• To investigate formation mechanisms for highly integrated functions of differentiated cells such as endocrine cells and neuronal cells with use of molecular and cellular technical approaches.

• To invent luminescent probes for analyzing a membrane cholesterol composition, and for identifying a hypoxic region in a variety of pathological tissues such as cancers and infarcts.

• Mechanisms on secretory granule formation and secretion in endocrine cells such as pancreatic β-cells and pituitary cells. [Mol. Biol. Cell 13: 3388, 2002; J Biol Chem 279:3627, 2004; J Cell Sci 118:4785, 2005; Traffic 6:1213, 05; Curr Diabetes Rev 4:31, 2008 (review); Mol Endocrinol 22:1935, 2008; Endocr J. 57:275, 2010 (Review；Free PDF); Endocrinology 151, 4705-4716, 10; Traffic 14, 205-218, 13; J Histochem Cytochem 63, 350-356, 2015；Endocrinology 159, 1213-1227, 2018；J. Histochem. Cytochem. 69, 229-243, 2021]

• Development of hypoxia-specific luminescent probe for identifying cancers and infarcts. (Cancer Res. 70:4490,10 ; Angew Chem Int Ed Engl. 51, 4148-4151, 2012)S

• Development of subcellular organella-specific fluorescent probes that detect a cholesterol-rich domain in the membrane. (BBA Mol/Cell Biol Lipids 176:1639, 2006; Endocrinology 151, 4705-4716, 2010 )

• Oxygen-response in neuro-endocrine cells. （Biochemical Journal 476, 827-842, 2019）

Publications;
2022

• Gomi H., Nagumo T., Asano K., Konosu K., Yasui T., Torii S., Hosaka M.; Differential expression of secretogranin II and III in canine adrenal chromaffin cells and pheochromocytomas. J. Histochem. Cytochem. 70, 335-356

• Gomi H., Hinata A., Yasui A., Torii S., Hosaka M.; Expression Pattern of the LacZ Reporter in Secretogranin III Gene-trapped Mice. J. Histochem. Cytochem. 69, 229-243

• Sato E., Maeda Y., Sato Y., Hinata A., Gomi H., Koga D., Torii S., Watanabe T., Hosaka M.; Culture in 10% O2 enhances the production of active hormones in neuro-endocrine cells by up-regulating the expression of processing enzyme. Biochemical Journal 476, 827-842

• Torii S., Kubota C., Saito N., Kawano A., Hou N., Kobayashi M., Torii R., Hosaka M., Kitamura T., Takeuchi T., Gomi H.; The pseudophosphatase phogrin enables glucose-stimulated insulin signaling in pancreatic β-cells. J. Biol. Chem. 293, 5920-5933

• Maeda Y., Kudo S., Tsushima K., Sato E., Kubota C., Kayamori A., Bochimoto H., Koga D., Torii S., Gomi H., Watanabe T., Hosaka M.; Impaired processing of prohormones in secretogranin III null mice causes maladaptation to an inadequate diet and stress. Endocrinology 159, 1213-1227.

• Gomi H., Osawa H., Uno R., Yasui T., Hosaka M., Torii S., Tsukie A.; Canine Salivary glands; analysis of Raw and SNARE protein expression and SNARE complex formation with diverse tissue properties. J. Histochem Cytochem 65, 637-653.

• Yoshihara T., Hirakawa Y., Hosaka M., Nangaku M., Tobita S.; Oxygen imaging of living cells and tissues using luminescent molecular probes. Journal of Photochemistry and Photobiology C: Photochemistry Reviews. 30, 71-95

• Nakazawa N., Sato A., Hosaka M.; TORC1 activity is partially reduced under nitrogen starvation conditions in sake yeast Kyokai no. 7, Saccharomyces cerevisiae. J Biosci. Bioeng. 121, 247-252.

• Sato S., Nakazawa M., Kihara Y., Kubo Y., Sato Y., Kikuchi T., Nonaka A., Sasaki A., Iwashita J., Murata J., Hosaka M., Kobayashi M.; Partial inhibition of differentiation associated with elevated protein levels of pluripotency factors in mouse embryonic stem cells expressing exogenous EGAM1N homeoprotein. J. Biosci. Bioeng. 120, 562-569.

