Raymond Stevens
University of Southern California
H-index: 133
North America-United States
Description
Raymond Stevens, With an exceptional h-index of 133 and a recent h-index of 80 (since 2020), a distinguished researcher at University of Southern California, specializes in the field of human imaging.
His recent articles reflect a diverse array of research interests and contributions to the field:
Conjunctive encoding of exploratory intentions and spatial information in the hippocampus
Novel Cocrystal Structures of Peptide Antagonists Bound to the Human Melanocortin Receptor 4 Unveil Unexplored Grounds for Structure-Based Drug Design
In situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography
Conformational Dynamics of the Activated GLP-1 Receptor-Gs Complex Revealed by Cross-Linking Mass Spectrometry and Integrative Structure Modeling
Structural insights into the human niacin receptor HCA2-Gi signalling complex
Affinity selection of double-click triazole libraries for rapid discovery of allosteric modulators for GLP-1 receptor
GLP-1R signaling and functional molecules in incretin therapy
Discovery of G-protein Biased APJ Agonist Small Molecule for Pulmonary Diseases
Professor Information
University | University of Southern California |
---|---|
Position | iHuman Institute ShanghaiTech/Bridge Institute |
Citations(all) | 74181 |
Citations(since 2020) | 24006 |
Cited By | 61048 |
hIndex(all) | 133 |
hIndex(since 2020) | 80 |
i10Index(all) | 392 |
i10Index(since 2020) | 253 |
University Profile Page | University of Southern California |
Research & Interests List
human imaging
Top articles of Raymond Stevens
Conjunctive encoding of exploratory intentions and spatial information in the hippocampus
The hippocampus creates a cognitive map of the external environment by encoding spatial and self-motion-related information. However, it is unclear whether hippocampal neurons could also incorporate internal cognitive states reflecting an animal’s exploratory intention, which is not driven by rewards or unexpected sensory stimuli. In this study, a subgroup of CA1 neurons was found to encode both spatial information and animals’ investigatory intentions in male mice. These neurons became active before the initiation of exploration behaviors at specific locations and were nearly silent when the same fields were traversed without exploration. Interestingly, this neuronal activity could not be explained by object features, rewards, or mismatches in environmental cues. Inhibition of the lateral entorhinal cortex decreased the activity of these cells during exploration. Our findings demonstrate that hippocampal neurons …
Authors
Yi-Fan Zeng,Ke-Xin Yang,Yilong Cui,Xiao-Na Zhu,Rui Li,Hanqing Zhang,Dong Chuan Wu,Raymond C Stevens,Ji Hu,Ning Zhou
Journal
Nature Communications
Published Date
2024/4/15
Novel Cocrystal Structures of Peptide Antagonists Bound to the Human Melanocortin Receptor 4 Unveil Unexplored Grounds for Structure-Based Drug Design
Melanocortin 4 receptor (MC4-R) antagonists are actively sought for treating cancer cachexia. We determined the structures of complexes with PG-934 and SBL-MC-31. These peptides differ from SHU9119 by substituting His6 with Pro6 and inserting Gly10 or Arg10. The structures revealed two subpockets at the TM7-TM1-TM2 domains, separated by N2857.36. Two peptide series based on the complexed peptides led to an antagonist activity and selectivity SAR study. Most ligands retained the SHU9119 potency, but several SBL-MC-31-derived peptides significantly enhanced MC4-R selectivity over MC1-R by 60- to 132-fold. We also investigated MC4-R coupling to the K+ channel, Kir7.1. Some peptides activated the channel, whereas others induced channel closure independently of G protein coupling. In cell culture studies, channel activation correlated with increased feeding, while a peptide with Kir7.1 …
