About

Henrik Gunnar Dohlman, PhD, is the Sanford Steelman Distinguished Professor and Chair of Pharmacology at the University of North Carolina at Chapel Hill. He received his PhD under the mentorship of 2012 Nobel Laureate Bob Lefkowitz at a nearby rival university. Following his doctoral studies, Henrik completed postdoctoral training with Jeremy Thorner at the University of California, Berkeley. In 1993, he became a professor of pharmacology at Yale University before relocating to UNC in 2001.

Research topics

• Cell biology
• Biology
• Biochemistry
• Computational biology
• Biophysics
• Genetics

Selected publications

• Scope evolution at the journal of biological chemistry: Advancing molecular insight in a changing scientific landscape

  Journal of Biological Chemistry · 2026-04-24

  articleOpen access1st authorCorresponding

  For more than a century, the Journal of Biological Chemistry has served as a home for rigorous, mechanistic studies that define our understanding of biological processes. This commitment to molecular and biochemical insight remains the foundation of the journal.

  PublisherOA PDFDOI

• Determinants of drug efficacy and the dynamics of G protein activation

  Nature Structural & Molecular Biology · 2026-04-30

  article1st authorCorresponding
  PublisherDOI

• Phosphorylation-activated G protein signaling stabilizes TCP14 and JAZ3 to repress JA signaling and enhance plant immunity

  Molecular Plant · 2025-06-12 · 10 citations

  articleOpen access
  PublisherOA PDFDOI

• Non-redundant roles for paralogous proteins in the yeast glucose-sensing pathway

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-07 · 1 citations

  preprintOpen accessSenior authorCorresponding

  , approximately one-fifth of the genome consists of paralogs, with their encoded proteins involved in multiple pathways. However, the unique contributions of individual paralogs have remained poorly defined. Here, we undertook a systematic examination of eight paralog pairs in the glucose-sensing pathways, deleting each component and measuring the resulting changes in gene expression. To that end we established a new transcription reporter system to monitor the response to glucose as well as to non-preferred sugars in single cells. Focusing on the PKA catalytic subunits, comprised of the paralogs Tpk1 and Tpk3 as well as the isomorphic kinase Tpk2, we employed mass spectrometry to identify their contribution to cellular metabolism, used a GFP-based sensor to follow changes in cytosolic pH, and used BioID to identify unique and shared binding partners. Our data reveal that paralogs in the glucose-sensing pathway contribute in multiple and unique ways to signal transduction, and establish potential mechanisms driving the preservation of these and other duplicated genes throughout long periods of evolution.

  PublisherOA PDFDOI

• Molecular and functional profiling of Gαi as an intracellular pH sensor

  Nature Communications · 2025-04-11 · 2 citations

  articleOpen access

  Heterotrimeric G proteins (Gα, Gβ and Gγ) act downstream of G-protein-coupled receptors (GPCRs) to mediate signaling pathways that regulate various physiological processes and human disease conditions. While human Gαi and its yeast homolog Gpa1 were previously postulated to function as intracellular pH sensors, the pH-sensing capabilities of Gαi and the underlying mechanism remain to be established. Our research shows that variations in pH significantly affect the structure and stability of Gαi-GDP. Specifically, at the lower end of the physiological pH range, the protein undergoes an order-to-disorder transition due to the loss of electrostatic interactions within the Gαi Switch regions, resulting in a reduction in agonist-mediated Gαi-Gβγ release. Further, we identified key residues within the Gαi Switch regions that form the pH-sensing network. Mutation of these residues in Gαi gives rise to 'low pH mimetics' that abolish pH-dependent thermostability changes and reduce Gαi-Gβγ release. Overall, our findings suggest that pH-sensitive structural changes in Gαi impact the agonist-mediated dissociation of Gβγ, which is essential for proper signaling.

  PublisherDOI

• Nonredundant roles for paralogous proteins in the yeast glucose-sensing pathway

  Molecular Biology of the Cell · 2025-12-16

  articleOpen accessSenior author

  , approximately one-fifth of the genome consists of paralogs, with their encoded proteins involved in multiple pathways. However, the unique contributions of individual paralogs have remained poorly defined. Here, we undertook a systematic examination of eight paralog pairs in the glucose-sensing pathways, deleting each component and measuring the resulting changes in gene expression. To that end, we established a new transcription reporter system to monitor the response to glucose as well as to nonpreferred sugars in single cells. Focusing on the PKA catalytic subunits, comprised of the paralogs Tpk1 and Tpk3 as well as the isomorphic kinase Tpk2, we employed mass spectrometry to identify their contribution to cellular metabolism, used a GFP-based sensor to follow changes in cytosolic pH, and used BioID to identify unique and shared candidate binding partners. Our data reveal that paralogs in the glucose-sensing pathway contribute in multiple and unique ways to signal transduction, and establish potential mechanisms driving the preservation of these and other duplicated genes throughout long periods of evolution.

