Hiroaki Matsunami, PhD – Biography
Hiroaki Matsunami earned his bachelor’s degree in Biology from Kyoto University in 1991. He went on to earn his master’s degree in 1993 and his Ph.D. in 1996 in Dr. Masatoshi Takeichi’s lab studying the role of cadherin cell adhesion molecules during brain development in mammals.
Dr. Matsunami completed his postdoctoral training in Dr. Linda Buck’s lab at Harvard University. There, he conducted a number of projects involving the identification of new mammalian chemosensory receptors. First, Dr. Matsunami identified a family of chemosensory receptors, V2Rs, which are expressed in the vomeronasal organ, a second olfactory organ implicated in detection of pheromones and other semiochemicals. Second, together with Dr. Jean-Pierre Montmayeur, he identified a family of bitter taste receptors, T2Rs. Drs. Linda Buck and Richard Axel were awarded the 2004 Nobel Prize in Physiology or Medicine. In her Nobel lecture, Dr. Buck mentioned his work and acknowledged his contributions.
In 2001, Dr. Matsunami moved to Duke University to start his own lab with the goal of deepening our understanding of molecular mechanisms underlying olfaction and other chemical senses.
As an assistant professor, Dr. Matsunami’s lab identified the RTP family of accessory proteins that induce functional expression of mammalian ORs in heterologous cells. This finding overcame a long-standing challenge in the field and promoted the establishment of a platform for high-throughput “deorphanization” of mammalian ORs. In collaboration, Dr. Matsunami demonstrated that functional variation of a human OR, OR7D4, affects odor perception of its cognate ligand androstenone. This was the first characterization of the genetic basis of a specific anosmia. In addition, Dr. Matsunami contributed to the identification of candidate sour taste receptors as well as an elucidation of CO2 detection in rodents.
As an associate professor, Dr. Matsunami’s group identified active ligands for over 50 mammalian ORs using a heterologous expression system that his lab developed. This was the first large-scale characterization of odorants-odorant receptor pairs in mammals. His group investigated functional evolution of OR orthologs in primates and rodents and demonstrated dynamic changes in responses between related species. His lab showed that OR7D4 affects the human preference for pork containing androstenone, the first demonstration that ORs contribute to food preference. To deepen our understanding of olfactory transduction, Dr. Matsunami’s lab showed the activation state of the M3 muscarinic acetylcholine receptor, a non-OR GPCR, modulates OR signaling. In collaboration, his group showed a crucial role of extracellular copper ion in OR activation by thiol odors, the first demonstration of metal ion involvement in OR function. His lab showed the role of calreticulin chaperones in preventing functional expression of V2R pheromone receptors outside the vomeronasal organ, where expression of calreticulin is sparse. This finding paved the way towards functional characterization of V2R members. Lastly, Dr. Matsunami’s lab found that the majority of human odorant receptors have genetic polymorphisms that alter function. On average, two individuals have functional differences at over 30% of their odorant receptor alleles. This unusually high level of functional variability in the primary receptors transducing olfactory information is strongly suggestive of high inter-individual variability in odor detection at the receptor level.
In summary, as an independent investigator, Dr. Matsunami made contributions in the field of chemical senses, first by establishing a method to functionally express mammalian ORs through the discovery of key accessory proteins. Using this as a platform, Dr. Matsunami’s lab identified a large number of active ligands for many ORs, characterized OR variants and determined contributions of ORs in odor perception and food preference, and found important roles that a non-OR GPCR as well as extracellular metal ions play in OR activation.
As a graduate student, Dr. Matsunami received a JSPS pre-doctoral fellowship. During his post-doctoral training period, he received a Naito Foundation and JSPS postdoctoral fellowships. As an assistant professor, Dr. Matsunami received a Human Frontier Science Program (HFSP) Young Investigator grant with Dr. Luo. Dr. Matsunami is an American Association for the Advancement of Science (AAAS) fellow. He serves as an academic editor for the journals PLoS One and PeerJ.