellowships

Established by Stevens to honor USM Professor Emeritus John Ricci and his innovative educational program at Brookhaven National Laboratory, these summer fellowships offer a unique opportunity for USM undergraduates to pursue research at The University of Southern California in Los Angeles, California, one of the oldest private research universities.[95] In 2018, Stevens and his wife supported the building of the John S. Ricci Lecture Hall in honor of his undergraduate teacher and mentor.[96][97]

The Robert Bau Endowed Graduate Fellowship

Established by Stevens and Charles McKenna in 2010 to honor USC distinguished professor Robert Bau after his death in December 2008, the fellowship proposes to help celebrate Professor Bau's life and honor his extraordinary mentorship by linking him to new generations of young chemists at USC.[98]

References
  1. "Raymond C. Stevens". Arnold and Mabel Beckman Foundation. Retrieved 1 August 2018.
  2. https://structuretx.com/
  3. "Danaher Announces Appointment of Raymond C. Stevens, Ph.D. To Danaher Board".
  4. Emerson, Eva (1 October 2007). "Fast-Tracking Lifesaving Discoveries". USC Dornsife. Retrieved 2 August 2018.
  5. Vermont100 race results 2006
  6. American River 50 Miler race results
  7. "26th SULTAN MARATHON DES SABLES". www.darbaroud.com. Archived from the original on 2011-09-03.
  8. Stevens, R. C., & Lipscomb, W. N., "Allosteric Enzymes" Eds., R. Diamond, T. F. Koetzle, K. Prout, & J. Richardson, Molecular Structures in Biology (Oxford, UK: Oxford University Press, 1993) pp. 223–259.
  9. Stebbins, J. W., Robertson, D. E., Roberts, M. F., Stevens, R. C., Lipscomb, W. N., & Kantrowitz, E. R., "Arginine 54 in the active site of Escherichia coli aspartate transcarbamoylase is critical for catalysis: A site-specific mutagenesis, NMR, and X-ray crystallographic study," Prot. Sci. 1, 1435–1446 (1992).
  10. Stevens, R. C., & Lipscomb, W. N., "A molecular mechanism for pyrimidine and purine nucleotide control of aspartate transcarbamylase," Proc. Natl. Acad. Sci. USA 89, 5281–5285 (1992).
  11. Stevens, R. C., Reinisch, K. M., & Lipscomb, W. N., "Molecular Structure of Bacillus subtilis Aspartate transcarbamoylase at 3.0 A Resolution," Proc. Natl. Acad. Sci. USA 88, 6087–6091 (1991).
  12. Stevens, R. C., Chook, Y. M., Cho, C. Y., Lipscomb, W. N., & Kantrowitz, E. R., "Escherichia coli aspartate carbamoyltransferase: The probing of crystal structure analysis via site-specific mutagenesis," Protein Engineering 4, 391–408 (1991).
  13. Gouaux, J. E., Stevens, R. C., & Lipscomb, W. N., "Crystal Structures of Aspartate Carbamoyltransferase Li gated with Phosphonoacetamide, Malonate and CTP or ATP at 2.8-A Resolution and Neutral pH," Biochemistry 29, 7702–7715 (1990).
  14. Stevens, R. C., J.E. Gouaux, & Lipscomb, W. N., "Structural Consequences of Effector Binding to the T State of Aspartate Carbamoyltransferase Crystal Structures of the Unligated and ATP- and CTP-Complexed Enzymes at 2.6-A Resolution," Biochemistry 29, 7691–7701 (1990).
  15. Stevens, R. C., & Lipscomb, W. N., "Allosteric control of quaternary states in E. coli aspartate transcarbamylase," Biochemistry and Biophysics Research Communications 171, 1312–1318 (1990).
  16. Gouaux, J. E., Stevens, R. C., Ke, H., & Lipscomb, W. N., "Crystal structure of the Glu-239 to Gln mutant of aspartate carbamoyltransferase at 3.1 A resolution: An intermediate quaternary structure," Proc. Natl. Acad. Sci. USA 86, 8212–8216 (1989).
