The ultimate objective of the lab is to find a buried treasure from a mountain of biological data by bioinformatics. Successful prospectors instantly are hooked on natural beauty, even though the hitherto unknown gems may remain unappreciated by most people. If the discovered stones become a heritage of mankind, we the adventurers are willing to relinquish our legal claim but refuse to kick the habit.

 

Right now, our lab is carrying out research on intrinsically disordered regions of proteins, the regions that do not assume unique three-dimensional structures by themselves. As the amino acids of intrinsically disordered regions generally are mutated at high rates, they may provide the mechanism for rapid evolution of organisms. These flexible regions constitute as much as one third of human and other eukaryotic proteins and must have beneficial functions since cells expend as much as 80% of energy for protein synthesis. Although many intrinsically disordered regions are known to play crucial roles in protein functions including interactions with other proteins and nuclear molecules, others do not have known functions. We are committed to develop bioinformatics methods to identify the functions of more intrinsically disordered regions.

 

To this end, we are currently pursuing the following three lines of research:

(1)   The functions of intrinsically disordered regions in extracellular proteins, including those that undergo ectodomain shedding. Since intrinsically disordered regions are vulnerable to protease digestion in extracellular environment, they must be either protected and/or functional in short lifetime.

(2)   Translation rate differences between the structural and intrinsically disordered regions of proteins. As translation rate is likely to be optimized to synthesize functional proteins, the absence of folding in intrinsically disordered regions apparently indicates rapid translation. For some reason, however, this is not always the case. We aim to find the reasons of the unexpected finding.

(3)   The roles intrinsically disordered regions play in viral proteins. As viral proteins are under extreme pressure to efficiently spread the viral genome, the intrinsically disordered regions must play crucial roles.

 

Our research remains flexible to accommodate fast research development in intrinsically disordered regions. An interested reader is encouraged to contact the lab at

 

Curriculum vitae

EDUCATION    Ph.D. in Biophysics, Harvard University, Massachusetts, U.S.A.

Graduated in June 1987

B.A., Swarthmore College, Pennsylvania, U.S.A. Graduated with honors in May 1980. Majored in physics and minored in mathematics.

 

PROFESSIONAL EXPERIENCE

2012- Present     Department of Life Science and Informatics, Maebashi Institute of Technology, Maebashi, Japan

Professor

Carrying out research on intrinsically disordered regions of proteins. Supervising student projects. Teaching courses on bioinformatics, protein structure, computer programming, information network, and information security.

2007- 2012            DNA Data Bank of Japan, National Institute of Genetics, Mishima, Japan

Research fellow under Professor H. Sugawara

Designed and built databases for the Targeted Proteins Research Program, a national project in Japan to determine the three-dimensional structures of proteins that are medically, biologically, and industrially important. Proposed and built an automated functional annotation system. Carried out research on intrinsically disordered regions of proteins.

2000– 2007           DNA Data Bank of Japan, National Institute of Genetics, Mishima, Japan

Research fellow under Professor K. Nishikawa

Identified and characterized pseudogenes in Escherichia coli. Systematically analyzed relationships between human alternative splicing variants and protein structures. Developed a method to accurately identify horizontally transferred genes in bacteria and analyzed operon formation mechanisms.

1997- 2000            National Children’s Medical Research Center, Tokyo, Japan

Domestic Research Fellow under Professor G. Tsujimoto

Investigated the phospholipid transport pathway(s) in yeast cells and set up an in vitro expression cloning system

1996– 1997           Tokyo Institute of Technology, Yokohama, Japan

Assistant Professor in the Department of Life Science

Carried out research on the localization and function of a phospholipid-4-phosphate 5-kinase in yeast.

1993-1996             University of Tokyo, Tokyo, Japan

Research Fellow under Professor A. Nakano

Genetically investigated the mechanism(s) for the retention of membrane proteins in the endoplasmic reticulum in yeast

1987- 1993            Tonen Corporation (subsidiary of Exxon), Tokyo, Japan

Researcher at the Corporate Research Laboratory

Purified and cloned yeast protein disulfide isomerase and facilitated the folding of human serum albumin in yeast cells.

1986- 1987            City of Hope National Medical Center, Duarte, California, U.S.A.