Authors
Luis E Gimenez,Charlotte Martin,Jing Yu,Charlie Hollanders,Ciria C Hernandez,Yiran Wu,Deqiang Yao,Gye Won Han,Naima S Dahir,Lijie Wu,Olivier Van der Poorten,Arthur Lamouroux,Morgane Mannes,Suwen Zhao,Dirk Tourwé,Raymond C Stevens,Roger D Cone,Steven Ballet
Journal
Journal of Medicinal Chemistry
Published Date
2024/2/12
In situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography
Actin mediates insulin secretion in pancreatic β-cells through remodeling. Hampered by limited resolution, previous studies have offered an ambiguous depiction as depolymerization and repolymerization. We report the in situ structure of actin remodeling in INS-1E β-cells during glucose-stimulated insulin secretion at nanoscale resolution. After remodeling, the actin filament network at the cell periphery exhibits three marked differences: 12% of actin filaments reorient quasi-orthogonally to the ventral membrane; the filament network mainly remains as cell-stabilizing bundles but partially reconfigures into a less compact arrangement; actin filaments anchored to the ventral membrane reorganize from a “netlike” to a “blooming” architecture. Furthermore, the density of actin filaments and microtubules around insulin secretory granules decreases, while actin filaments and microtubules become more densely packed …
Authors
Weimin Li,Angdi Li,Bing Yu,Xiaoxiao Zhang,Xiaoyan Liu,Kate L White,Raymond C Stevens,Wolfgang Baumeister,Andrej Sali,Marion Jasnin,Liping Sun
Journal
Nature Communications
Published Date
2024/2/12
Conformational Dynamics of the Activated GLP-1 Receptor-Gs Complex Revealed by Cross-Linking Mass Spectrometry and Integrative Structure Modeling
Despite advances in characterizing the structures and functions of G protein-coupled receptors (GPCRs), our understanding of GPCR activation and signaling is still limited by the lack of information on conformational dynamics. It is particularly challenging to study the dynamics of GPCR complexes with their signaling partners because of their transient nature and low stability. Here, by combining cross-linking mass spectrometry (CLMS) with integrative structure modeling, we map the conformational ensemble of an activated GPCR-G protein complex at near-atomic resolution. The integrative structures describe heterogeneous conformations for a high number of potential alternative active states of the GLP-1 receptor–Gs complex. These structures show marked differences from the previously determined cryo-EM structure, especially at the receptor–Gs interface and in the interior of the Gs heterotrimer. Alanine …
Authors
Shijia Yuan,Lisha Xia,Chenxi Wang,Fan Wu,Bingjie Zhang,Chen Pan,Zhiran Fan,Xiaoguang Lei,Raymond C Stevens,Andrej Sali,Liping Sun,Wenqing Shui
Journal
ACS Central Science
Published Date
2023/4/24
Structural insights into the human niacin receptor HCA2-Gi signalling complex
The hydroxycarboxylic acid receptor 2 (HCA2) agonist niacin has been used as treatment for dyslipidemia for several decades albeit with skin flushing as a common side-effect in treated individuals. Extensive efforts have been made to identify HCA2 targeting lipid lowering agents with fewer adverse effects, despite little being known about the molecular basis of HCA2 mediated signalling. Here, we report the cryo-electron microscopy structure of the HCA2-Gi signalling complex with the potent agonist MK-6892, along with crystal structures of HCA2 in inactive state. These structures, together with comprehensive pharmacological analysis, reveal the ligand binding mode and activation and signalling mechanisms of HCA2. This study elucidates the structural determinants essential for HCA2 mediated signalling and provides insights into ligand discovery for HCA2 and related receptors.
