Hajime Tei

Hajime Tei received the 13th Tsukahara Memorial Award in 1999, and the Aschoff-Honma Prize for chronobiology in 2001.

In 1997, Hajime Tei, Yoshiyuki Sakaki, and Hitoshi Okamura identified the human and mouse Per homologues of the Drosophila Per gene.[3] They discovered that hPer (the human homolog of dPer) and mPer (the mouse homolog of dPer) encoded PAS-domain-containing polypeptides that are highly homologous to dPer.[4] They also found that mPer showed autonomous circadian oscillation in its expression in the suprachiasmatic nucleus (SCN) which acts as the primary circadian pacemaker in the mammalian brain.[4] They were able to discover this by using a method called intra-module scanning-polymerase chain reaction (IMS-PCR), which allowed them to screen out short stretches of DNA sequences and isolate mammalian homologs of the Drosophila Per gene.[4]

In 1998, Hajime Tei, in collaboration with other researchers, identified a mammalian homolog of the Drosophila timeless gene.[5] During this research project, timeless was analyzed in the adult mouse SCN, but only weak oscillations were observed.[6]

Tei and Shin Yamazaki developed the first rodent model that was used to monitor circadian gene expression rhythms. This was done using a luciferase reporter gene expressed under the Per1.[7] In 2000, using their rodent model, they discovered the existence of circadian clocks in peripheral organs of mammals.[7] This discovery led to the current understanding of mammalian circadian control as a multi-oscillatory system.[8] He was also part of a team that discovered feeding cycles can entrain liver independently of the suprachiasmatic nucleus (SCN) and the light cycle.[9]

In 2005, Tei, G. Lundkvist, Y. Kwak, E. Davis, and G. Block proposed that the molecular clock was linked to neurons' membrane potential via voltage-dependent regulation of Ca²⁺ influx, as well as secondary action of intracellular Ca²⁺ on gene transcription.[10] Additionally, the same study found that removal of Ca²⁺ from the medium, as well as blocking the Ca²⁺ channels, stopped the SCN's circadian clock, while hyperpolarization of a K⁺ medium led to altered rhythms in the SCN.[10]

In 2016, a research team that included Tei discovered that clock genes, most specifically Bmal1 and Per1, are rhythmically expressed in osteoblasts to modulate the osteoblast-dependent regulation of osteoclastogenesis by regulating 1,25(OH)₂D₃-induced Rankl expression in osteoblasts.[11] Specifically for Bmal1, they found that Bmal1-deficient osteoblasts promote osteoclastogenesis.[12] These findings could lead to future studies of RAR patterns and bone turnover markers.[12]