On January 27, the Boston Biomedical Research Institute (BBRI) convened a celebration to honor Dr. Noriaki Ikemoto upon his retirement after 42 years as a member of BBRI’s faculty.  In his opening remarks, the Director, Dr. Charles C. Emerson, summarized Dr. Ikemoto’s distinguished career at BBRI.  Dr. Emerson pointed out that Dr. Ikemoto’s research has always been an outstanding example of translational research by focusing on proteins that are frequent targets of genetic disorders or chronic diseases in order to elucidate their mechanism of action and to identify potential therapies.

Dr.Ikemoto discussing his research

Dr. Ikemoto then gave a scholarly overview of his research on excitation-contraction coupling in muscle.  His research has focused on the important question of how excitation by nerves at the neuromuscular junction is propagated into the muscle cell to initiate contraction. This process involves a membrane system, the sarcoplasmic reticulum, and stimulates a protein called the ryanodine receptor (RyR), to open a calcium channel, causing muscle contraction. Abnormally regulated calcium signaling leads to skeletal muscle disease, such as malignant hyperthermia, and cardiac muscle disease, such as arrhythmogenic ventricular cardiomyopathy and stress-induced polymorphic ventricular tachycardia, two potentially fatal inherited cardiomyopathies. Dr. Ikemoto’s studies have led to the identification of a ‘domain-switch’ as a key mechanism for calcium channel regulation. Importantly, many mutations causing these diseases occur within the domain switch of RyR, indicating that the domain switch is an important site, not only to understand the basic mechanism of channel activation but also to understand the mechanism of pathogenesis. Since mutations in the domain switch produce severe aberrations of channel function in both skeletal and cardiac muscles, the domain switch is a good target for the development of therapeutic agents. For example, Dr. Ikemoto found that dantrolene, a drug commonly used to treat malignant hyperthermia, in fact binds to the domain switch and stabilizes the zipped configuration, preventing unwanted domain unzipping caused by disease conditions. He also discovered that a new chemical compound, JTV519, also prevents abnormal unzipping of the domain switch of cardiac RyR and the subsequent calcium leak that leads to cardiomyopathy.

After Dr. Ikemoto’s presentation, Drs. Albert Wang and Toshio Kitazawa read letters of appreciation from many colleagues and former coworkers and showed photographs spanning Dr. Ikemoto’s research career as well as many pleasant social occasions.  This was followed by remarks from many well-wishers, including members of BBRI’s Faculty and Board of Trustees as well as former colleagues.  The celebration closed with the presentation of a gift to Dr. Ikemoto to commemorate his important contribution to the Institute and a festive lunch.

Dr. Ikemoto receives best wishes on his retirement and a standing ovation from faculty, staff, trustees, and guests.