Robert J. Lefkowitz

About

Robert J. Lefkowitz is a Duke Health Distinguished Professor of Medicine, as well as a Professor of Medicine, Biochemistry, Pathology, and Chemistry at Duke University. He is a member of the Duke Cancer Institute and an associate of the Duke Initiative for Science & Society. His research focuses on biochemistry and medicine, contributing to the understanding of receptor biology and signaling pathways. Lefkowitz is affiliated with the Duke Department of Biochemistry and conducts his research at the 467 Clinical & Research Labs in Durham, North Carolina.

Research topics

• Biology
• Cell biology
• Biochemistry
• Chemistry
• Computational biology
• Pharmacology
• Internal medicine
• Bioinformatics
• Biotechnology
• Immunology

Selected publications

• Structure of the M2 muscarinic receptor–β-arrestin complex in a lipid nanodisc

  Nature · 2020 · 364 citations

  PublisherOA PDFDOI

• G Protein-Coupled Receptors: A Century of Research and Discovery

  Circulation Research · 2024-06-20 · 144 citations

  reviewOpen access

  GPCRs (G protein-coupled receptors), also known as 7 transmembrane domain receptors, are the largest receptor family in the human genome, with ≈800 members. GPCRs regulate nearly every aspect of human physiology and disease, thus serving as important drug targets in cardiovascular disease. Sharing a conserved structure comprised of 7 transmembrane α-helices, GPCRs couple to heterotrimeric G-proteins, GPCR kinases, and β-arrestins, promoting downstream signaling through second messengers and othe…

  PublisherOA PDFDOI

• GPCR-mediated β-arrestin activation deconvoluted with single-molecule precision

  Cell · 2022-04-27 · 107 citations

  articleOpen access

  β-arrestins bind G protein-coupled receptors to terminate G protein signaling and to facilitate other downstream signaling pathways. Using single-molecule fluorescence resonance energy transfer imaging, we show that β-arrestin is strongly autoinhibited in its basal state. Its engagement with a phosphopeptide mimicking phosphorylated receptor tail efficiently releases the β-arrestin tail from its N domain to assume distinct conformations. Unexpectedly, we find that β-arrestin binding to phosphory…

  PublisherOA PDFDOI

• Synthetic nanobodies as angiotensin receptor blockers

  Proceedings of the National Academy of Sciences · 2020 · 60 citations

  Senior authorCorresponding

  There is considerable interest in developing antibodies as functional modulators of G protein-coupled receptor (GPCR) signaling for both therapeutic and research applications. However, there are few antibody ligands targeting GPCRs outside of the chemokine receptor group. GPCRs are challenging targets for conventional antibody discovery methods, as many are highly conserved across species, are biochemically unstable upon purification, and possess deeply buried ligand-binding sites. Here, we desc…

  PublisherOA PDFDOI

• Signal transduction at GPCRs: Allosteric activation of the ERK MAPK by β-arrestin

  Proceedings of the National Academy of Sciences · 2023-10-16 · 57 citations

  articleOpen accessSenior author

  β-arrestins are multivalent adaptor proteins that bind active phosphorylated G protein-coupled receptors (GPCRs) to inhibit G protein signaling, mediate receptor internalization, and initiate alternative signaling events. β-arrestins link agonist-stimulated GPCRs to downstream signaling partners, such as the c-Raf-MEK1-ERK1/2 cascade leading to ERK1/2 activation. β-arrestins have been thought to transduce signals solely via passive scaffolding by facilitating the assembly of multiprotein signali…

  PublisherDOI

Recent grants

• Molecular Regulation of Cardiovascular 7 TM Receptors

  NIH · $15.2M · 1976–2027

• NIH Grant R01HL070631

  NIH · $3.5M · 2012

• NIH Grant R37HL016037

  NIH · $2.5M · 1996

Frequent coauthors

• Marc G. Caron

  Duke University Hospital

  1396 shared

• Walter J. Koch

  Temple University

  446 shared

• Seungkirl Ahn

  Duke University Hospital

  367 shared

• Louis M. Luttrell

  Medical University of South Carolina

  322 shared

• Brian K. Kobilka

  Stanford University

  273 shared

• Howard A. Rockman

  Duke Medical Center

  260 shared

• Sudha K. Shenoy

  Duke University Health System

  231 shared

• Richard T. Premont

  Case Western Reserve University

  225 shared

Labs

• Lefkowitz LabPI

Education

• B.S., Chemistry

  University of Maryland

  1963

• M.D., Medicine

  Johns Hopkins University School of Medicine

  1967

Similar researchers at Duke University

• Paul Modrichh-148
• Patrick John Caseyh-109
• David N. Beratanh-82