Hajime Tei

Born| March 1959
Nationality| Japanese
Known for| Chronobiology
Scientific career
Fields| Neurophysiology, general neuroscience, circadian rhythms, suprachiasmatic nucleus, clock gene
Institutions| Kanazawa University

Mitsubishi Kagaku Institute of Life Sciences

University of Tokyo

Hajime Tei (程 肇, テイ ハジメ born March 1959)[1][2] is a Japanese neuroscientist specializing in the study of chronobiology. He currently serves as a professor at the Kanazawa University Graduate School of Natural Science & Technology.[2] He is most notable for his contributions to the discovery of the mammalian period genes, which he discovered alongside Yoshiyuki Sakaki and Hitoshi Okamura.

## Contents

* 1 Career
* 1.1 Awards
* 2 Scientific contributions
* 2.1 Chronobiology
* 2.1.1 Discovery of mammalian Period genes
* 2.1.2 Identification of mammalian Timeless homolog
* 2.1.3 Discovery of circadian clocks in peripheral organs
* 2.1.4 Calcium flux in mammalian pacemaker neurons
* 2.1.5 Regulation of bone resorption by circadian clocks
* 2.2 Timeline of contributions
* 3 Applications of scientific contributions
* 4 Collaborators
* 5 References

## Career

Between 1991 and 1992, Tei was a fellow for the Fellowships of the Japan Society for Japanese Junior Scientists at the University of Tokyo’s Institute of Medical Science. He later held the position of assistant professor (1992-2001) and associate professor (2001-2004). During his time as an assistant professor, Tei worked alongside Yoshiyuki Sakaki and Hitoshi Okamura to discover the mammalian period genes Per1, Per2, and Per3. They also discovered the mammalian homolog of the Drosophila gene Timeless. In 2004, Tei became the principal investigator of the Laboratory of Chronogenomics at Mitsubishi Kagaku Institute of Life Sciences. In 2009, he became a full professor at the Kanazawa University Graduate School of Natural Science & Technology, a position he currently serves to-date.[2]

### Awards

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

## 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.[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]

#### Identification of mammalian Timeless homolog

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]

#### 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.[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]

#### 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.[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]

#### 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.[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]

### Timeline of contributions

Event  | Year

|

Discovery of mammalian Period genes  | 1997
Identification of mammalian Timeless homolog  | 1998
Discovery of circadian clocks in peripheral organs  | 2000
Study on calcium flux in mammalian pacemaker neurons  | 2005
Discovery of regulation of bone resorption by circadian clocks  | 2016

## 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.[13]

## 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:[14]

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

## References

1. ↑ Directory of Researchers at Kanazawa University
2. ↑ 2.0 2.1 2.2 Japan Science and Technology Agency. Researchmap,
3. ↑ "Circadian oscillation of a mammalian homologue of the Drosophila period gene". Nature 389 (6650): 512–6. October 1997. doi:10.1038/39086. PMID 9333243. Bibcode: 1997Natur.389..512T.
4. ↑ 4.0 4.1 4.2 "Temperature effect on entrainment, phase shifting, and amplitude of circadian clocks and its molecular bases". Chronobiology International 19 (5): 807–64. September 2002. doi:10.1081/CBI-120014569. PMID 12405549.
5. ↑ "Identification of the mammalian homologues of the Drosophila timeless gene, Timeless1". FEBS Letters 441 (3): 427–31. December 1998. doi:10.1016/S0014-5793(98)01597-X. PMID 9891984.
6. ↑ Inaguma, Yutaka; Ito, Hidenori; Hara, Akira; Iwamoto, Ikuko; Matsumoto, Ayumi; Yamagata, Takanori; Tabata, Hidenori; Nagata, Koh-ichi (March 2015). "Morphological characterization of mammalian Timeless in the mouse brain development". Neuroscience Research 92: 21–28. doi:10.1016/j.neures.2014.10.017. PMID 25448545.
7. ↑ 7.0 7.1 "The daily rhythms of genes, cells and organs. Biological clocks and circadian timing in cells". EMBO Reports 6 Spec No (Suppl 1): S9-13. July 2005. doi:10.1038/sj.embor.7400424. PMID 15995671.
8. ↑ "Advances in understanding the peripheral circadian clocks". FASEB Journal 26 (9): 3602–13. September 2012. doi:10.1096/fj.12-203554. PMID 22661008.
9. ↑ Fu, Minnie; Yang, Xiaoyong (15 August 2017). "The sweet tooth of the circadian clock". Biochemical Society Transactions 45 (4): 871–884. doi:10.1042/BST20160183. PMID 28673939.
10. ↑ 10.0 10.1 "Encoding the ins and outs of circadian pacemaking". Journal of Biological Rhythms 21 (6): 470–81. December 2006. doi:10.1177/0748730406294316. PMID 17107937.
11. ↑ Rogers, Tara S.; Harrison, Stephanie; Swanson, Christine; Cauley, Jane A.; Barrett-Connor, Elizabeth; Orwoll, Eric; Stone, Katie L.; Lane, Nancy E. (December 2017). "Rest-activity circadian rhythms and bone mineral density in elderly men". Bone Reports 7: 156–163. doi:10.1016/j.bonr.2017.11.001. PMID 29181439.
12. ↑ 12.0 12.1 Song, Chao; Wang, Jia; Kim, Brett; Lu, Chanyi; Zhang, Zheng; Liu, Huiyong; Kang, Honglei; Sun, Yunlong et al. (27 September 2018). "Insights into the Role of Circadian Rhythms in Bone Metabolism: A Promising Intervention Target?". BioMed Research International 2018: 9156478. doi:10.1155/2018/9156478. PMID 30363685.
13. ↑ "Hajime Tei Inventions, Patents and Patent Applications - Justia Patents Search". https://patents.justia.com/inventor/hajime-tei.
14. ↑ "Hajime Tei - Semantic Scholar". https://www.semanticscholar.org/author/Hajime-Tei/47329317.

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