聚焦胰岛β细胞的跨尺度成像及功能研究。应用多种先进的生物成像技术和分析方法，结合分子生物学、分子遗传学等手段，跨时-空尺度研究胰岛β细胞的信号传导机制及全细胞模型，以期加深对糖尿病等人类疾病机制的理解，并推动新型药物及治疗方案的研发。

Raymond Stevens课题组在糖尿病、肥胖等人类重大疾病相关的G蛋白偶联受体（GPCR）结构生物学及功能研究领域取得多项重大成就（Science, 2020; Nature Communication, 2020; Nature, 2017）。近年来，课题组靶向血糖调控中发挥关键作用的胰岛β细胞，通过跨时-空尺度生物成像手段，打通原子、分子、细胞、组织、活体研究的界限，深入开展生理及病理情况下胰岛β细胞的动态功能研究（部分研究成果发表于Science Advances, 2020a; Science Advances, 2020b; Proc Natl Acad Sci U S A., 2022），为糖尿病等重要代谢类疾病的下一代医疗奠定研究基础。

Raymond Stevens亦积极开展转化研究，其研发的上市药物包括：Nesina, Kuvan, Pegvilase, Zeposia, Botox。

• 1.Amin Guo, Jianhua Zhang, Bo He, Angdi Li, Tianxiao Sun, Weimin Li, Jian Wang, Renzhong Tai, Yan Liu, Zhen Qian, Jiadong Fan, Andrej Sali, Raymond C Stevens, Huaidong Jiang, Quantitative, in situ visualization of intracellular insulin vesicles in pancreatic beta cells, Proc Natl Acad Sci U S A., 2022, 119(32):1-10.

• 2.Raveh B, Sun L, White KL, Sanyal T, Tempkin J, Zheng D, Bharath K, Singla J, Wang C, Zhao J, Li A, Graham NA, Kesselman C, Stevens RC, Sali A. Bayesian metamodeling of complex biological systems across varying representations. Proc Natl Acad Sci U S A. 2021 Aug 31;118(35):e2104559118.

• 3.Zhang M, Qin Q, Zhang S, Liu W, Meng H, Xu M, Huang X, Lin X, Lin M, Herman P, Hyder F, Stevens RC, Wang Z, Li B, Thompson GJ. Aerobic glycolysis imaging of epileptic foci during the inter-ictal period. EBioMedicine. 2022, 79:104004.

• 4.Martin C, Gimenez LE, Williams SY, Jing Y, Wu Y, Hollanders C, Van der Poorten O, Gonzalez S, Van Holsbeeck K, Previti S, Lamouroux A, Zhao S, Tourwé D, Stevens RC, Cone RD, Ballet S. Structure-Based Design of Melanocortin 4 Receptor Ligands Based on the SHU-9119-hMC4R Cocrystal Structure. J Med Chem. 2021 Jan 14;64(1):357-369. doi: 10.1021/acs.jmedchem.0c01620. Epub 2020 Nov 14.

• 5.Hu T, Zheng G, Xue D, Zhao S, Li F, Zhou F, Zhao F, Xie L, Tian C, Hua T, Zhao S, Xu Y, Zhong G, Liu ZJ, Makriyannis A, Stevens RC, Tao H. Rational Remodeling of Atypical Scaffolds for the Design of Photoswitchable Cannabinoid Receptor Tools. J Med Chem. 2021 Sep 23;64(18):13752-13765. doi:10.1021/acs.jmedchem.1c01088. Epub 2021 Sep 3. PMID: 34477367.

• 6.Zhao F, Zhang C, Zhou Q, Hang K, Zou X, Chen Y, Wu F, Rao Q, Dai A, Yin W, Shen DD, Zhang Y, Xia T, Stevens RC, Xu HE, Yang D, Zhao L, Wang MW. Structural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor. Elife. 2021 Jul 13;10:e68719. doi: 10.7554/eLife.68719.

• 7.Li A, Zhang X, Singla J, White K, Loconte V, Hu C, Zhang C, Li S, Li W, Francis JP, Wang C, Sali A, Sun L, He X, Stevens RC. Auto-segmentation and time-dependent systematic analysis of mesoscale cellular structure in β-cells during insulin secretion. PLoS One. 2022 Mar 24;17(3):e0265567.

• 8.White, Kate L.,Sali, Andrej;Larabell, Carolyn;Stevens, Raymond C.;,White, Kate L.;Singla, Jitin;Loconte, Valentina;Chen, Jian-Hua;Ekman, Axel;Sun, Liping;Zhang, Xianjun;Francis, John Paul;Li, Angdi;Lin, Wen;Tseng, Kaylee;McDermott, Gerry;Alber, Frank;Sali, Andrej;Larabell, Carolyn;Stevens, Raymond C.,Visualizing subcellular rearrangements in intact beta cells using soft x-ray tomography,http://doi.org/10.1126/sciadv.abc8262,SCIENCE ADVANCES,Dec 2020,6(50),10.1126/sciadv.abc8262

• 9.Zhang, X.;Carter, S. D.;Singla, J.;White, K.L.;Butler, P. C.;Stevens, R.C.^*, Jensen, G. J^*.Visualizing insulin vesicle neighborhoods in β cells by cryo-electron tomography. Sci Adv, 2020,6(50): eabc8258.

