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“Analyzing movements and disease conditions of genetically-modified mice, aiming to find target molecules that can lead to new drug discoveries”
Akimichi Baba
Elucidation of totally new target molecules for drug discovery based on genetic information
For the past 15 years I have worked at Graduate School of Pharmaceutical Sciences, Osaka University, engaged in the field of neuropharmacology, aiming to elucidate the molecular basis for certain pathological conditions mainly by creating genetically-engineered mice and analyzing their movements and disease conditions for the purpose of clarifying the physio-pathological significance of neuropeptide PACAP. I have proved through various studies that the first successful PACAP gene knockout (PACAP-KO) mice in my laboratory are the new mouse model for schizophrenia, and that mutation in the PACAP gene is related to pathological conditions of this disorder also in humans. PACAP is thus an important signal that, if it has a mutation, can cause abnormalities in similar higher brain functions in mice and humans, and currently I am continuing studies to elucidate downstream target molecules that have a more direct relation with the abnormalities.
Further studies for discovery of new target molecules
On the other hand, through reverse pharmacological studies on the relation between pancreatic PACAP and diabetic pathological conditions of diabetes, I have clarified that PACAP suppresses hyperplasia of pancreatic islets in diabetics, and have extracted two new functional genes related to the suppression. One is an anti-inflammatory factor, and the other is a totally new factor that controls mitochondrial function. I am currently examining their physio-pathological functions, so that they can be utilized in finding new target molecules for drug discovery.
The PACAP-KO mouse, placed in a closed space, exhibited hyperactivity, including explosive jumping behavior. In addition, learning and memory disorders, state of depression, decline in sensory information filtering ability, and impaired photic entrainment of the biological clock were observed.
Clinical testing was conducted in collaboration with the department of psychiatry to verify the correlation between mutation in the PACAP gene and functional abnormalities in schizophrenic patients. As a result, it has been clarified that a certain kind of mutation in the PACAP gene is related to functional decline in hippocampus in human schizophrenia.
Researcher introduction
Akemichi Baba, Vice President, Professor of School of Pharmacy
Professor Baba finished Graduate School of Pharmaceutical Sciences, Osaka University, and later became a Professor of the same graduate school. Having served as a Trustee and Vice President of Osaka University, he became a Professor Emeritus, and assumed the current position in April, 2010. He received the Pharmaceutical Society of Japan Award in 2007. Professor Baba, who is also Vice Chairman of the Pharmaceutical Society of Japan and former President of the Japanese Pharmacological Society, specializes in neuropharmacology.