Professor of Neurobiology
Member of the Duke Cancer Institute
Faculty Network Member of the Duke Institute for Brain Sciences
Associate of the Duke Initiative for Science & Society
We investigate how we detect and discriminate tens of thousands of odorous chemicals using hundreds of olfactory receptors encoded in the mammalian genome. We mainly use molecular genetics, cell biology, imaging and behavioral approaches in mice.
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.
Cong, Xiaojing, Wenwen Ren, Jody Pacalon, Rui Xu, Lun Xu, Xuewen Li, Claire A. de March, et al. “Large-Scale G Protein-Coupled Olfactory Receptor-Ligand Pairing.” Acs Cent Sci 8, no. 3 (March 23, 2022): 379–87. https://doi.org/10.1021/acscentsci.1c01495.
Ghosh, Soumadwip, Claire A. de March, Sergio Branciamore, Sahar Kaleem, Hiroaki Matsunami, and Nagarajan Vaidehi. “Sequence coevolution and structure stabilization modulate olfactory receptor expression.” Biophys J 121, no. 5 (March 1, 2022): 830–40. https://doi.org/10.1016/j.bpj.2022.01.015.
Oliva, Allison D., Rupali Gupta, Khalil Issa, Ralph Abi Hachem, David W. Jang, Sebastian A. Wellford, E Ashley Moseman, Hiroaki Matsunami, and Bradley J. Goldstein. “Aging-related olfactory loss is associated with olfactory stem cell transcriptional alterations in humans.” J Clin Invest 132, no. 4 (February 15, 2022). https://doi.org/10.1172/JCI155506.
Orecchioni, Marco, Kouji Kobiyama, Holger Winkels, Yanal Ghosheh, Sara McArdle, Zbigniew Mikulski, William B. Kiosses, et al. “Olfactory receptor 2 in vascular macrophages drives atherosclerosis by NLRP3-dependent IL-1 production.” Science 375, no. 6577 (January 14, 2022): 214–21. https://doi.org/10.1126/science.abg3067.
Vihani, Aashutosh, Maira Nagai, Conan Juan, Claire de March, Xiaoyang Hu, John Pearson, and Hiroaki Matsunami. “Encoding of odors by mammalian olfactory receptors,” December 28, 2021. https://doi.org/10.1101/2021.12.27.474279.
Fukutani, Yosuke, Yuko Nakamura, Nonoko Muto, Shunta Miyanaga, Reina Kanemaki, Kentaro Ikegami, Keiichi Noguchi, Ikuroh Ohsawa, Hiroaki Matsunami, and Masafumi Yohda. “Hot Spot Mutagenesis Improves the Functional Expression of Unique Mammalian Odorant Receptors.” Int J Mol Sci 23, no. 1 (December 28, 2021). https://doi.org/10.3390/ijms23010277.
Jabeen, Amara, Claire A. de March, Hiroaki Matsunami, and Shoba Ranganathan. “Machine Learning Assisted Approach for Finding Novel High Activity Agonists of Human Ectopic Olfactory Receptors.” Int J Mol Sci 22, no. 21 (October 26, 2021). https://doi.org/10.3390/ijms222111546.
Fukutani, Yosuke, Kentaro Ikegami, Masafumi Yohda, and Hiroaki Matsunami. “Improvement of the functional expression of mouse odorant receptors by site-directed mutagenesis based on RTP independency.” In Chemical Senses, Vol. 46, 2021.
March, Claire A. de, Kara C. Hoover, Masashi Abe, and Hiroaki Matsunami. “Smelling through old noses via genetic and functional variations in extinct human lineages.” In Chemical Senses, Vol. 46, 2021.
Abaffy, Tatjana, and Hiroaki Matsunami. “19-hydroxy Steroids in the Aromatase Reaction: Review on Expression and Potential Functions.” J Endocr Soc 5, no. 7 (July 1, 2021): bvab050. https://doi.org/10.1210/jendso/bvab050.