Overview
We are interested in the molecular mechanisms underlying chemosensation (taste and smell) in mammals. The receptors that detect odorants, pheromones, and many tastants including bitter and sweet chemicals are G-protein coupled receptors (GPCRs), which typically have seven transmembrane domains. There are many important questions that are still unanswered in chemosensory neurobiology. How do tens of thousands of different chemicals (tastants, odorants, or pheromones) interact with more than one thousand chemosensory receptors (about 1000 odorant receptors, 40 taste receptors and 200 vomeronasal receptors in the case of mice or rats)? How is the information coded in sensory cells and in the brain? How does the brain direct appropriate behavioral responses? What are the mechanisms underlying development and regeneration of sensory cells and specific synapse connections? We address these questions using molecular biology, genome information and genetics.
The detection of tastants is mediated by taste receptor cells that are clustered in taste buds in the mouth. Interestingly, some people can taste certain chemicals, such as 6-n-propylthiouracil (a bitter compound) while others can't. Likewise, some strains of mice can taste certain bitter or sweet tastants while others can't. Based on these variations, the bitter and sweet taste loci have been mapped on human or mouse chromosomes. By using the increasingly powerful genome informatics tools, we as well as other groups, have identified families of GPCRs that may detect bitter and sweet compounds. We seek to understand how specific changes in nucleotide sequences cause these differences in taste sensitivity. Another goal is to understand how the gustatory system is organized.
In olfaction, the detection of volatile odorants is mediated by olfactory sensory neurons in the olfactory epithelium of the nose. Odorants are detected by about 1000 different types of odorant receptors that are encoded by a multigene family. Each olfactory sensory neuron expresses only one receptor type out of 1000 receptors. Axons of neurons expressing the same receptor all converge in a few glomeruli in the olfactory bulb of the brain. We wish to understand the mechanisms underlying this convergence.
Finally, we are interested in the pheromone sensing system. Pheromones are chemicals that are released from animals and induce innate behavior, such as mating or aggression, or hormonal changes in members of the same species.
The detection of pheromones is mediated primarily by a second olfactory sense organ, called the vomeronasal organ (VNO). We, as well as other groups, have found families of candidate pheromone receptors by comparing gene expression between single VNO neurons. Pheromone molecules may induce their effects by activating some of these receptors, which ultimately affect particular regions of the brain. We seek to understand how these pheromonal effects are mediated.
The detection of tastants is mediated by taste receptor cells that are clustered in taste buds in the mouth. Interestingly, some people can taste certain chemicals, such as 6-n-propylthiouracil (a bitter compound) while others can't. Likewise, some strains of mice can taste certain bitter or sweet tastants while others can't. Based on these variations, the bitter and sweet taste loci have been mapped on human or mouse chromosomes. By using the increasingly powerful genome informatics tools, we as well as other groups, have identified families of GPCRs that may detect bitter and sweet compounds. We seek to understand how specific changes in nucleotide sequences cause these differences in taste sensitivity. Another goal is to understand how the gustatory system is organized.
In olfaction, the detection of volatile odorants is mediated by olfactory sensory neurons in the olfactory epithelium of the nose. Odorants are detected by about 1000 different types of odorant receptors that are encoded by a multigene family. Each olfactory sensory neuron expresses only one receptor type out of 1000 receptors. Axons of neurons expressing the same receptor all converge in a few glomeruli in the olfactory bulb of the brain. We wish to understand the mechanisms underlying this convergence.
Finally, we are interested in the pheromone sensing system. Pheromones are chemicals that are released from animals and induce innate behavior, such as mating or aggression, or hormonal changes in members of the same species.
The detection of pheromones is mediated primarily by a second olfactory sense organ, called the vomeronasal organ (VNO). We, as well as other groups, have found families of candidate pheromone receptors by comparing gene expression between single VNO neurons. Pheromone molecules may induce their effects by activating some of these receptors, which ultimately affect particular regions of the brain. We seek to understand how these pheromonal effects are mediated.
Current Appointments & Affiliations
Professor of Molecular Genetics and Microbiology
·
2015 - Present
Molecular Genetics and Microbiology,
Basic Science Departments
Professor of Neurobiology
·
2015 - Present
Neurobiology,
Basic Science Departments
Member of the Duke Cancer Institute
·
2001 - Present
Duke Cancer Institute,
Institutes and Centers
Faculty Network Member of the Duke Institute for Brain Sciences
·
2011 - Present
Duke Institute for Brain Sciences,
University Institutes and Centers
Professor of Cell Biology
·
2022 - Present
Cell Biology,
Basic Science Departments
Associate of the Duke Initiative for Science & Society
·
2017 - Present
Duke Science & Society,
University Initiatives & Academic Support Units
Recent Publications
An odorant receptor for a key odor constituent of ambergris.
Journal Article Commun Biol · May 23, 2025 Ambergris, a substance derived from the digestive system of sperm whales, has been valued for centuries for its unique aromatic properties. However, historical accounts indicate that certain human populations, particularly in East Asia, utilized ambergris ... Full text Link to item CiteAntagonists Enhance Cell-Surface Expression of Mammalian Odorant Receptors.
Journal Article Int J Mol Sci · February 10, 2025 Functional characterization of vertebrate odorant receptors (ORs), members of the G protein-coupled receptor (GPCR) family, is essential for understanding olfaction. However, the functional expression of ORs in heterologous cells is often challenging, at l ... Full text Link to item CitePatients with Wilson's Disease Are Insensitive to Sulfur Odors.
Journal Article Mov Disord Clin Pract · January 2025 Full text Link to item CiteRecent Grants
Mechanisms of Odor Detection and Discrimination
ResearchPrincipal Investigator · Awarded by National Institutes of Health · 2025 - 2030Neurobiology Training Program
Inst. Training Prgm or CMEMentor · Awarded by National Institutes of Health · 2024 - 2029STRUCTURAL DYNAMICS IN HUMAN ODORANT RECEPTOR FUNCTION
ResearchPrincipal Investigator · Awarded by University of California - San Francisco · 2023 - 2028View All Grants
Education, Training & Certifications
Kyoto University (Japan) ·
1996
Ph.D.