• Gomi H., Morikawa S., Shinmura N., Moki H., Yasui T., Tsukise A, Torii S., Watanabe T., Maeda Y., Hosaka M.; Expression of secretogranin III in chicken endocrine cells: its relevance to the secretory granule properties of peptide prohormone processing and bioactive amine content. J. Histochem Cytochem 63, 350-3566.

• Yoshihara T., Hosaka M., Terata M., Ichikawa K., Murayama S., Tanaka A., Mori M., Itabashi H., Takeuchi K., Tobita S.; Intracellular and in vivo oxygen sensing using phosphorescent Ir(III) complexes with a modified acetylacetonato ligand. Anal. Chem. 87, 2710-2717.

• Yoshihara T., Murayama S., Masuda T., Kikuchi T., Yoshida K., Hosaka M., Tobita S.; Mitochondria-targeted oxygen probes based on cationic iridium complexes with a 5-amino-1, 10-phenanthroline ligand. Journal of Photochemistry and Photobiology A: Chemistry 299 , 172–182.

• Horiuchi H., Hosaka M., Mashio H., Terata M., Ishida S., Kyusin S., Okutsu T., Takeuchi T., Hiratsuka H.; Silylation Improves the Photodynamic Activity of Tetraphenylporphyrin Derivatives In Vitro and In Vivo. Chemistry 20, 6054-6060.

• Watanabe, T., Bochimoto, H., Koga, D., Hosaka, M., Ushiki, T.; Functional Implications of the Golgi and Microtubular Network in Gonadotropes. Mol Cell Endocrinol. 385,　88-96.

• Sato S., Morita S., Iha M., Mori Y., Sugawara S., Kasuga K., Kojima I., Ozaki N., Muraguchi H., Okano K., Iwashita J., Murata J., Hosaka M., Kobayashi M.; Intact structure of EGAM1 homeoproteins and basic amino acid residues in the common homeodomain of EGAM1 and EGAM1C contribute to their nuclear localization in mouse embryonic stem cells. J. Biosci. Bioeng. 116, 141-146

• Tsuchiya, M., Manabe Y., Yamada, K., Furuichi, Y., Hosaka, M., Fujii, N.; Chronic exercise enhances insulin secretion ability of pancreatic islets without change in insulin content in non-diabetic rats. BBRC 430, 676-682

• Sun, M., Watanabe, T., Bochimoto, H., Sakai, Y., Torii, S., Takeuchi, T., Hosaka, M.; Multiple sorting systems for secretory granules ensure the regulated secretion of peotide hormones. Traffic 14, 205-218

• Watanabe, T., Sakai, Y., Koga, D., Bochimoto, H., Hira, Y., Hosaka, M., Ushiki, T.; A unique ball-shapeed Golgi apparatus in the rat pituitary ganadotrope: its functional implications in relation to the arrangement of microtuble network. J. Histochem. Cytochem. 60, 588-602

• Yoshihara, T., Yamaguchi, Y., Hosaka, M., Takeuchi, T., Tobita, S.: Ratiometric Molecular Sensor for Monitoring Oxygen Levels in Living Cells. Angew Chem Int Ed Engl. 51, 4148-4151

• Yoshihara. Y., Kobayashi, A., Oda, S., Hosaka, M., Takeuchi, T., Tobita, S.: Iridium Complex Probes for Monitoring of Cellular Oxygen Levels and Imaging of Hypoxic Tissues. Proc. SPIE 8233, 82330A1-82330A8

• Horiuchi, H., Kameya, T., Hosaka, M., Yoshimura, K., Kyushin, S., Matsumoto, H., Okutsu, T., Takeuchi, T., Hiratsuka, H. : Silylation Enhancement of Photodynamic Activity of Tetraphenylporphyrin Derivative. J. Photochem. Photobiol. 221, 98-104.

• Yamaguchi, R., Hosaka, M., Torii, S., Hou, N., Saito, N., Yoshimoto, Y., Imai., H., Takeuchi, T.: Cyclophilin C-associated protein regulation of phagocytic functions via NFAT activation in macrophages. Brain Res. 1397, 55-65.