  17. H. D. Ulrich, E. Mundorff, B. D. Santarsiero, E. M. Driggers, R. C. Stevens and P. G. Schultz (1997) The interplay between binding energy and catalysis in the evolution of a catalytic antibody Nature 389: 271–5
  18. G. J. Wedemayer, P. A. Patten, L. H. Wang, P. G. Schultz and R. C. Stevens (1997) Structural insights into the evolution of an antibody combining site Science 276: 1665–9
  19. F. E. Romesberg, B. Spiller, P. G. Schultz and R. C. Stevens (1998) Immunological origins of binding and catalysis in a Diels-Alderase antibody Science 279: 1929–33
  20. A. Simeonov, M. Matsushita, E. A. Juban, E. H. Thompson, T. Z. Hoffman, A. E. t. Beuscher, M. J. Taylor, P. Wirsching, W. Rettig, J. K. McCusker, R. C. Stevens, D. P. Millar, P. G. Schultz, R. A. Lerner and K. D. Janda (2000) Blue-fluorescent antibodies Science 290: 307–13
  21. www.jcsg.org
  22. jcimpt.scripps.edu
  23. cmpd.scripps.edu
  24. ihuman.shanghaitech.edu.cn
  25. "The San Diego Union-Tribune - San Diego, California & National News".
  26. R. C. Stevens and I. A. Wilson (2001) Tech.Sight. Industrializing structural biology. Science 293: 519-20
  27. M. A. Hanson, R. C. Stevens (2009) Retraction: Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin type B at 2.0 A resolution Nat Struct Mol Biol. 16(7):795.
  28. M. A. Hanson, T. K. Oost, C. Sukonpan, D. H. Rich, R. C. Stevens (2002) Structural Basis for BABIM Inhibition of Botulinum Neurotoxin Type B Protease [J. Am. Chem. Soc. 2000, 122, 11268−11269] J. Am. Chem. Soc. 124(34):10248–10248
  29. USC College : News : October 2007 : Raymond Stevens
  30. V. Cherezov, D. M. Rosenbaum, M. A. Hanson, S. G. Rasmussen, F. S. Thian, T. S. Kobilka, H. J. Choi, P. Kuhn, W. I. Weis, B. K. Kobilka and R. C. Stevens (2007) High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor Science 318: 1258–65.
  31. V. P. Jaakola, M. T. Griffith, M. A. Hanson, V. Cherezov, E. Y. Chien, J. R. Lane, A. P. Ijzerman and R. C. Stevens (2008) The 2.6 Angstrom Crystal Structure of a Human A2A Adenosine Receptor Bound to an Antagonist, Science 322: 1211–7
  32. B. Wu, E.Y.T. Chien, C.D. Mol, G. Fenalti, W. Liu, V. Katritch, R. Abagyan, A. Brooun, P. Wells, F.C. Bi, D.J. Hamel, P. Kuhn, T.M. Handel, V. Cherezov, R.C. Stevens "Structures of the CXCR4 chemokine GPCR with small molecule and cyclic peptide antagonists" Science 330, 1066-1071 (2010).
  33. E.Y.T. Chien, W. Liu, Q. Zhao, V. Katritch, G.W. Han, M.A. Hanson, L. Shi, A.H. Newman, J.A. Javitch, V. Cherezov, R.C. Stevens "Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist" Science 330, 1091-1095 (2010).
  34. T. Shimamura, M. Shiroishi, S. Weyand, H. Tsujimoto, G. Winter, V. Katritch, R. Abagyan, V. Cherezov, W. Liu, G.W. Han, T. Kobayashi, R.C. Stevens, S. Iwata. "Structure of the human histamine H1 receptor in complex with doxepin" Nature 475, 65-70 (2011).
  35. F. Xu, H. Wu, V. Katritch, G.W. Han, K.A. Jacobson, Z.-G. Gao, V. Cherezov, R.C. Stevens "Structure of an agonist-bound human A2A adenosine receptor" Science 332, 322-327 (2011).
