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The Benovic laboratory studies the molecular and cellular basis of G protein-coupled receptor (GPCR) signaling with a primary focus on the biochemistry and cell biology of GPCR kinases (GRKs) and arrestins and understanding how dysregulation of GPCRs and G proteins contributes to the development of disease. We have significant experience studying arrestin-mediated regulation of GPCRs, such as the β2-adrenergic receptor (β2AR) and the chemokine receptor CXCR4. This work has involved extensive characterization of the mechanisms involved in receptor phosphorylation and arrestin binding, the structural basis for GRK and arrestin interaction with GPCRs, and how these processes regulate signaling and trafficking. We have also developed strategies to bias GPCR signaling with our initial efforts focused on the use of peptides and small molecules to mediate biased signaling through the β2AR. In addition, we study the role of Gq signaling in airway disease and uveal melanoma and are currently trying to develop inhibitors to treat these diseases. Overall, we utilize a variety of strategies in our work including biophysical approaches, biochemical and genetic analysis, and molecular and cellular biology. There are currently five primary areas of research in the lab.
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Pharmacological reviewsno. 2 (2024): 267-299
crossref(2023)
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS (2023)
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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS (2023)
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Proceedings of the National Academy of Sciences of the United States of Americano. 31 (2023): e2302668120-e2302668120
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Dominic Lapadula,Bao Lam,Mizue Terai,Takahito Sugase,Ryota Tanaka,Eduardo Farias,Rama Kadamb, Melisa Lopez-Anton, Christian C. Heine, Bhavik Modasia, Julio A. Aguirre-Ghiso,Andrew E. Aplin,
Usman Baqai,Alison M. Kurimchak, Isabella V. Trachtenberg,Timothy J. Purwin, Jelan I. Haj,Anna Han, Kristine Luo, Nikole Fandino Pachon, Angela Jeon,J. Silvio Gutkind,Vivian Chua,Michael A. Davies,
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