Department of Global Healthcare

 

TWITTER

https://twitter.com/Jose_Lab_QU

 

FACEBOOK

https://www.facebook.com/Jose-Lab-at-Kyushu-University-100839496037641

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


MEMBERS

Faculty

Professor: CAAVEIRO Jose, Ph.D.

(jose@phar.kyushu-u.ac.jp)

Junior Associate Professor: YANAKA Saeko, Ph.D.

           (saeko-yanaka@phar.kyushu-u.ac.jp)

Assistant Professor: YAMASHITA Tomohiro, Ph.D.

           (yamashita@phar.kyushu-u.ac.jp)

Assistant Professor: SENOO Akinobu, Ph.D.

           (senoo@phar.kyushu-u.ac.jp)

 

Graduate Students

INOUE Mao, D1

SHIOMI Toshiki, M1

YASUDA Tomonori, M1

YOSHINAGA Haruya, M1

 

Undergraduate Students

KOSEKI Yuuki, B4

YAWATA Kazuma, B4

NISHIMUTA Hiro, B4

TAGAWA Jumpei, B4

KAZAHAYA Yugo, B4

MORIKAWA Seiya, B3

YAMAMOTO Kota, B3

SEKI Kanta, B3

FUJISHIMA Kaiji, B3

SHIMOMURA Shoei, B3

 

 

 

研究概要

蛋白質工学と相互作用解析に基づく医薬品開発

生命現象の根底には蛋白質を始めとする生体分子間の相互作用が必ず存在しています。疾患関連蛋白質の相互作用を理解することは疾患メカニズムを理解することに直結し、同様に、その相互作用に対する制御分子の開発は医薬品の開発に直結します。当研究室では、高度な分子間相互作用測定技術を駆使して癌・炎症性疾患・感染症等に関わる生体分子間相互作用への理解を深めるとともに、その相互作用を制御可能な分子種の開発を行っています。そうした「分子種」の代表例として低分子化合物・ペプチド・抗体が挙げられます。当研究室ではそれらに加え、蛋白質工学の技術を最大限に活用し、画期的な創薬モダリティをデザインすることも目指します。今年度からは、グリーンファルマ構造解析センターとの連携により、細胞膜貫通蛋白質を始めとする高難度標的に対しても最先端の研究を展開していきます。

 

Research summary

The laboratory of Global Healthcare consolidates the international standing of the School of Pharmaceutical Sciences, and catalyzes the emergence of next-generation students with a deeper understanding of global issues. We study various diseases and maladies of widespread prevalence across the world, such as chronic pain, neurodegenerative diseases, cancer, and infectious diseases. Moreover, we investigate, design, and develop the future generation of pharmaceutical products to combat human disease and suffering. These products include not only novel chemical compounds and drugs, but also new modalities of antibodies as well as original vaccination strategies. We employ state-of-the-art molecular and structural technologies to understand the basic principles of disease, which are used as the basis to elaborate novel therapeutic solutions.

 

 

 

 

Address

Department of Global Healthcare

Graduate School of Pharmaceutical Sciences

Kyushu University

3-1-1 Maidashi, Higashi-ku, Fukuoka-shi, 812-8582

Japan

 

Publications

- Takahashi et al. (2022) Ca2+-induced structural changes and intramolecular interactions in N-terminal region of diacylglycerol kinase alpha. Protein. Sci. 31:e4365.

- Valenciano-Bellido, et al. (2022) Structure and role of the linker domain of the iron surface-determinant protein IsdH in heme transportation in Staphylococcus aureus. J. Biol. Chem. 298:101995.

- Yokoo et al. (2022) Antibody recognition of complement Factor H reveals a flexible loop involved in Atypical Hemolytic Uremic Syndrome pathogenesis. J. Biol. Chem. 298:101962.

- Takahashi et al. (2022) Compound screening identified gossypetin and isoquercitrin as novel inhibitors for amyloid fibril formations of V6 proteins associated with AL amyloidosis. Biochem. Biophys. Res. Commun. 596:22.

- Queliconi et al. (2021) Destabilization-triggered mitochondrial import and degradation of cytosolic protein DJ-1. J. Cell Sci. 134:jcs258653.

- Rujas et al. (2021) Focal accumulation of aromaticity at the CDRH3 loop mitigates 4E10 polyreactivity without altering its HIV neutralization profile. iScience 24:102987.

- Akiba et al. (2021) Epitope-dependent thermodynamic signature of single-domain antibodies against hen egg lysozyme. J. Biochem. 170:623.

- Yui et al. (2021) Mechanism of dimerization and structural features of human LI-cadherin. J. Biol. Chem. 297:101054.

- Oyama et al. (2021) Abolition of aggregation of CH2 domain of human IgG1 when combining glycosylation and protein stabilization. Biochem. Biophys. Res. Commun. 558:114.

- Oyama et al. (2021) High-level expression of human CH2 domain from the Fc region in Pichia pastoris and preparation of anti-CH2 antibodies. J. Biochem. 170:289.

- Maenaka et al. (2021) Viral Biophysics: Contributions to Drug Discovery Modalities. Seibutsu butsuri 61:2.

- Caaveiro and Tsumoto (2021) Molecular basis for the activation of actinoporins by lipids. Methods Enzymol. 469:277.