Authors
Yang Yang,Hye Jin Kang,Ruogu Gao,Jingjing Wang,Gye Won Han,Jeffrey F DiBerto,Lijie Wu,Jiahui Tong,Lu Qu,Yiran Wu,Ryan Pileski,Xuemei Li,Xuejun Cai Zhang,Suwen Zhao,Terry Kenakin,Quan Wang,Raymond C Stevens,Wei Peng,Bryan L Roth,Zihe Rao,Zhi-Jie Liu
Journal
Nature communications
Published Date
2023/3/27
Affinity selection of double-click triazole libraries for rapid discovery of allosteric modulators for GLP-1 receptor
The recently developed double-click reaction sequence [G. Meng et al., Nature 574, 86–89 (2019)] is expected to vastly expand the number and diversity of synthetically accessible 1,2,3-triazole derivatives. However, it remains elusive how to rapidly navigate the extensive chemical space created by double-click chemistry for bioactive compound discovery. In this study, we selected a particularly challenging drug target, the glucagon-like-peptide-1 receptor (GLP-1R), to benchmark our new platform for the design, synthesis, and screening of double-click triazole libraries. First, we achieved a streamlined synthesis of customized triazole libraries on an unprecedented scale (composed of 38,400 new compounds). By interfacing affinity-selection mass spectrometry and functional assays, we identified a series of positive allosteric modulators (PAMs) with unreported scaffolds that can selectively and robustly enhance the …
Authors
Ye Xin,Shuo Liu,Yan Liu,Zhen Qian,Hongyue Liu,Bingjie Zhang,Taijie Guo,Garth J Thompson,Raymond C Stevens,K Barry Sharpless,Jiajia Dong,Wenqing Shui
Journal
Proceedings of the National Academy of Sciences
Published Date
2023/3/14
GLP-1R signaling and functional molecules in incretin therapy
Glucagon-like peptide-1 receptor (GLP-1R) is a critical therapeutic target for type 2 diabetes mellitus (T2DM). The GLP-1R cellular signaling mechanism relevant to insulin secretion and blood glucose regulation has been extensively studied. Numerous drugs targeting GLP-1R have entered clinical treatment. However, novel functional molecules with reduced side effects and enhanced therapeutic efficacy are still in high demand. In this review, we summarize the basis of GLP-1R cellular signaling, and how it is involved in the treatment of T2DM. We review the functional molecules of incretin therapy in various stages of clinical trials. We also outline the current strategies and emerging techniques that are furthering the development of novel therapeutic drugs for T2DM and other metabolic diseases.
Authors
Wenwei Wan,Qikai Qin,Linshan Xie,Hanqing Zhang,Fan Wu,Raymond C Stevens,Yan Liu
Published Date
2023/1/11
Discovery of G-protein Biased APJ Agonist Small Molecule for Pulmonary Diseases
Rationale The regulatory peptide apelin and its receptor APJ are widely expressed in pulmonary and cardiovascular tissue. Apelin peptide administration is demonstrably effective in various preclinical disease models. However, the apelin peptide is not a viable therapeutic due to its short half-life, induction of receptor tachyphylaxis, and requirement for intravenous administration. Utilizing our unique structure-based drug discovery platform, we have discovered a novel series of small molecule APJ agonists with improved pharmaceutical properties and biased signaling along the cAMP/G-protein pathway. Our biased APJ agonists provide new treatment opportunities for chronic diseases by aiming to minimize receptor tachyphylaxis and avoid β-arrestin-associated pharmacology such as cardiac hypertrophy and systemic blood pressure reduction. Methods RNAscope technology was utilized to visualize APJ …
Authors
S Shi,C Guan,F Zhang,J Zhang,H Lei,X Lin,RC Stevens,MA Hanson
Published Date
2023/5
Professor FAQs
What is Raymond Stevens's h-index at University of Southern California?
The h-index of Raymond Stevens has been 80 since 2020 and 133 in total.
What are Raymond Stevens's top articles?
The articles with the titles of
Conjunctive encoding of exploratory intentions and spatial information in the hippocampus
Novel Cocrystal Structures of Peptide Antagonists Bound to the Human Melanocortin Receptor 4 Unveil Unexplored Grounds for Structure-Based Drug Design
In situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography
Conformational Dynamics of the Activated GLP-1 Receptor-Gs Complex Revealed by Cross-Linking Mass Spectrometry and Integrative Structure Modeling
Structural insights into the human niacin receptor HCA2-Gi signalling complex
Affinity selection of double-click triazole libraries for rapid discovery of allosteric modulators for GLP-1 receptor
GLP-1R signaling and functional molecules in incretin therapy
Discovery of G-protein Biased APJ Agonist Small Molecule for Pulmonary Diseases
...
are the top articles of Raymond Stevens at University of Southern California.
What are Raymond Stevens's research interests?
The research interests of Raymond Stevens are: human imaging
What is Raymond Stevens's total number of citations?
Raymond Stevens has 74,181 citations in total.