Postdoctoral Fellow under Dr. R. R. Klevecz

Conducted research on the mammalian cell cycle using computer simulations and molecular biological techniques.

1980- 1986            Harvard University, Cambridge, Massachusetts, U.S.A.

Research Fellow at the Graduate School of Arts and Sciences under Professor J. W. Hastings

Analyzed the circadian control of cell division in a marine diatom using both experiments and computer simulations. Uncovered how and at which phase the cell cycle is regulated by the circadian clock and described growth in mathematical terms.

 

PUBLICATIONS

1.Sulzman, F.M., Gooch, V.D., Homma, K., and Hastings, J.W. (1982).  Cellular autonomy of the Gonyaulax circadian clock. Cell Biophys. 4:97-103.

2.Broda, H., Brugg, D., Homma, K., and Hastings, J.W. (1985). Circadian communication between unicells? Cell Biophys. 8:47-67.

3.Homma, K. and Hastings, J.W. (1988). Cell cycle synchronization of Gonyaulax polyedra by filtration: quantized generation times. J. Biological Rhythms 3:49-58.

4.Homma, K. and Hastings, J.W. (1989). The S phase is discrete and is controlled by the circadian clock in the marine dinoflagellate Gonyaulax polyedra. Exp. Cell Res. 182:635-644.

5.Homma, K. and Hastings, J.W. (1989). Cell growth kinetics, division asymmetry and volume control at division in the marine dinoflagellate Gonyaulax polyedra: a model of circadian clock control of the cell cycle. J. Cell Sci. 92:303-318.

6.Homma, K., Haas, E., and Hastings, J.W. (1990). Phase of the circadian clock is accurately transferred from mother to daughter cells in the dinoflagellate Gonyaulax polyedra. Cell Biophys. 16:85-97.

7. Homma, K. and Takahashi, N. (1992). [Modification enzymes of protein folding.] In [Protein VI: Synthesis and Translation (New Lecture Series in Biochemistry, vol. 1)], Tokyo Kagaku Dojin, pp. 331-341, Review in Japanese.

8. Yokozeki, T., Homma, K., Kuroda, S., Kikkawa, U., Ohno, S., Takahashi, M., Imahori, K., and Kanaho, Y. (1998). Phosphatidic acid-dependent phosyphorylation of a 29-kDa protein by protein kinase Cα in bovine brain cytosol. J. Neurochem. 71:410-417.

9. Homma, K., Terui, S., Minemura, M., Qadota, H., Anraku, Y., Kanaho, Y., and Ohya, Y. (1998). Phosyphaditylinositol-4-phosphate 5-kinase localized on the plasma membrane is essential for yeast cell morphogenesis. J. Biol. Chem. 273:15779-15786.

10. Homma, K., Yoshida, Y., and Nakano, A. (2000). Evidence for recycling of cytochrome P450-14DM from the cis-Golgi compartment to the endoplasmic reticulum (ER) upon saturation of the ER-retention mechanism. J. Biochem. 127:747-754.

11. Kawabata, T., Fukuchi, S., Homma, K., Ota, M., Araki, J., Ito, T., Ichiyoshi, N., and Nishikawa, K. (2002). GTOP: a database of protein structures predicted from genome sequences. Nucleic Acids Res. 30:294-298.

12. Homma, K. and Nishikawa, K. (2002). [Protein structure information provided by the GTOP database and its applications.] Tanpakushitsu Kakusan Koso 47(8 Suppl.):1076-1082. Review in Japanese.

13. Homma, K., Fukuchi, S., Kawabata, T., Ota, M., and Nishikawa, K. (2002). A systematic investigation identifies a significant number of probable pseudogenes in the Escherichia coli genome. Gene 294:25-33.

14. Imanishi, T., Itoh, T., Suzuki, Y., O'Donovan, C., Fukuchi, S., Koyanagi, K.O., Barrero, R.A., Tamura, T., Yamaguchi-Kabata, Y., Tanino, M., Yura, K., Miyazaki, S., Ikeo, K., Homma, K. and 144 others (2004). Integrative annotation of 21,037 human genes validated by full-length cDNA clones. PLoS Biol. 2:e162.