- Yamashita et al. (2021) New Inhibitory Effects of Cilnidipine on Microglial P2X7 Receptors and IL-1. Cells 10:434.

- Ishii et al. (2020) Structural Basis for Antigen Recognition by Methylated Lysine Specific Antibodies. J. Biol. Chem. 296:100176.

- Rujas et al. (2020) Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments. Cell Rep. 32:108037.

- Akiba et al. (2020) Computer-guided library generation applied to the optimization of single-domain antibodies. Prot. Eng. Des. Select. 32:423-31.

- Akiba et al. (2019) Structural and thermodynamic basis for the recognition of the substrate-binding cleft on hen egg lysozyme by a single-domain antibody. Sci. Rep. 9:15481.

- Morante et al. (2019) The isolation of new pore-forming toxins from the sea anemone Actinia fragacea provides insights into the mechanisms of actinoporin evolution. Toxins 11:E401.

- Igawa et al. (2019) Evidence for detection of rat P2X4 receptor expressed on cells by generating monoclonal antibodies recognizing the native structure. Purinergic signal. 15:27-39.

- Yamamoto et al. (2019) New pharmacological effect of fulvestrant to prevent oxaliplatin-induced peripheral neuropathy in rats. Int. J. Cancer Res. 145:2107–2113.

- Shindo et al. (2019) Selective and reversible covalent modification of non-catalytic cysteines with weakly reactive α-chlorofluoroacetamides. Nat. Chem. Biol., 15:250-258.

- Tashiro et al. (2018) Discovery and optimization of potent inhibitors of the Parkinson’s disease associated protein DJ-1. ACS Chem. Biol. 13:2783–2789.

- Yamashita et al. (2018) Green Pharma: A New Strategy for Drug Discovery in Academia by Targeting Glial Cells and ATP Receptors. Yakugaku Zasshi 138:1027-1031 (article in Japanese).

- Nagatoishi et al. (2018) Biophysical analysis of protein-small molecule interactions to develop small molecule drugs. Yakugaku Zasshi 138:1033-1041 (article in Japanese).

- Caaveiro et al. (2018) Heme-acquisition in Staphylococcus aureus by the iron-regulated surface determinant (Isd) system. Seikagaku 90:279-289, (article in Japanese).

- Miyanabe aet al. (2018) Intramolecular H-bonds govern the recognition of a flexible peptide by an antibody. Biochemistry 57:4177–4185.

- Tashima, et al. (2018) Weak electrostatic interactions between collagen and monomeric SLRP osteomodulin govern the shape of type I collagen fibrils. Commun. Biol. 1:33.

- Miyanabe et al. (2018) Intramolecular H-bonds govern the recognition of a flexible peptide by an antibody. J. Biochem. DOI:10.1093/jb/mvy032

- Kiyoshi et al. (2018) Assessing the heterogeneity of the Fc-glycan of a therapeutic antibody using an engineered FcγReceptor IIIa-immobilized column. Sci. Rep. 8:3955.

- Kiyoshi et al. (2017) Glycosylation of IgG-Fc: a molecular perspective. Int. Immunol. 29:311-317.

- Tanaka et al. (2017) Haemolytic actinoporins interact with carbohydrates using their lipid-binding module. Philos. Trans. R. Soc. Lond. B Biol. Sci., 372: 20160216.

- Rujas et al. (2017) Functional contacts between MPER and the anti-HIV-1 broadly neutralizing antibody 4E10 extend into the core of the membrane. J. Mol. Biol., 429:1213–1226.

- Rujas, et al. (2017) Peripheral membrane interactions boost the engagement by an anti HIV-1 broadly neutralizing antibody. J. Biol. Chem. 292:5571–5583.

- Kudo et al (2017) Disruption of cell adhesion by an antibody targeting the cell-adhesive intermediate (X-dimer) of human P-cadherin. Sci. Rep. 7:39518.

- Yamashita et al. (2016) Duloxetine inhibits microglial P2X4 receptor function and alleviates neuropathic pain after peripheral nerve injury. PLoS One, 11: e0165189.

- Rujas et al. (2016) Structural basis for broad neutralization of HIV-1 through the molecular recognition of 10E8 helical epitope at the membrane interface. Sci. Rep. 6:38177.

- Kudo et al. (2016) Adhesive dimerization of human P-cadherin catalyzed by a chaperone-like mechanism. Structure, 24:1523-1536.

- Matsumura et al. (2016) A novel P2X4 receptor-selective antagonist produces anti-allodynic effect in a mouse model of herpetic pain. Sci Rep. 6:32461.

- Morante et al. (2016) Identification of a membrane-bound prepore species clarifies the lytic mechanism of actinoporins. J. Biol. Chem. 291:19210-19219.

- Caaveiro et al. (2015) Structural analysis of Fc/FcγR complexes: a blueprint for antibody design. Immunol. Rev. 268:201-221.

- Kiyoshi et al. (2015) Structural basis for binding of human IgG1 to its high-affinity human receptor FcγRI. Nat. Commun. 6:6866.

- Tanaka et al. (2015) Structural basis for self-assembly of a cytolytic pore lined by protein and lipid. Nat. Commun. 6:6337.