  36. M. A. Hanson, C. B. Roth, E. Jo, M. T. Griffith, F. L. Scott, G. Reinhart, H. Desale, B. Clemons, S. M. Cahalan, S. C. Schuerer, M. G. Sanna, G. W. Han, P. Kuhn, H. Rosen and R. C. Stevens (2012) Crystal structure of a lipid G protein-coupled receptor Science 335: 851-5
  37. H. Wu, D. Wacker, M. Mileni, V. Katritch, G. W. Han, E. Vardy, W. Liu, A. A. Thompson, X. P. Huang, F. I. Carroll, S. W. Mascarella, R. B. Westkaemper, P. D. Mosier, B. L. Roth, V. Cherezov and R. C. Stevens (2012) Structure of the human kappa-opioid receptor in complex with JDTic Nature 485: 327-332
  38. A. A. Thompson, W. Liu, E. Chun, V. Katritch, H. Wu, E. Vardy, X. P. Huang, C. Trapella, R. Guerrini, G. Calo, B. L. Roth, V. Cherezov and R. C. Stevens (2012) Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic Nature 485: 395-9
  39. C. Wang, Y. Jiang, J. Ma, H. Wu, D. Wacker, V. Katritch, G. W. Han, W. Liu, X. P. Huang, E. Vardy, J. D. McCorvy, X. Gao, X. E. Zhou, K. Melcher, C. Zhang, F. Bai, H. Yang, L. Yang, H. Jiang, B. L. Roth, V. Cherezov, R. C. Stevens and H. E. Xu (2013) Structural basis for molecular recognition at serotonin receptors Science 340: 610-4
  40. C. Wang, H. Wu, V. Katritch, G. W. Han, X. P. Huang, W. Liu, F. Y. Siu, B. L. Roth, V. Cherezov and R. C. Stevens (2013) Structure of the human smoothened receptor bound to an antitumour agent Nature 497: 338-43
  41. Q. Tan, Y. Zhu, J. Li, Z. Chen, G. W. Han, I. Kufareva, T. Li, L. Ma, G. Fenalti, J. Li, W. Zhang, X. Xie, H. Yang, H. Jiang, V. Cherezov, H. Liu, R. C. Stevens, Q. Zhao and B. Wu (2013) Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex Science 341: 1387-90
  42. H. Wu, C. Wang, K. J. Gregory, G. W. Han, H. P. Cho, Y. Xia, C. M. Niswender, V. Katritch, J. Meiler, V. Cherezov, P. J. Conn and R. C. Stevens (2014) Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator Science 344: 58-64
  43. J. Zhang, K. Zhang, Z. G. Gao, S. Paoletta, D. Zhang, G. W. Han, T. Li, L. Ma, W. Zhang, C. Müller, H. Yang, H. Jiang, V. Cherezov, V. Katritch, K. A. Jacobson, R. C. Stevens, B. Wu and Q. Zhao (2014) Agonist-bound structure of the human P2Y12 receptor Nature 509: 119-122
  44. K. Zhang, J. Zhang, Z. G. Gao, D. Zhang, L. Zhu, G. W. Han, S. M. Moss, S. Paoletta, E. Kiselev, W. Lu, G. Fenalti, W. Zhang, C. Müller, H. Yang, H. Jiang, V. Cherezov, V. Katritch, K. A. Jacobson, R. C. Stevens, B. Wu and Q. Zhao (2014) Structure of the human P2Y12 receptor in complex with an antithrombotic drug Nature 509: 115-118
  45. G. Fenalti, P. M. Giguere, V. Katritch, X. P. Huang, A. A. Thompson, V. Cherezov, B. L. Roth and R. C. Stevens (2014) Molecular control of delta-opioid receptor signalling Nature 506: 191-6
  46. J.E. Chrencik, C.B. Roth, M. Terakado, H. Kurata, R. Omi, Y. Kihara, D.T. Warshaviak, S. Nakade, G. Asmar-Rovira, M. Mileni, H. Mizuno, M.T. Griffith, C. Rodgers, G.W. Han, J. Velasquez, J. Chun, R.C. Stevens, M.A. Hanson (2015) Crystal structure of human lysophosphatidic acid receptor 1 Cell 161: 1633-1643