• Saito, N., Takeuchi, T., Kawano, A., Hosaka, M., Hou, N., Torii, S.: Luminal Interaction of Phogrin with Carboxypeptidase E for Effective Targeting to Secretory Granules. Traffic 12, 499-506.

• Tsuchiya, M., Hosaka, M., Moriguchi, T., Zhang, S., Suda, M., Yokota-Hashimoto, H., Shinozuka, K., Takeuchi, T. (The first two authors contributed equally to this work.): Cholesterol Biosynthesis Pathway Intermediates and Inhibitors Regulate Glucose-stimulated Insulin Secretion and Secretory Granule Formation in Pancreatic beta-Cells. Endocrinology 151, 4705-4716

• Zhang, S., Hosaka, M., Yoshihara, T., Negishi, K., Iida, Y., Tobita, S., Takeuchi, T. (The first three authors contributed equally to this work.): Phosphorescent Light-emitting Iridium Complexes Serve as a Hypoxia-sensing Probe for Tumor Imaging in Living Animals. Cancer Reserch, 70,4490-4498.

• Hosaka M, Watanabe T: Secretogranin III: a bridge between core hormone aggregates and the secretory granule membrane. Endocrine J. 57, 275-286.

• Hotta, K., Hosaka, M., Tanabe, A., Takeuchi, T. (The first two authors contributed equally to this work.): Secretogranin II Binds to Secretogranin III and Forms Secretory Granules with Orexin, Neuropeptide Y and Proopiomelanocortin. J. Endocrinol. 202, 111-121

• Yoshihara, T., Karasawa, Y., Zhang, S., Hosaka, M., Takeuchi, T., Iida, Y., Endo, K., Imamura, T., Tobita, S.: In-Vivo Phosphorescence Imaging of Cancer Using Iridium Complexes. Proc. SPIE 7190, 71900X1-71900X9

• Han, L., Suda, M., Tsuzuki, K., Wang, R., Ohe, Y., Hirai, H., Watanabe, T., Takeuchi, T., Hosaka, M.: A large form of secretogranin III functions as a sorting receptor for chromogranin A aggregates in PC12 cells. Mol. Endocrinol. 22, 1935-1949

• Hou, N., Torii, S., Saito, N., Hosaka, M., Takeuchi, T.: Reactive Oxygen Species-Mediated Pancreatic beta-Cell Death Is Regulated by Interactions between Stress-Activated Protein Kinases, p38 and c-Jun N-Terminal Kinase, and Mitogen-Activated Protein Kinase Phosphatases. Endocrinology. 149, 1654-1665

• Takeuchi, T., Hosaka, M.: Sorting Mechanism of Peptide Hormones and Biogenesis Mechanism of Secretory Granules by Secretogranin III, a Cholesterol-Binding Protein, in Endocrine Cells. Curr. Diabetes Rev. 4, 31-38

• Kitahara, K., Sakai, Y., Hosaka, M., Hira, Y., Kakizaki, H., Watanabe, T.: Effects of a depot formulation of the GnRH agonist leuprorelin on the ultrastructure of male rat pituitary gonadotropes. Arch Histol Cytol. 70, 79-93.

• Hosaka, M., Watanabe, T., Yamauchi, Y., Sakai, Y., Suda, M., Mizutani, S., Takeuchi, T., Isobe, T., Izumi, T.: A subset of p23 localized on secretory granules in pancreatic beta-cells. J. Histochem. Cytochem. 55, 235-245.

• Wang, R., Hosaka, M., Han, L., Yokota-Hashimoto, H., Suda, M., Mitsushims, D., Torii, S., Takeuchi, T.: Molecular probes for sensing the cholesterol composition of subcellular organelle membranes. Biochim. Biophys. Acta. 1761, 1169-1181

• Hosaka, M., Watanabe, T., Sakai, Y., Kato, T., Takeuchi, T.: Interaction between secretogranin III and carboxypeptidase E facilitates prohormone sorting within secretory granules. J. Cell Science 118, 4785-4795.

