RESEARCH

INTEGRATIVE RESEARCH ON GPCRS AND THEIR SPECIFIC LIGANDS TO EXAMINE CELL SIGNALING AND PHYSIOLOGY

G-protein binding receptor (GPCR) is one of the most evolutionarily diversified superfamilies in human genomes and is important for a variety of physiological functions inside the human body. GPCR is thus the most significant protein in the drug research and development process, since 30% of FDA-approved medications target GPCR. From atomic-level investigation of ligand-receptor interactions to in-vivo research, our group investigates all aspects of GPCR architectures and functions. In addition, our lab intends to find and create new regulatory ligands—small chemical probes or tool compounds—to determine whether a particular GPCR is appropriate as a target receptor for in-vitro and in-vivo drug development. In order to achieve our objectives, our lab employs numerous methods and technologies to screen the entire GPCR-ome via a massive parallel screening campaign, including BRET assay, functional assay, radioligand binding assay, computational docking, medical chemistry, and analog search, among others. Our laboratory focuses on receptors that are essential for neuronal function and reproduction.

ORPHAN GPCR PROBE CREATION FOR ELUCIDATING UNIQUE PHYSIOLOGICAL MECHANISM

G protein-coupled receptors (GPCRs) without known endogenous ligands are referred to as "Orphan" or "Understudied" GPCRs. Information on disease-causing mutations in people and animal research have increased the need for the physiological significance of orphan GPCRs despite the lack of knowledge on their ligands. Our team uses a wide variety of approaches, including biochemistry, high-throughput screening, medicinal chemistry, computational biology, and structure-based drug design, to find novel physiological pathways and identify ligands of orphan GPCRs.

SYNTHETIC BIOLOGY-BASED CHEMOGENETIC PLATFORM TECHNOLOGY DEVELOPMENT FOR IN VIVO GPCR INVESTIGATION

Chemogenetics is a technique that affects brain function by manipulating electrical impulses in brain cells using low molecular weight substances, and it is one of the most valuable technologies for elucidating nerve function. In particular, this method is founded on the premise of altering GPCR, ion-channel, etc. to react to inert synthetic substances otherwise, producing these manufactured proteins in selected neurons, and using these compounds to regulate the behavior of animals. GPCR-based Designer Receptors Exclusively Activated by Designer Drugs (DREADD) technology is the most popular among them. Due to the compound's ability to cross the blood-brain barrier, current DREADD technology has been utilized primarily to investigate central neurons. However, when applied to peripheral neurons outside of the brain, it has demonstrated its limits by creating undesired side effects. Through the development of a novel low-molecular chemical that cannot cross the Blood-Brain Barrier and a new GPCR-based mutation that boosts its responsiveness, our group hopes to create a new DREADD technology that can be employed exclusively in peripheral neurons. It is anticipated that the technology will play a significant role in the research of the physiological impacts and concomitant disorders of the peripheral nervous system (e.g., pain and sensory abnormalities).