  47. H. Zhang, H. Unal, C. Gati, G.W. Han, W. Liu, N.A. Zatsepin, D. James, D. Wang, G. Nelson, U. Weierstall, M.R. Sawaya, Q. Xu, M. Messerschmidt, G.J. Williams, S. Boutet, O.M. Yefanov, T.A. White, C. Wang, A. Ishchenko, K.C. Tirupula, R. Desnoyer, J. Coe, C.E. Conrad, P. Fromme, R.C. Stevens, V. Katritch, S.S. Karnik, V. Cherezov (2015) Structure of the angiotensin receptor revealed by serial femtosecond crystallography Cell 161: 833-844
  48. D. Zhang, Z.G. Gao, K. Zhang, E. Kiselev, S. Crane, J. Wang, S. Paoletta, C. Yi, L. Ma, W. Zhang, G.W. Han, H. Liu, V. Cherezov, V. Katritch, H. Jiang, R.C. Stevens, K.A. Jacobson, Q. Zhao, B. Wu (2015) Two disparate ligand binding sites in the human P2Y1 receptor Nature 520: 317-321
  49. Y. Kang, X. E. Zhou, X. Gao, Y. He, W. Liu, A. Ishchenko, A. Barty, T.A. White, O. Yefanov, G.W. Han, Q. Xu, P.W. de Waal, J. Ke, M. H.E. Tan, C. Zhang, A. Moeller, G.M. West, N. Van Eps, L.N. Caro1, S.A. Vishnivetskiy, R.J. Lee, K.M. Suino-Powell, X. Gu, K. Pal, J. Ma, X. Zhi, S. Boutet, G.J. Williams, M. Messerschmidt, C. Gati, N. A. Zatsepin, D. Wang, D. James, S. Basu, S. Roy-Chowdhury, C. Conrad, J. Coe, H. Liu, S. Lisova, C. Kupitz, I. Grotjohann, R. Fromme, Y. Jiang, M. Tan, H. Yang, J. Li, M. Wang, Z. Zheng, D. Li, N. Howe, Y. Zhao, J. Standfuss, K. Diederichs, Y. Dong, C.S Potter, B. Carragher, M. Caffrey, H. Jiang, H.N. Chapman, J.C. H. Spence, P. Fromme, U. Weierstall, O.P. Ernst, V. Katritch, V.V. Gurevich, P.R. Griffin, W.L. Hubbell, R.C. Stevens, V. Cherezov, K. Melcher, H. E. Xu (2015) Crystal structure of rhodopsin bound to arrestin determined by femtosecond X-ray laser Nature 526: 561-567
  50. T. Hua, K. Vemuri, M. Pu, L. Qu, G.W. Han, Y. Wu, S. Zhao, W. Shui, S. Li, A. Korde, R.B. Laprairie, E.L. Stahl, J.-H. Ho, N. Zvonok, H. Zhou, I. Kufareva, B. Wu, Q. Zhao, M.A. Hanson, L.M. Bohn, A. Makriyannis, R.C. Stevens, Z.-J. Liu (2016) Crystal structure of the human cannabinoid receptor CB1 Cell 167(3): 750-762.e14, 20 October 2016
  51. Y. Zheng, L. Qin, N. V. Zacarías, H. de Vries, G. W. Han, M. Gustavsson, M. Dabros, C. Zhao, R. J. Cherney, P. Carter, D. Stamos, R. Abagyan, V. Cherezov, R. C. Stevens, A. P. IJzerman, L. H. Heitman, A. Tebben, I. Kufareva, T. M. Handel (2016) Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists Nature 540(7633): 458-461
  52. Y. Ma, Y. Yue, Y. Ma, Q. Zhang, Q. Zhou, Y. Song, Y. Shen, X. Li, X. Ma, C. Li, M.A. Hanson, G.W. Han, E.A. Sickmier, G. Swaminath, S. Zhao, R.C. Stevens, L.A. Hu, W. Zhong, M. Zhang, F. Xu “Structural basis for apelin control of the human apelin receptor” Structure 25, 858-866 (2017). (not NIH supported)
  53. H. Zhang, G.W. Han, A. Batyuk, A. Ishchenko, K.L. White, N. Patel, A. Sadybekov, B. Zamlynny, M.T. Rudd, K. Hollenstein, A. Tolstikova, T.A. White, M.S. Hunter, U. Weierstall, W. Liu, K. Babaoglu, E.L. Moore, R.D. Katz, J.M. Shipman, M. Garcia-Calvo, S. Sharma, P. Sheth, S.M. Soisson, R.C. Stevens, V. Katritch, V. Cherezov “Structural basis for selectivity and diversity in angiotensin II receptors” Nature 544, 327-332 (2017). PMC5525545,