• Sakai Y, Hosaka M, Hira Y, Watanabe T.: Addition of phosphotungstic acid to ethanol for dehydration improves both the ultrastructure and antigenicity of pituitary tissue embedded in LR White acrylic resin. Arch Histol Cytol. 68, 337-347.

• Aihara, M., Sugawara, K., Torii, S., Hosaka, M., Kurihara, H., Saito, N., Takeuchi, T.: Angiogenic Endothelium-specific Nestin Expression is enhanced by the First Intron of the Nestin Gene. Lab. Invest. 84, 1581-1592.

• Sakai, Y., Hosaka, M., Yoshinaga, A., Hira, Y., Harumi, T., Watanabe, T.: Immunocytochemical localization of secretogranin III in the endocrine pancreas of male rats. Arch Histol Cytol. 67, 57-64.

• Fujisawa, T., Kamimura, H., Hosaka, M., Torii, S., Izumi, T., Kuwano, H., Takeuchi, T.: Functional localization of proprotein-convertase furin and its substrate TGF in EGF receptor-expressing gastric chief cells. Growth Factors 22, 51-59.

• Hosaka, M., Suda, M., Sakai, Y., Izumi, T, Watanabe, T., Takeuchi, T.: Secretogranin III binds to cholesterol in the secretory granule membrane as an adapter for chromogranin A. J. Biol. Chem. 30, 3627-3634.

• Zhang, B., Hosaka, M., Sawada, Y., Torii, S., Mizutani, S., Ogata, M., Izumi, T., Takeuchi, T.: PTHrP induces insulin expression through activation of MAP kinase-specific phosphatase-1 that dephosphorylates c-jun N-terminal kinase in pancreatic beta-cells. Diabetes 52, 2720-2730.

• Sakai, Y., Hosaka, M., Hira, Y., Harumi, T., Ohsawa, Y., Wang, H., Takeuchi, T., Uchiyama, Y., Watanabe, T.: Immunocytochemical localization of secretogranin III in the anterior lobe of male rat pituitary glands. J. Histochem. Cytochem. 51, 227-238.

• Hosaka, M., Watanabe, T., Sakai, Y., Uchiyama, Y., Takeuchi, T.: Identification of a chromogranin A domain that mediates binding to secretogranin III and targeting to secretory granules in pituitary cells and pancreatic -Cells. Mol. Biol. Cell 13, 3388-3399.

• Yi, Z., Yokota, H., Torii, S., Aoki, T., Hosaka, M., Zhao, S., Takata, K., Takeuchi, T., Izumi, T.: The rab27a/granuphilin complex regulates the exocytosis of insulin-containing dense-core granules. Mol. Cell. Biol. 22, 1858-1867.

2000

• Zhang, W., Li, J.L., Hosaka, M., Janz, R., Shelton, J.M., Albright, G.M., Richardson, J.A., Südhof, T.C., Victor, R.G.: Cyclosporine A-induced hypertension involves synapsin in renal sensory nerve endings. Proc. Natl. Acad. Sci. 97, 9765-9770.

• Hosaka, M., Hammer, R.E., Südhof, T.C.: A phospho-switch controls the dynamic association of synapsins with synaptic vesicles. NEURON 24, 377-387.

• Dulubova, I., Sugita, S., Hill, S., Hosaka, M., Fernandez, I., Südhof, T.C., Rizo, J.: A conformational switch in syntaxin during exocytosis: role of munc18. EMBO J. 18, 4372-4382.

• Hosaka, M., Südhof, T.C.: Homo- and heterodimerization of synapsins. J. Biol. Chem. 274, 16747-16753.

1998

• Hosaka, M., Südhof, T.C.: Synapsin III, A novel synapsin with an usual regulation by Ca2+. J. Biol. Chem. 273, 13371-13374.

• Esser, L., Wang, C.-R., Hosaka, M., Smagulla, C.S., Südhof, T.C. Deisenhofer, J.: Synapsin I is structually Similar to ATP-utilizing enzymes. EMBO J. 17, 977-984.

• Hosaka, M., Südhof, T.C.: Synapsin I and II are ATP-binding proteins with differential Ca2+ regulation. J. Biol. Chem. 273, 1425-1429.

