Primary Research Focus
The Masuho Lab studies molecular and cellular aspects of G protein-coupled receptor (GPCR) signaling. GPCRs are the largest class of cell surface receptors and are activated by a diverse range of extracellular stimuli, including hormones and neurotransmitters. They play crucial roles in cellular functions, such as chemotaxis and synaptic plasticity, and are involved in virtually all physiological processes.
As a system with much physiological importance, dysregulation in the GPCR signaling system has been implicated in a broad range of human disorders. These receptors are also the primary target of current therapeutic agents. Therefore, a precise understanding of the signaling pathways at the molecular and cellular levels is among the highest priorities of public health research.
This lab aims to interpret the molecular mechanisms and structural basis of how GPCR signaling molecules control broad cellular functions, identify the causes of diseases and apply these findings to medical treatment.
About the Masuho Lab
Lab Projects and News
Precision Medicine Targeting the GPCR Signaling Pathway
Understanding the molecular and cellular basis of diseases is for designing appropriate and effective treatments. Although recent exome studies have identified mutations in GPCR signaling molecules in patients spanning a wide range of diseases, the causality of the mutations is not established in many cases due to the limited number of patients, especially for rare and ultra-rare genetic disorders. Therefore, we perform functional studies of putative causative genes to establish the causality and the molecular mechanism of disease pathogenesis. Moreover, since genetic variations are involved in non-disease human traits, our laboratory examines the functional effects of non-pathogenic genetic variants of GPCR signaling molecules on drug-induced responses. Through these studies, we aim to deliver the right pharmacotherapy to the right patient.
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The Systems Biology of GPCR Signaling
For a deep understanding of complex GPCR signal transduction consisting of considerable numbers of signaling molecules and regulators, comprehensive and systematic approaches to directly quantitate enzymatic activities and determine the selectivity of protein-protein interactions in living cells are required. To tackle this challenge, we have employed a unique single platform assay capable of measuring the enzymatic activities of GPCRs, G proteins and RGS proteins in living cells. Using this assay together with other in cellulo assays, we research to reveal the principles and rules that dwell in the complex GPCR signaling system.
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The Mechanisms of Drug Actions on GPCRs
Despite the importance of GPCRs as drug targets, there are substantial challenges in understanding drug action mechanisms at these receptors. Understanding the detailed mechanisms of how drugs act on GPCRs would facilitate the development of more effective drugs with fewer side effects. Therefore, we conduct research to elucidate the molecular mechanism of how drugs control the function of GPCRs and consequently cellular functions, in hopes of realizing the effective development of better drugs.
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