  54. H. Zhang, A. Qiao. D. Yang, L. Yang, A. Dai, C. de Graaf, S. Reedtz-Runge, V. Dharmarajan, H. Zhang, G.W. Han, T.D. Grant, R.G. Sierra, U. Weierstall, G. Nelson, W. Liu, Y. Wu, L. Ma, X. Cai, G. Lin, X. Wu, Z. Geng, Y. Dong, G. Song, P.R. Griffin, J. Lau, V. Cherezov, H. Yang, M.A. Hanson, R.C. Stevens, Q. Zhao, H. Jiang, M-W. Wang, B. Wu “Structure of the full-length glucagon class B G protein-coupled receptor” Nature 546, 259-264 (2017). PMC5492955
  55. G. Song, D. Yang, Y. Wang, C. de Graaf, Q. Zhou, S. Jiang, K. Liu, X. Cai, A. Dai, G. Lin, D. Liu, F. Wu, Y. Wu, S. Zhao, L. Ye, G.W. Han, J. Lau, B. Wu, M.A. Hanson, Z-J. Liu, M-W. Wang, R.C. Stevens “Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators” Nature 546, 312-315 (2017). (not NIH supported)
  56. Y. Peng, J.D. McCorvy, K. Harpsoe, K. Lansu, S. Yuan, P. Popov, L. Qu, M. Pu, T. Che, L.F. Nikolajsen, X.P. Huang, Y. Wu, L. Shen, W.E. Bjorn-Yoshimoto, K. Ding, D. Wacker, G.W. Han, J. Cheng, V. Katritch, A.A. Jensen, M.A. Hanson, S. Zhao,D.E. Gloriam, B.L. Roth, R.C. Stevens, Z.J. Liu “5-HT2C receptor structures reveal the structural basis of GPCR polypharmacology” Cell 172, 719-730 (2018). Online 01Feb2018. DOI: 10.1016/j.cell.2018.01.001. PMC6309861,
  57. 364. Z. Yang, S. Han, M. Keller, A. Kaiser, B.J. Bender, M. Bosse, K. Burkert, L.M. Kogler, D. Wifling, G. Bernhardt, N. Plank, T. Littmann, P. Schmidt, C. Yi, B. Li, S. Ye, R. Zhang, B. Xu, D. Larahammar, R.C. Stevens, D. Huster, J. Meiler, Q. Zhao, A.G. Beck-Sickinger, A. Buschauer, B. Wu “Structural basis of ligand binding modes at the neuropeptide Y Y1 receptor” Nature 556, 520-524 (2018). PMC5920736,
  58. C. Cao, Q. Tan, C. Xu, L. He, L. Yang, Y. Zhou, Y. Zhou, A. Qiao, M. Lu, C. Yi, G.W. Han, X. Wang, X. Li, H. Yang, Z. Rao, H. Jiang, Y. Zhao, J. Liu, R.C. Stevens, Q. Zhao, X.C. Zhang, B. Wu “Structural basis for signal recognition and transduction by platelet-activating-factor receptor” Nat Struct Mol Biol 25, 488-495 (2018). doi: 10.1038/s41594-018-0068-y
  59. 370. S. Yang, Y. Wu, T.H. Xu, P.W. de Waal, Y. He, M. Pu, Y. Chen, Z.J. DeBruine, B. Zhang, S.A. Zaidi, P. Popov, Y. Guo, G.W. Han, Y. Lu, K. Suino-Powell, S. Dong, K.G. Harikumar, L.J. Miller, V. Katritch, H.E. Xue, W. Shui, R.C. Stevens, K. Melcher, S. Zhao, F. Xu “Crystal structure of the Frizzled 4 receptor in a ligand-free state” Nature 560, 666-670 (2018). doi: 10.1038/s41586-018-0447-x
  60. M. Audet, K.L. White, B. Breton, B. Zarzycka, G.W. Han, Y. Lu, C. Gati, A. Batyuk, P. Popov, J. Velasquez, D. Manahan, H. Hu, U. Weierstall, W. Liu, W. Shui, V., Katritch, V. Cherezov, M.A. Hanson, R.C. Stevens “Crystal structure of misoprostol bound to the labor inducer prostaglandin E2 receptor” Nat. Chem. Biol. 15:11-17 (2019). doi: 10.1038/s41589-018-0160-y. PMC6289721