1996

• Hosaka, M., Toda, K., Takatsu, H., Watanabe. T., Banno, T., Ikehara, Y., Murakami, K., Nakayama, K.: Differential effects of Brefeldin A on intracellular localization of ADP-ribosylation factors type 1 to type 6 (ARF1-ARF6) cloned from mouse. J. Biochem. (Tokyo) 120, 813-819.

• Hosaka, M., Murakami, K., Nakayama,K.: PACE4A is a ubiquitous endoprotease that has similar but not identical substrate specificity to other Kex2-like processing endoproteases. Biomed. Res. 15, 383-390.

• Kako, K., Munekata, E., Hosaka, M., Murakami, K., Nakayama,K.: Cloning and Sequence Analysis of mouse cDNAs Encoding Preprotachykinin A and B. Biomed. Res. 14, 253-259.
• Nakagawa, T., Hosaka, M., Torii, S., Watanabe, T., Murakami, K., Nakayama, K.: Identification and Functional Expression of a New Member of the Mammalian Kex2-like Processing Endoprotease Family: Its Striking Structural Similarity to PACE4. J. Biochem. (Tokyo) 113, 132-135.

1992

• Nakayama, K., Watanabe, T., Nakagawa, T., Kim, W.S., Nagahama, M., Hosaka, M., Hatsuzawa, K., Kondoh-Hashiba, K., Murakami, K.: Consensus Sequence for Precursor Processing at Mono-arginil Sites; Evidence for the involvement of a Kex2-like endoprotease in precursor cleavages at both dibasic and mono-arginil sites. J. Biol. Chem. 267, 16335-16340.

• Nakayama, K., Kim, W.S., Torii, S., Hosaka, M., Nakagawa, T., Ikemizu, J., Baba, T., Murakami, K.: Identification of the fourth member of mammalian endoprotease family homologous to the yeast Kex2 protease. J. Biol. Chem. 267, 5897-5900.

• Hosaka, M., Nagahama, M., Kim, W.S., Watanabe, T., Hatsuzawa, K., Ikemizu, J., Murakami, K., Nakayama, K.: Arg-X-Lys/Arg-Arg motif as a signal for precursor cleavage catalyzed by furin within the constitutive secretory pathway. J. Biol. Chem. 266, 12127-12130.

• Nakayama, K., Hosaka, M., Hatsuzawa, K., Murakami, K.: Cloning functional expression of a novel endoprotease involved in prohormone processing at dibasic sites. J. Biochem. (Tokyo) 109, 803-806.

• Hatsuzawa, K., Hosaka, M., Nakagawa, T., Nagase, M., Showda, A., Murakami, K., Nakayama, K.: Structure and expression of mouse furin, a yeast-related protease; Lack of processing of coexpressed prorenin in GH4C1 cells. J. Biol. Chem. 265, 22075-22078.

Curriculum Vitae; Masahiro Hosaka
Research experiences and positions

1986-1990 B.S. Thesis. at University of Tsukuba
1990-1992 M.S. Thesis. at University of Tsukuba
1992-1995 Ph.D. Thesis. at University of Tsukuba
1995-1995 FOUNDATION FOR ADVANCEMENT OF INTERNATIONAL SCIENCE; research fellow at University of Tsukuba
(1985-1995: I have worked with Dr. Nakayama, now at Kyoto Univ.)

1995-1996: Howard Hughes Medical Institute research fellow at University of Texas Southwestern Medical Center at Dallas, Texas
1996-1998: Human Frontier Science Program postdoctoral fellow, at University of Texas Southwestern Medical Center at Dallas, Texas
1998-1999: Postdoctoral fellow, at University of Texas Southwestern Medical Center at Dallas, Texas
(1995-1999: I have worked for Dr. Südhof, the 2013 Nobel Prize in Physiology or Medicine laureates and now at Stanford Univ.)

1999-2004: Assistant Professor, at Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University, Japan
2004-2011: Associate Professor, at Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University, Japan
(1999-2008: I have worked with Dr. Takeuchi, retired on March 31, 2008.)

2011-present: Professor, at Laboratory of Molecular Life Sciences, Department of Biotechnology, Akita Prefectural University, Japan