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My lab studies the molecular basis of G protein-coupled receptor (GPCR)-mediated signal transduction using small-angle X-ray scattering, X-ray crystallography, and single particle cryo-electron microscopy (cryo-EM). By determining structures of signaling proteins alone and in complex with their various targets, we provide important insights into the molecular basis of signal transduction, explain how diseases result from dysfunctional regulation, and leverage this information to develop new therapeutic approaches. Since 1999, a focus area has been the structure, function, and inhibition of GPCR kinases (GRKs), a family of 7 enzymes in mammals that phosphorylate activated GPCRs and trigger their uncoupling from G proteins and their internalization. Our lab has a longstanding interest in rational drug design targeting GRKs, whose overexpression in disease states such as heart failure, cardiac hypertrophy, and cancer is linked to poor patient outcome. We also investigate the structure and function of other enzymes of central importance to health, including RhoGEFs essential for neutrophil chemotaxis as well as cancer metastasis and a family of acyltransferases that load HDL particles with cholesterol ester or process excess surfactants in alveolar macrophages. We have a strong extramural funding record and are currently supported by three NIH R01 grants.
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Papers共 272 篇Author StatisticsCo-AuthorSimilar Experts
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Sandeep K Ravala,John Joseph Grubb Tesmer
Molecular pharmacology (2024)
Madison F Walker,Jingyi Zhang, William Steiner,Pei-I Ku,Ju-Fen Zhu, Zachary Michaelson,Yu-Chen Yen, Annabel Lee,Alyssa B Long,Mattie J Casey, Abhishek Poddar,Isaac B Nelson,
bioRxiv : the preprint server for biology (2024)
NATURE STRUCTURAL & MOLECULAR BIOLOGY (2024)
NATURE STRUCTURAL & MOLECULAR BIOLOGY (2024)
Nature structural & molecular biologypp.1-10, (2024)
bioRxiv : the preprint server for biology (2024)
Cancer Researchno. 6_Supplement (2024): 5772-5772
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2024): 115931-115931
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