  61. X. Li, T. Hua, K. Vemuri, J.H. Ho, Y. Wu, L. Wu, P. Popov, O. Benchama, N. Zvonok, K. Locke, L. Qu, G.W. Han, M.R. Iyer, R. Cinar, N.J. Coffey, J. Wang, M. Wu, V. Katritch, S. Zhao, G. Kunos, L.M. Bohn, A. Makriyannis, R.C. Stevens, Z.J. Liu “Crystal structure of the human cannabinoid receptor CB2” Cell 176, 459-467 (2019). doi: 10.1016/j.cell.2018.12.011 NIHMSID: 1516560
  62. S. Chen, M. Lu, D. Liu, L. yang, C. Ui, L. Ma, H. Zhang, Q. Liu, T.M. Frimurer, M.W. Wang, T.W. Schwartz, R.C. Stevens, B. Wu, K. Wuthrich, Q. Zhao. “Human substance P receptor binding mode of the antagonist drug aprepitant by NMR and crystallography” Nat Commun 10, 638 (2019). doi: 10.1038/s41467-019-08568-5
  63. B. Stauch, L.C. Johansson, J.D. McCorvy, N. Patel, G.W. Han, X.P. Huang, C. Gati, A. Batyuk, S.T. Slocum, A. Ishchenko, W. Brehm, T.A. White, N. Michaelian, C. Madsen, L. Zhu, T.D. Grant, J.M. Grandner, A. Shiriaeva, R.H.J. Olsen, A.R. Tribo, S. Yous, R.C. Stevens, U. Weierstall, V. Katritch, B.L. Roth, W. Liu, V. Cherezov “Structural basis of ligand recognition at the human MT1 melatonin receptor” Nature 569, 289-292 (2019). doi: 10.1038/s41586-019-1141-3. NIHMSID: 1525418
  64. 380. L.C. Johansson, B. Stauch, J.D. McCorvy, G.W. Han, N. Patel, X.P. Huang, A. Batyuk, C. Gati, S.T. Slocum, C. Li, J.M. Grandner, S. Hao, R.H.J. Olsen, A.R. Tribo, S. Zaare, L. Zhu, N.A. Zatsepin, U. Weierstall, S.Yous, R.C. Stevens, W. Liu, B.L. Roth, V. Katritch, V. Cherezov “XFEL structures of the human MT2 melatonin receptor reveal the basis of subtype selectivity” Nature 569, 284-288 (2019). doi: 10.1038/s41586-019-1144-0. PMC6589158
  65. J. Yu, L.E. Gimenez, C.C. Hernandez, Y. Wu, A.H. Wein, G.W. Han, K. McClary, S.R. Mittal, K. Burdsall, B. Stauch, L. Wu, S.N. Stevens, A. Peisley, S.Y. Williams, V. Chen, G.L. Millhauser, S. Zhao, R.D. Cone, R.C. Stevens “Determination of the melanocortin-4 receptor structure identifies Ca2+ as a cofactor for ligand binding” Science 368, 428-433 (2020). online 24 April 2020. doi: 10.1126/science.aaz8995. PMC7567314
  66. Yu, Jing; Gimenez, Luis E.; Hernandez, Ciria C.; Wu, Yiran; Wein, Ariel H.; Han, Gye Won; McClary, Kyle; Mittal, Sanraj R.; Burdsall, Kylie; Stauch, Benjamin; Wu, Lijie; Stevens, Sophia N.; Peisley, Alys; Williams, Savannah Y.; Chen, Valerie; Millhauser, Glenn L.; Zhao, Suwen; Cone, Roger D.; Stevens, Raymond C. (2020). "Determination of the melanocortin-4 receptor structure identifies Ca2+ as a cofactor for ligand binding". Science. 368 (6489): 428–433. Bibcode:2020Sci...368..428Y. doi:10.1126/science.aaz8995. PMC 7567314. PMID 32327598.
  67. "Discovery of protein's configuration could lead to more effective anti-obesity treatments". 23 April 2020.
  68. M. Michino, E. Abola, GPCR Assessment Participants, C.L. Brooks, J.S. Dixon, J. Moult, R.C. Stevens. "Community-wide assessment of GPCR structure modelling and ligand docking: GPCR Dock 2008." Nature Rev. Drug Disc. 8, 455-463 (2009).
  69. I. Kufareva, M. Rueda, V. Katritch, participants of GPCR Dock 2010, R.C. Stevens, R. Abagyan. "Status of GPCR modeling and docking as reflected by community-wide GPCR Dock 2010 assessment" Structure 19, 1108-1126 (2011).
