Raymond C. Stevens

Raymond C. Stevens (born 1963) is an American chemist and structural biologist, Director of the iHuman Institute, ShanghaiTech University and Provost Professor of Biological Sciences and Chemistry, and Director of the Bridge Institute at the 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 Professors Robert Bau and George Olah. He completed his Ph.D. in 26 months, graduating in 1988.[1]

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[2] and American River 50 Mile Endurance Run,[3] and in 2011 he successfully completed the 156 mile Marathon des Sables[4] across the Moroccan Sahara Desert.

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.[5][6][7][8][9][10][11][12][13] 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.[14][15][16][17] 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,[18] Joint Center for Innovative Membrane Protein Technologies,[19] and the GPCR Network,[20] all funded by the National Institutes of Health with direct guidance from NIGMS. In 2012, Stevens was recruited to found the iHuman Institute at ShanghaiTech University.[21] 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.[22]

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.[23] 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.[24][25]

In October 2007, Stevens and colleagues published the first high-resolution structure of a human GPCR.[26][27] 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,[28] also known as the caffeine receptor. In 2010, the structures of the human chemokine CXCR4 receptor (HIV co-receptor),[29] the human dopamine D3 receptor[30] and the human Histamine H1 receptor [31] were published. In addition to these inactive-state structures, Stevens and colleagues solved the structure of an agonist-bound A2A adenosine receptor.[32]

Subsequent novel human receptor structures include:

2012: The first structure of a lipid-activated GPCR, the sphingolipid,[33] the human kappa-opioid receptor [34] and the human nociceptin/orphanin FQ peptide.[35]

2013: Serotonin receptors 5-HT1B and 5-HT2B,[36][37] the second HIV co-receptor, C-C chemokine receptor type 5 (CCR5) [38] and the first structure of a class C GPCR, the transmembrane domain of the human Metabotropic glutamate receptor 1 (mGluR1) [39] and the first structures of non-class A 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 family.

2014: The human P2Y receptor 12 (P2Y12) bound to antagonist or agonist;[41][42] the human Delta opioid receptor at 1.8A [43] and the first structure of a class C GPCR, the transmembrane domain of the human Metabotropic glutamate receptor 1 (mGluR1).[44]

2015: The human Lysophosphatidic acid receptor 1 (LPAR1),[45] the human angiotensin II receptor type 1 (AT1R),[46] human P2Y receptor 1 (P2Y1);[47] and the human Rhodopsin-Arrestin complex.[48]

2016: The marijuana receptor—human Cannabinoid receptor type 1 (CB1) [49] and the human C-C chemokine receptor type 2 (CCR2) [50]

In combination with the structural studies, working with the computational biology community to conduct GPCR Dock 2008[51] and GPCR Dock 2010[52] has helped to evaluate where the field is at, and functional studies using HDX[53] 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,[54][55][56] and later partnered with Roche. After the initial experience with structure based drug discovery from 1992–1997 with Gilead and Tamiflu, Stevens focused on understanding the basic mechanism of how BotoxTM (botulinum toxin) works, and on ways to use this scaffold for next generation protein therapeutics. In parallel to the work on botulinum toxin, Stevens worked on the enzymes involved in the catecholamine biosynthetic pathway, specifically the three aromatic amino acid hydroxylases including phenylalanine hydroxylase. From 1999-2004 Stevens was involved in the startup of Syrrx that developed the marketed drug Nesina for type II diabetes. From 2000–2010, Stevens has worked with BioMarin Pharmaceutical to develop KuvanTM (tetrahydrobiopterin) and assisted in the design and development of PEG-PAL (pegylated Phenylalanine ammonia-lyase) as treatments for mild and classical phenylketonuria (PKU).[57][58][59] In 2008 Stevens started Receptos that developed an S1P1 agonist for multiple sclerosis and inflammatory bowel disease and in 2011 he started RuiYi that developed an anti-CB1 antibody for liver fibrosis.

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.

Awards

Philanthropy

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 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.[68]

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.[69]

References

  1. ↑ Fast-Tracking Lifesaving Discoveries, USC Newsletter, 1 October 2007
  2. ↑ Vermont100 race results 2006)
  3. ↑ American River 50 Miler race results
  4. ↑
  5. ↑ 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.
  6. ↑ 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).
  7. ↑ 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).
  8. ↑ 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).
  9. ↑ 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).
  10. ↑ 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).
  11. ↑ 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).
  12. ↑ 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).
  13. ↑ 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).
  14. ↑ 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
  15. ↑ 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
  16. ↑ 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
  17. ↑ 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
  18. ↑ www.jcsg.org
  19. ↑ jcimpt.scripps.edu
  20. ↑ cmpd.scripps.edu
  21. ↑ ihuman.shanghaitech.edu.cn
  22. ↑ http://www.utsandiego.com/news/2014/jun/23/tamiflu-USC/
  23. ↑ R. C. Stevens and I. A. Wilson (2001) Tech.Sight. Industrializing structural biology. Science 293: 519-20
  24. ↑ 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.
  25. ↑ 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
  26. ↑ USC College : News : October 2007 : Raymond Stevens
  27. ↑ 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.
  28. ↑ 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
  29. ↑ 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).
  30. ↑ 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).
  31. ↑ 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).
  32. ↑ 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).
  33. ↑ 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
  34. ↑ 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
  35. ↑ 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
  36. ↑ 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
  37. ↑ 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
  38. ↑ 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
  39. ↑ 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
  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. ↑ 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
  42. ↑ 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
  43. ↑ 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
  44. ↑ 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
  45. ↑ 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
  46. ↑ 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
  47. ↑ 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
  48. ↑ 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
  49. ↑ 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
  50. ↑ 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
  51. ↑ 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).
  52. ↑ 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).
  53. ↑ 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].
  54. ↑ 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;
  55. ↑ 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;
  56. ↑ 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.
  57. ↑ H. Erlandsen and R. C. Stevens (1999) The structural basis of phenylketonuria Mol Genet Metab 68: 103–25
  58. ↑ 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.
  59. ↑ 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.
  60. ↑ Somers, Terri (8 February 2005). "Japanese drug giant taking over Syrrx here". San Diego Union-Tribune. Retrieved 9 August 2016.
  61. ↑ www.receptos.com
  62. ↑ http://www.usatoday.com/story/money/business/2015/07/14/celgene-receptos/30168919/
  63. ↑ http://www.cnbc.com/2015/07/14/celgene-to-acquire-receptos-for-more-than-7b.html
  64. ↑ www.ruiyibio.com
  65. ↑ "Norwegian Academy of Science and Letters".§
  66. ↑ "Thomson Reuters Highly Cited Researchers".§
  67. ↑ "Raymond C. Stevens". Arnold and Mabel Beckman Foundation. Retrieved 9 March 2017.
  68. ↑ TSRI Stevens Lab: John Ricci Undergraduate Fellowship
  69. ↑ USC Department of Chemistry: In Memoriaum-Robert Bau
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