  PublisherOA PDFDOI

• A neurodevelopmental disorder mutation locks G proteins in the transitory pre-activated state

  UNC Libraries · 2025-10-08

  articleOpen access
  PublisherDOI

• Shared and redundant proteins coordinate signal cross-talk between MAPK pathways in yeast

  Molecular Biology of the Cell · 2024-07-31 · 5 citations

  articleOpen accessSenior author

  All cells must detect, interpret, and adapt to multiple and concurrent stimuli. While signaling pathways are highly specialized, different pathways often share components or have components with overlapping functions. In the yeast Saccharomyces cerevisiae, the high osmolarity glycerol (HOG) pathway has two seemingly redundant branches, mediated by Sln1 and Sho1. Both branches are activated by osmotic pressure, leading to phosphorylation of the MAPKs Hog1 and Kss1. The mating pathway is activated by pheromone, leading to phosphorylation of the MAPKs Fus3 and Kss1. Given that Kss1 is shared by the two pathways, we investigated its role in signal coordination. We activated both pathways with a combination of salt and pheromone, in cells lacking the shared MAPK and in cells lacking either of the redundant branches of the HOG pathway. By systematically evaluating MAPK activation, translocation, and transcription programs, we determined that Sho1 mediates cross talk between the HOG and mating pathways and does so through Kss1. Further, we show that Kss1 initiates a transcriptional program that is distinct from that induced by Hog1 and Fus3. Our findings reveal how redundant and shared components coordinate concurrent signals and thereby adapt to sudden environmental changes.

  PublisherOA PDFDOI

• Abstract 2033 How G proteins work and what happens when they don't

  Journal of Biological Chemistry · 2024-03-01

  articleOpen access1st authorCorresponding

  Most hormones, neurotransmitters, and environmental signals, as well as a large proportion of all pharmaceuticals, exert their effects through G protein-coupled receptors. These receptors promote GTP binding to the G protein and dissociation of the constituent subunits. Receptor action is opposed by regulators of G protein signaling, which accelerate GTP hydrolysis. This cycle of G protein activation and inactivation has been extensively characterized using biochemical, cellular, and structural approaches. Complementing these efforts, much has been learned through molecular analysis of G protein mutants responsible for cancer as well as movement, endocrine and developmental disorders. Most prominently, these are uveal melanoma (affecting Gq) and developmental epileptic encephalopathy (affecting Gq). Whereas some disease mutations lock the G protein in either the apo, GTP- or GDP-bound states, others block association with GTPase-activating proteins or prevent dissociation of the G protein subunits. Mechanistic evaluation of these mutants has yielded a powerful and well-validated molecular toolkit for investigating – structurally and functionally - individual steps of the G protein activation cycle, and are likely to accelerate drug screening efforts in the years ahead. NIH R35GM118105.

  PublisherOA PDFDOI

• A universal allosteric mechanism for G protein activation

  Carolina Digital Repository (University of North Carolina at Chapel Hill) · 2024-07-27

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

Recent grants

• NIH Grant R01GM073180

  NIH · $2.6M · 2013

• NIH Grant R01GM080739

  NIH · $2.6M · 2015

• G protein regulation by monoubiquitination

  NIH · $1.1M · 2013–2017

• NIH Grant R01GM055316

  NIH · $1.1M · 2005

• NIH Grant R29GM055316

  NIH · $545k · 2001

Frequent coauthors

• Robert J. Lefkowitz

  39 shared

• Marc G. Caron

  Duke University Hospital

  37 shared

• Timothy C. Elston

  University of North Carolina at Chapel Hill

  36 shared

• Yuqi Wang

  Tianjin University

  33 shared

• Vera Bianchi

  University of Padua

  33 shared

• Roger Colbran

  33 shared

• George Demartino

  The University of Texas Southwestern Medical Center

  32 shared

• Erin Connolly

  Mitchell Institute

  31 shared

Labs

• Dohlman LabPI

Education

• PhD, Biochemistry

  Duke University Graduate School

  1988

• BA, Chemistry

  Wesleyan University

  1982