Hajime Tei

Scientific contributions

Chronobiology

Discovery of mammalian Period genes

In 1997, Hajime Tei, Yoshiyuki Sakaki, and Hitoshi Okamura identified the human and mouse Per homologues of the Drosophila Per gene. 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. 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. 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.

Identification of mammalian Timeless homolog

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

Discovery of circadian clocks in peripheral organs

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. In 2000, using their rodent model, they discovered the existence of circadian clocks in peripheral organs of mammals. This discovery led to the current understanding of mammalian circadian control as a multi-oscillatory system. He was also part of a team that discovered feeding cycles can entrain liver independently of the suprachiasmatic nucleus (SCN) and the light cycle.

Calcium flux in mammalian pacemaker neurons

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. 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.

Regulation of bone resorption by circadian clocks

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. Specifically for Bmal1, they found that Bmal1-deficient osteoblasts promote osteoclastogenesis. These findings could lead to future studies of RAR patterns and bone turnover markers.

Timeline of contributions

Applications of scientific contributions

Tei holds a patent on a Per1 promoter sequence that, when operably linked to another gene, will rhythmically promote its transcription. This promoter sequence allows for the creation of transgenic animals that will be useful in studying circadian disorders and diseases. Additionally, pharmaceutical treatments for such diseases can be tested on transgenic animals with this specific promoter.

Collaborators

From early in his professional career to his work current projects, Tei has worked with many other chronobiologists. Specifically, he is listed as a recurring co-author with the following scientists:

• Yoshiyuki Sakaki
• Shin Yamazaki
• Gene D. Block
• Rika Numano
• Michael Menaker