About | BioSignal Protein Research Lab

Our lab aims to study biosignal proteins related to human diseases, under the leadership of our Principal Investigator (PI), Dr. Kozo Hamada. We will try to develop new biomedical approaches using biosignal protein engineering to address human diseases, including neurodegenerative disorders and cancer. For inquiries, you can email to Kozo.Hamada@xjtlu.edu.cn.

Research interests

Protein Engineering
Signal Transduction
Protein Biogenesis
Neurodegenerative Disease
Protein Plasticity
Brain Biochemistry
Protein Crystallography
Calcium Signaling

Mingjun Jiang
Yunjian Wu
Jiayu Yang
Xiaoyuan Shen
Yiying Li
Xinyi Li
Zhechen Zhu

SURF students
Yihe Zhang
Shu Wang
Sakinah Binti Ashok Nawaz (Taylor's Univ, Malaysia)

Biochemical Studies of Serotonin Neurotransmission in the Brain

The axons of serotonin-containing neurons located in the raphe nucleus of the brainstem project throughout the brain and regulate the entire brain. At the Department of Biomedical Chemistry of the University of Tokyo School of Medicine (Katsuji Takai Lab), our principal investigator (PI) contribute to develop a method for rapid and specific depletion of serotonin from the brain with  colleagues. This was a new method that involved administering tryptophan side chain oxidase (TSO) to remove the precursor, tryptophan. They successfully removed tryptophan in the blood to below 2% within two hours using TSO. Serotonin in the brain decreased by 30% within six hours, causing abnormalities in the sleep-wake cycle, and a new serotonin depletion method was established (Eur J Neurosci, 2012). Although brain activity is governed by a circadian rhythm of approximately 24 hours that is located in the suprachiasmatic nucleus, when serotonin was removed with TSO, the circadian rhythm of sleep-wake cycles disappeared while the suprachiasmatic nucleus's circadian rhythm remained intact. This suggests that serotonin plays a role in transmitting signals from the internal clock to the brain (J Neurosci, 2012).

Structural and Functional Studies of ER-resident calcium channel

Gene mutations of the inositol trisphosphate (IP3) receptor are the cause of familial spinocerebellar ataxia and Gillespie syndrome. The IP3 receptor also regulates endoplasmic reticulum (ER) stress (Neuron, 2010) and autophagy (Autophagy, 2016). Therefore, elucidating the mechanism of action of the IP3 receptor is expected to lead to the development of drugs for these diseases.

Our PI successfully expressed and crystallized a giant protein with 2,200 amino acids that connects the IP3 binding site to the channel site, and then analyzed its X-ray crystal structure (Hamada et al., PNAS, 2017). By determining the crystal structure of the presence and absence of IP3 and deletion mutants, followed by functional analysis through genetic manipulation, our PI elucidated a new gating mechanism. 

The IP3 receptor is a channel formed by the combination of four subunits that create a small ion pore that allows the passage of only one Ca2+ ion in the center (Hamada et al., Science Signaling, 2012). Our PI revealed that abnormal control of Ca2+ signaling and autophagy occurs when there are structural changes between the subunits (Hamada et al., PNAS, 2014). Based on abovementioned researches, our PI have proposed conformational plasticity of the endoplasmic reticulum (ER)-resident calcium channels involved in divergent functions (Hamada et al., Ann Rev Physiol, 2020).

Selected Publications (*corresponding author)

1. *Hamada et al. Ann Rev Physiol (2020) 82, 151-176
2. Hamada et al. PNAS (2017) 114 (18), 4661-4666
3. *Hamada et al. PNAS (2014) 111(38), E3966-75
4. *Miyamoto, Nakamaru, Hamada et al. J Neurosci (2012) 32(42), 14794-803
5. *Nakamaru, Miyamoto, Hamada, et al. Eur J Neurosci (2012) 35(11), 1762-70
6. *Hamada et al. Science Signaling (2012) 5(225), pe24
7. Higo, Hamada, et al. Neuron (2010) 68 (5), 865-78

