About

Bob Roth is a faculty member at the UNC School of Medicine, specializing in inflammation as a determinant of sensitivity to toxic agents. His research focuses on understanding the role of inflammation in mediating the effects of various toxic agents, which is critical for assessing health risks associated with environmental exposures. His work aims to elucidate the mechanisms by which inflammatory processes influence susceptibility to toxic substances, contributing to the broader field of toxicology and environmental health.

Research topics

• Biochemistry
• Biology
• Pharmacology
• Chemistry
• Medicine
• Stereochemistry
• Biophysics
• Computational biology
• Cell biology
• Psychology
• Immunology
• Genetics
• Virology
• Neuroscience
• Bioinformatics

Selected publications

• Neurotensin Receptor Allosterism Revealed in Complex with a Biased Allosteric Modulator

  Biochemistry · 2023 · 69 citations

  Senior authorCorresponding
  • Chemistry
  • Biochemistry
  • Cell biology

  The NTSR1 neurotensin receptor (NTSR1) is a G protein-coupled receptor (GPCR) found in the brain and peripheral tissues with neurotensin (NTS) being its endogenous peptide ligand. In the brain, NTS modulates dopamine neuronal activity, induces opioid-independent analgesia, and regulates food intake. Recent studies indicate that biasing NTSR1 toward β-arrestin signaling can attenuate the actions of psychostimulants and other drugs of abuse. Here, we provide the cryoEM structures of NTSR1 ternary complexes with heterotrimeric Gq and GoA with and without the brain-penetrant small-molecule SBI-553. In functional studies, we discovered that SBI-553 displays complex allosteric actions exemplified by negative allosteric modulation for G proteins that are Gα subunit selective and positive allosteric modulation and agonism for β-arrestin translocation at NTSR1. Detailed structural analysis of the allosteric binding site illuminated the structural determinants for biased allosteric modulation of SBI-553 on NTSR1.

  PublisherDOI

• Structure-based design of bitopic ligands for the µ-opioid receptor

  Nature · 2022 · 126 citations

  • Chemistry
  • Pharmacology
  • Stereochemistry
  PublisherOA PDFDOI

• Bespoke library docking for 5-HT2A receptor agonists with antidepressant activity

  Nature · 2022 · 248 citations

  • Chemistry
  • Pharmacology
  • Biophysics
  DOI

• The neural basis of psychedelic action

  Nature Neuroscience · 2022 · 283 citations

  Senior authorCorresponding
  • Neuroscience
  • Psychology
  DOI

• Controlling opioid receptor functional selectivity by targeting distinct subpockets of the orthosteric site

  eLife · 2021 · 66 citations

  • Chemistry
  • Pharmacology
  • Biology

  displayed MOR/KOR Gi-partial agonism with diminished arrestin signaling, showed efficient analgesia with attenuated liabilities, including respiratory depression and conditioned place preference and aversion in mice. The findings validate a novel structure-inspired paradigm for achieving beneficial in vivo profiles for analgesia through different mechanisms that include bias, partial agonism, and dual MOR/KOR agonism.

  PublisherDOI

• Structure, function and pharmacology of human itch GPCRs

  Nature · 2021 · 221 citations

  Senior authorCorresponding
  • Pharmacology
  • Cell biology
  • Chemistry
  DOI

• A Novel Mitragynine Analog with Low-Efficacy Mu Opioid Receptor Agonism Displays Antinociception with Attenuated Adverse Effects

  Journal of Medicinal Chemistry · 2021 · 74 citations

  • Chemistry
  • Pharmacology
  • Stereochemistry

  with reduced opioid liabilities.

  PublisherOA PDFDOI

• A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

  Nature · 2020 · 4839 citations

  • Virology
  • Biology
  • Pharmacology
  DOI

Recent grants

• NIH Grant R01MH061887

  NIH · $4.5M · 2016

• NIH Grant R01MH057635

  NIH · $2.5M · 2007

• NIH Grant R01DA017204

  NIH · $3.2M · 2016

• Illuminating the Druggable GPCR-ome

  NIH · $2.2M · 2017–2023

• Mechanistic insights into LSD actions at 5-HT2A serotonin receptors

  NIH · $5.8M · 2023–2028

Frequent coauthors

• Xi‐Ping Huang

  Guangzhou University of Chinese Medicine

  306 shared

• Vincent Setola

  University of the West

  163 shared

• William C. Wetsel

  Duke University

  95 shared

• John D. McCorvy

  Medical College of Wisconsin

  92 shared

• Jordan K. Zjawiony

  University of Mississippi

  86 shared

• Brian K. Shoichet

  University of California, San Francisco

  81 shared

• Richard B. Westkaemper

  78 shared

• Richard A. Glennon

  Virginia Commonwealth University

  72 shared

Similar researchers at University of North Carolina at Chapel Hill

• Barry M. Popkinh-170
• Cynthia Bulikh-134
• Doug Perkinsh-115
• Paul Watkinsh-107
• Linda Adairh-106