15. Homma, K., Kikuno R.F., Nagase, T., Ohara, O., and Nishikawa, K. (2004). Alternative splice variants encoding unstable protein domains exist in the human brain. J. Mol. Biol. 343:1207-1220.

16. Minezaki, Y., Homma, K., and Nishikawa, K. (2005). Genome-wide survey of transcription factors in prokaryotes reveals many bacteria-specific families not found in archaea. DNA Res. 12:269-280.

17. Homma, K. and Fukami, K. (2005). [Swiss-Prot: Protein information flow of a majestic river originating from the Swiss Alps.] In [Methods to Use Biological Databases: From Database Search to Bionformatics], Kaneshisa, M., Ogata, H., and Nishihara, S. editors, Gakushin Shuppan, pp. 77-87, Review in Japanese.

18. Fukuchi, S., Homma, K., Minezaki, Y., and Nishikawa, K. (2006). Intrinsically disordered loops inserted into the structural domains of human proteins. J Mol Biol. 355:845-857.

19. Minezaki, Y., Homma, K., Kinjo, A. R., and Nishikawa, K. (2006). Human transcription factors contain a high fraction of intrinsically disordered regions essential for transcriptional regulation. J. Mol. Biol. 359:1137-1149.

20. Homma, K., Fukuchi, S., Nakamura, Y., Gojobori, T., and Nishikawa, K. (2007). Gene cluster analysis method identifies horizontally transferred genes with high reliability and indicates that they provide the main mechanism of operon gain in 8 species of γ-Proteobacteria. Mol. Biol. Evol. 24:805-813.

21. Minezaki, Y., Homma, K., and Nishikawa, K. (2007). Intrinsically disordered regions of human plasma membrane proteins preferentially occur in the cytoplasmic segment. J. Mol. Biol. 368:902-913.

22. Fujiyama-Nakamura, S., Yoshikawa, H., Homma, K., Hayano, T., Tsujimura-Takahashi, T., Izumikawa, K., Ishikawa, H., Miyazawa, N., Yanagida, M., Miura, Y., Shinkawa, T., Yamauchi, Y., Isobe, T., and Takahashi, N. (2009). Parvulin (Par14), a peptidyl-prolyl cis-trans isomerase, is a novel rRNA processing factor that evolved in the metazoan lineage. Mol Cell Proteomics 8:1552-1565.

23. Fukuchi, S., Homma, K., Sakamoto, S., Sugawara, H., Tateno, Y., Gojobori, T., and Nishikawa, K. (2009). The GTOP database in 2009: updated content and novel features to expand and deepen insights into protein structures and functions. Nucleic Acids Res. 37: D333-D337.

24. Fukuchi, S., Homma K., Minezaki, Y., Gojobori, T., and Nishikawa, K. (2009). Development of an accurate classification system of proteins into structured and unstructured regions that uncovers novel structural domains: its application to human transcription factors. BMC Struct Biol. 9:26.

25. Nishikawa, I., Nakajima, Y., Ito, M., Fukuchi, S., Homma, K., and Nishikawa, K. (2010). Computational prediction of O-linked glycosylation sites that preferentially map on intrinsically disordered regions of extracellular proteins. Int. J. Mol. Sci. 11:4991-5008.

26. Homma, K., Suzuki, K., and Sugawara, H. (2011). The Autophagy Database: an all-inclusive information resource on autophagy that provides nourishment for research. Nucleic Acids Res. 39:D986-D990.

27. Homma K., Fukuchi S., Nishikawa K., Sakamoto S., and Sugawara H. (2012) Intrinsically disordered regions have specific functions in mitochondrial and nuclear proteins. Mol Biosyst. 8:247-255.

