Hiroaki Matsunami

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Hiroaki Matsunami Research Interest

 

 

 

My research program focuses on elucidating the molecular, structural, and systems-level mechanisms by which odorant receptors (ORs) encode chemical information and shape sensory perception. ORs represent the largest gene family and constitute an exceptional model for understanding how sequence diversity, structural dynamics, and cellular context converge to produce sensory outputs. Building on foundational work that enabled heterologous expression and high-throughput functional characterization of ORs, my current research aims to integrate structural biology, functional genomics, and neural circuit analysis to achieve a predictive understanding of olfaction.

 

 

 

A major current focus of my laboratory is the structural basis of odor recognition and receptor activation. Recent advances in GPCR structural biology, including atomic-level structures of mammalian ORs, have opened the possibility of defining how chemically diverse odorants interact with highly divergent receptor binding pockets. We seek to determine how receptor conformational dynamics govern ligand specificity, efficacy, and antagonism, and how these properties contribute to combinatorial odor coding. By combining cryo-EM, protein engineering, and computational modeling, we aim to establish principles of OR ligand recognition.

 

 

 

A second major direction involves understanding functional diversity and evolution of OR repertoires across species and individuals. OR genes undergo rapid evolutionary change, yet functional constraints shape receptor tuning and sensory capabilities. My lab investigates how sequence variation alters receptor function and how this variation contributes to species-specific ecological adaptation and human perceptual diversity. These studies provide insight into the genetic and molecular bases of sensory individuality and offer a framework for linking genotype to perceptual phenotype.

 

 

 

We are also pursuing a systems-level understanding of olfactory coding through in vivo functional genomics and neural mapping approaches. By leveraging sequencing–based strategies to identify receptor activation patterns during natural behaviors, we aim to connect receptor-level biophysics to neural representation and perceptual outcomes. This integrative approach seeks to bridge molecular and circuit-level descriptions of sensory processing, advancing our understanding of odor detection and discrimination.

 

 

 

Finally, an emerging goal of my research program is to explore broader biological roles of ORs beyond canonical olfaction, including their function in non-olfactory tissues and potential relevance to human health and disease. Understanding how these receptors are regulated, trafficked, and activated in diverse cellular environments may uncover novel physiological signaling pathways and therapeutic opportunities.

 

 

 

Through these efforts, my laboratory aims to advance our understanding of chemosensory GPCR biology, starting from descriptive catalogs of receptor–ligand relationships to predictive models of receptor function and sensory perception.