Original Papers *corresponding author

1. Lavik AR, McColl KS, Lemos FO, Kerkhofs M, Zhong F, Harr M, Schlatzer D, Hamada K, et al. (2022) BBA Mol Cell Res 1869(4):119206 [IF = 5.0]
2. Rosa N, Ivanova H, Wagner LE 2nd, Kale J, La Rovere R, Welkenhuyzen K, Louros N, Karamanou S, Shabardina V, Lemmens I, Vandermarliere E, Hamada K, et al. (2022) Cell Death Differ 29(4):788-805. [IF = 12.1]
3. Kanda Y, Satoh R, Takasaki T, Tomimoto N, Tsuchiya K, Tsai CA, Tanaka T, Kyomoto S, Hamada K, Fujiwara T, Sugiura R. (2021) J Cell Sci 134(2):jcs250191. [IF = 5.2]
4. Yue L, Wang L, Du Y, Zhang W, Hamada K, et al. (2020) Cells 9(2):275. [IF = 7.7]
5. *Hamada K, et al. (2020) Annu Rev Physiol 82:151-176. [IF = 22.2]
6. Panizza E, Zhang L, Fontana JM, Hamada K, et al. (2019) FASEB J 33(9):10193-10206. [IF = 5.8]
7. Ivanova H, Wagner LE 2nd, Tanimura A, Vandermarliere E, Luyten T, Welkenhuyzen K, Alzayady KJ, Wang L, Hamada K et al. (2019) Cell Mol Life Sci 76(19):3843-3859. [IF = 9.2]
8. Hisatsune C, Hamada K, et al. (2018) BBA Mol Cell Res 1865:1733-1744. [IF = 5.0]
9. Hamada K, et al. (2017) PNAS 114(18), 4661-4666. [IF = 12.8]
10. *Klionsky DJ, (…), Hamada K , (…) et al. (2016) Autophagy 12(1), 1-222 [IF = 13.4]
11. *Hamada K, et al. (2014) PNAS 111(38), E3966-75 [IF = 12.8]
12. Nakamura K, Hamada K, et al. (2013) Cell Calcium 54(2), 111-9 [IF = 4.7]
13. Hudec R, Hamada K, et al. (2013) Anal Biochem 433(2), 95-10 [IF = 3.2]
14. *Hamada K et al. (2012) Science Signaling 5(225), pe24, [IF = 9.7 ]
15. *Miyamoto H, Nakamaru-Ogiso E, Hamada K, *Hensch TK (2012) J Neurosci 32(42), 14794-14803 [IF = 6.2]
16. *Nakamaru-Ogiso E, Miyamoto H, Hamada K, Tsukada K, Takai K (2012) Eur J Neurosci 35(11), 1762-70, 2012 [IF = 3.7]
17. Higo T, Hamada K, et al. (2010) Neuron 68(5), 865-78 [IF = 18.7]
18. Ozaki S, Ebisui E, Hamada K, et al. (2011) Bioorg Med Chem Lett 21(1), 377-9 [IF = 2.9]
19. Ozaki S, Ebisui E, Hamada K, et al. (2010) Bioorg Med Chem Lett 20(3), 1141-4 [IF = 2.9]
20. Suhara W, Kobayashi M, Sagara H, Hamada K, et al. (2006) Neurosci Lett 391(3), 102-7 [IF = 3.2]
21. Sato C, Hamada K, et al. (2004) J Mol Biol 336(1), 155-64 [IF = 6.2]
22. *Hamada K, et al. (2003) J Biol Chem 278(52), 52881-9 [IF = 5.5]
23. *Hirota J, Ando H, Hamada K, et al. (2003) Biochem J 372(Pt 2), 435-41 [IF = 3.8]
24. *Hamada K, et al. (2002) J Biol Chem 277(24), 21115-8 [IF = 5.5]

Conference Presentation

1. Hamada K Gordon Research Conference (USA) March 4th, 2018
2. Hamada K Gordon Research Conference (Italy) June 22th, 2017 [Late-Breaking Topics for oral presentation]
3. Hamada K Osaka University Protein Institute Seminar Aug 4th, 2017
4. Hamada K Annual Meeting of the Japan Neurochemistry Society　Sep 7th, 2017
5. Hamada K et al. Annual Meeting of the Japanese Society for Neurochemistry　Sep 11th, 2015
6. Hamada K JST ICORP Live (Tokyo)  2005 
7. Hamada K RIKEN/BBSRC Joint Symposim on Japan-UK Membrane Protein Structure Biology (RIKEN SPring8) 2003 
8. Hamada K ICORP/Karolinska Institute Intermediate Symposium (Karolinska Institute, Sweden) 2003 
9. Hamada K Annual meeting of the Biophysical Society of Japan  2003 
10. Hamada K Annual Meeting of the Japanese Society for Neurochemistry 2002 
11. Hamada K, et al. Annual Meeting of the Japan Neuroscience Society  1997 
12. Hamada K, et al. Annual Meeting of the Japanese Biochemical Society 1997 
13. Hamada K, et al. Annual Meeting of the Japanese Biochemical Society  1996 
14. Hamada K, et al. Annual Meeting of the Japanese Biochemical Society  1995 
15. Hamada K, et al. Annual Meeting of the Japanese Biochemical Society  1994 
16. Hamada K, et al. Annual Meeting of the Japanese Biochemical Society  1993 
17. Hamada K, et al. Annual Meeting of the Japanese Biochemical Society  1992 
18. Hamada K, et al. Annual Meeting of the Japanese Biochemical Society  1991