• 10.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.,Determination of the melanocortin-4 receptor structure identifies Ca2+ as a cofactor for ligand binding,http://doi.org/10.1126/science.aaz8995,SCIENCE,24 Apr 2020,368(6489):428-+,10.1126/science.aaz8995

• 11.Wu, Fan;Yang, Linlin;Hang, Kaini;Laursen, Mette;Wu, Lijie;Han, Gye Won;Ren, Qiansheng;Roed, Nikolaj Kulahin;Lin, Guangyao;Hanson, Michael A.;Jiang, Hualiang;Wang, Ming-Wei;Reedtz-Runge, Steffen;Song, Gaojie;Stevens, Raymond C.,Full-length human GLP-1 receptor structure without orthosteric ligands,http://doi.org/10.1038/s41467-020-14934-5,NATURE COMMUNICATIONS,09 Mar 2020,11(1),10.1038/s41467-020-14934-5

• 12.Qin, Q.;Thompson, G. J.;Stevens, R. C.,MRI-Based Perspective on Virtual Organ,JOURNAL OF BIOENERGETICS AND BIOMEMBRANES,Dec 2018,50(6):574-575

• 13.Peng, Yao;McCorvy, John D.;Harpsoe, Kasper;Lansu, Katherine;Yuan, Shuguang;Popov, Petr;Qu, Lu;Pu, Mengchen;Che, Tao;Nikolajsen, Louise F.;Huang, Xi-Ping;Wu, Yiran;Shen, Ling;Bjorn-Yoshimoto, Walden E.;Ding, Kang;Wacker, Daniel;Han, Gye Won;Cheng, Jianjun;Katritch, Vsevolod;Jensen, Anders A.;Hanson, Michael A.;Zhao, Suwen;Gloriam, David E.;Roth, Bryan L.;Stevens, Raymond C.;Liu, Zhi-Jie,5-HT2C Receptor Structures Reveal the Structural Basis of GPCR. Polypharmacology,CELL,08 Feb 2018,172(4):719-+,10.1016/j.cell.2018.01.001

• 14.Hua, Tian;Vemuri, Kiran;Nikas, Spyros P.;Laprairie, Robert B.;Wu, Yiran;Qu, Lu;Pu, Mengchen;Korde, Anisha;Jiang, Shan;Ho, Jo-Hao;Han, Gye Won;Ding, Kang;Li, Xuanxuan;Liu, Haiguang;Hanson, Michael A.;Zhao, Suwen;Bohn, Laura M.;Makriyannis, Alexandros;Stevens, Raymond C.;Liu, Zhi-Jie,Crystal structures of agonist-bound human cannabinoid receptor CB1,http://doi.org/10.1038/nature23272,NATURE,27 Jul 2017,547(7664):468-+,10.1038/nature23272

• 15.Hua, Tian;Vemuri, Kiran;Pu, Mengchen;Qu, Lu;Han, Gye Won;Wu, Yiran;Zhao, Suwen;Shui, Wenqing;Li, Shanshan;Korde, Anisha;Laprairie, Robert B.;Stahl, Edward L.;Ho, Jo-Hao;Zvonok, Nikolai;Zhou, Han;Kufareva, Irina;Wu, Beili;Zhao, Qiang;Hanson, Michael A.;Bohn, Laura M.;Makriyannis, Alexandros;Stevens, Raymond C.;Liu, Zhi-Jie,Crystal Structure of the Human Cannabinoid Receptor CB1,http://doi.org/10.1016/j.cell.2016.10.004,CELL,2016,167(3):750-762,10.1016/j.cell.2016.10.004

• 16.Zhang, Haonan,Jiang, Hualiang;Wang, Ming-Wei;Wu, Beili;,Zhang, Haonan;Qiao, Anna;Yang, Dehua;Yang, Linlin;Dai, Antao;De Graaf, Chris;Reedtz-Runge, Steffen;Dharmarajan, Venkatasubramanian;Zhang, Hui;Han, Gye Won;Grant, Thomas D.;Sierra, Raymond G.;Weierstall, Uwe;Nelson, Garrett;Liu, Wei;Wu, Yanhong;Ma, Limin;Cai, Xiaoqing;Lin, Guangyao;Wu, Xiaoai;Geng, Zhi;Dong, Yuhui;Song, Gaojie;Griffin, Patrick R.;Lau, Jesper;Chrezov, Vadim;Yang, Huaiyu;Hanson, Michael A.;Stevens, Raymond C.;Zhao, Qiang;Jiang, Hualiang;Wang, Ming-Wei;Wu, Beili,Structure of the full-length glucagon class B G-protein-coupled receptor,http://doi.org/10.1038/nature22363,NATURE,08 Jun 2017,546(7657):259-+,10.1038/nature22363

• 17.Wu, Fan;Song, Gaojie;de Graaf, Chris;Stevens, Raymond C.,Structure and Function of Peptide-Binding G Protein-Coupled Receptors,http://doi.org/10.1016/j.jmb.2017.06.022,JOURNAL OF MOLECULAR BIOLOGY,18 Aug 2017,429(17):2726-2745,10.1016/j.jmb.2017.06.022
  

• 18.Song, Gaojie;Yang, Dehua;Wang, Yuxia;de Graaf, Chris;Zhou, Qingtong;Jiang, Shanshan;Liu, Kaiwen;Cai, Xiaoqing;Dai, Antao;Lin, Guangyao;Liu, Dongsheng;Wu, Fan;Wu, Yiran;Zhao, Suwen;Ye, Li;Han, Gye Won;Lau, Jesper;Wu, Beili;Hanson, Michael A.;Liu, Zhi-Jie;Wang, Ming-Wei;Stevens, Raymond C.,Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators, NATURE,08 Jun 2017,546(7657):312