  70. G.M. West, E.Y. Chien, V. Katritch, J. Gatchalian, M.J. Chalmers, R.C. Stevens, P.R. Griffin. "Ligand-dependent perturbation of the conformational ensemble for the GPCR β(2) adrenergic receptor revealed by HDX" Structure. Sept 1 (2011) [Epub ahead of print].
  71. C. U. Kim, W. Lew, M. A. Williams, H. Liu, L. Zhang, S. Swaminathan, N. Bischofberger, M. S. Chen, D. B. Mendel, C. Y. Tai, W. G. Laver and R. C. Stevens (1997) Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity J Am Chem Soc 119: 681–90;
  72. M. A. Williams, W. Lew, D. B. Mendel, C. Y. Tai, P. A. Escarpe, W. G. Laver, R. C. Stevens and C. U. Kim (1997) Structure-activity relationships of carbocyclic influenza neuraminidase inhibitors Bioorg Med Chem Lett 7: 1837–1842;
  73. C. U. Kim, W. Lew, M. A. Williams, H. Wu, L. Zhang, X. Chen, P. A. Escarpe, D. B. Mendel, W. G. Laver and R. C. Stevens (1998) Structure-activity relationship studies of novel carbocyclic influenza neuraminidase inhibitors J Med Chem 41: 2451–60.
  74. H. Erlandsen and R. C. Stevens (1999) The structural basis of phenylketonuria Mol Genet Metab 68: 103–25
  75. L. Wang, A. Gamez, H. Archer, E. E. Abola, C. N. Sarkissian, P. Fitzpatrick, D. Wendt, Y. Zhang, M. Vellard, J. Bliesath, S. M. Bell, J. F. Lemontt, C. R. Scriver and R. C. Stevens (2008) Structural and biochemical characterization of the therapeutic Anabaena variabilis phenylalanine ammonia lyase J Mol Biol 380: 623–35.
  76. T. S. Kang, L. Wang, C. N. Sarkissian, A. Gamez, C. R. Scriver and R. C. Stevens (2010) Converting an injectable protein therapeutic into an oral form: Phenylalanine ammonia lyase for phenylketonuria, Mol Genet Metab 99: 4–9.
  77. "UPDATE: FDA-Approved Oral Zeposia® (Ozanimod) for Relapsing Forms of MS Now Available for Prescripti | National Multiple Sclerosis Society". Nationalmssociety.org. Retrieved 2022-06-21.
  78. Somers, Terri (8 February 2005). "Japanese drug giant taking over Syrrx here". San Diego Union-Tribune. Retrieved 9 August 2016.
  79. www.receptos.com
  80. "$7.3B deal: Celgene will buy drug firm Receptos". USA Today.
  81. "Celgene to acquire Receptos for $7.2 billion". CNBC. 14 July 2015.
  82. www.ruiyibio.com
  83. https://structuretx.com/
  84. "Structure Therapeutics Extends Financing, Advances Diabetes and Obesity Clinical Program and Changes Name from ShouTi" (Press release). August 2022.
  85. "Legacy Leaders: Raymond Stevens".
  86. "Exceptional Mentoring is Key to Building a Supportive Academic Environment". 17 April 2019.
  87. "Raymond Stevens to Receive 2019 BPS Anatrace Membrane Protein Award".
  88. "Home". Npkua.org. Retrieved 2022-06-21.
  89. "The Protein Society : Protein Society Awards".
  90. "ShanghaiTech University".
  91. "50 foreigners receive Magnolia Silver Award in Shanghai". Chinadaily.com.cn. Retrieved 2022-06-21.
  92. "Norwegian Academy of Science and Letters".§
  93. "Thomson Reuters Highly Cited Researchers".§
  94. "World-renowned scientist and USM alumnus recognizes professor & mentor | Office of Public Affairs | University of Southern Maine".
  95. TSRI Stevens Lab: John Ricci Undergraduate Fellowship
  96. "Bill Nemitz: Maine professor, struggling student had a chemistry". Press Herald. April 2018.
  97. "World-renowned scientist and USM alumnus recognizes professor & mentor | Office of Public Affairs | University of Southern Maine".
  98. USC Department of Chemistry: In Memoriaum-Robert Bau
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