28. Hayashida K., Hara Y., Abe T., Yamasaki C., Toyoda A., Kosuge T., Suzuki Y., Sato Y., Kawashima S., Katayama T., Wakaguri H., Inoue N., Homma K., Tada-Umezaki M., Yagi Y., Fujii Y., Habara T., Kanehisa M., Watanabe H., Ito K., Gojobori T., Sugawara H., Imanishi T., Weir W., Gardner M., Pain A., Shiels B., Hattori M., Nene V., and Sugimoto C. (2012) Comparative genome analysis of three eukaryotic parasites with differing abilities to transform leukocytes reveals key mediators of Theileria-induced leukocyte transformation. MBio. 3:e00204-12

29. Gough C.A., Homma K., Yamaguchi-Kabata Y., Shimada M.K., Chakraborty R., Fujii Y., Iwama H., Minoshima S., Sakamoto S., Sato Y., Suzuki Y., Tada-Umezaki M., Nishikawa K., Imanishi T., and Gojobori T. (2012) Prediction of protein-destabilizing polymorphisms by manual curation with protein structure. PLoS One. 7:e50445.

30. Nishimura K., Ishikawa S., Matsunami E., Yamauchi J., Homma K., Faulkner C., Oparka K., Jisaka M., Nagaya T., Yokota K., and Nakagawa T. (2015) New Gateway-compatible vectors for a high-throughput protein-protein interaction analysis by a biomolecular fluorescence complementation (BiFC) assay in plants and their application to a plant clathrin structure analysis. Biosci. Biotechnol. Biochem. 79:1995-2006.

31. Homma K., Noguchi T., and Fukuchi S. (2016) Codon usage is less optimized in eukaryotic gene segments encoding intrinsically disordered regions than in those encoding structural domains. Nucl. Acids. Res. 44:10051-10061.

32. Miyamoto Y., Torii T., Kawahara K., Hasegawa K., Tanoue A., Seki Y., Morimoto T., Funakoshi-Tago M., Tamura H., Homma K., Yamamoto M., and Yamauchi J. (2017) Data on the effect of hypomyelinating leukodystrophy 6 (HLD6)-associated mutations on the TUBB4A properties. Data in Brief 11:284-289.

33. Shirakabe K., Omura T., Shibagaki Y., Mihara E., Homma K., Kato Y., Yoshimura A., Murakami Y., Takagi J., Hattori S., and Ogawa Y. (2017) Mechanistic insights into ectodomain shedding: susceptibility of CADM1 adhesion molecule is determined by alternative splicing and O-glycosylation. Sci. Rep. 7:46174.

34. Watanabe N., Itakaoka M., Seki Y., Morimoto T., Homma K., Miyamoto Y., and Yamauchi J. (2018) Dystonia-4 (DYT4)-associated TUBB4A mutants exhibit disorganized microtubule networks and inhibit neuronal process growth. Biochem. Biophys. Res. Commun. 495:346-352.

35. Matsumoto N., Kaneko M., Watanabe N., Itaoka M., Seki Y., Morimoto T., Torii T., Miyamoto Y., Homma K., Yamauchi J. (2018) Treacher Collins syndrome 3 (TCS3)-associated POLR1C mutants are localized in the lysosome and inhibits chondrogenic differentiation. Biochem. Biophys. Res. Commun. 499:78-85.

36. Urai Y., Yamawaki M., Watanabe N., Seki Y., Morimoto T., Tago K.,, Homma K., Sakagami H., Miyamoto Y., Yamauchi J. (2018) Pull down assay for GTP-bound form of Sar1a reveals its activation during morphological differentiation. Biochem. Biophys. Res. Commun. 503:2047-2053.

37. Hiraoka Y., Hattori K., Takeuchi Y., Yamawaki M., Watanabe N., Matsumoto N., Homma K., Miyamoto Y., Yamauchi J. (2018) Effects of HLD-associated POLR1C mutant proteins on cellular localization and differentiation. Mol. Genet. Metab. Rep. 17:80-82.

38. Homma K., Noguchi T., and Fukuchi S. (2018) Both intrinsically disordered regions and structural domains evolve rapidly in immune-related mammalian proteins. Int. J. Mol. Sci. 19:3860.

39. Tatsumi Y., Matsumoto N., Iibe N., Watanabe N., Torii T., Sango K., Homma K., Miyamoto Y., Sakagami H., and Yamauchi J. (2019) CMT type 2N disease-associated AARS mutant inhibits neurite growth that can be reversed by valproic acid. Neurosci. Res. 139:60-78.

40. Miyamoto, Y., Torii, T., Homma K., Oizumi, H., Ohbuchi, K., Mizoguchi, K., Takashima, S., and Yamauchi J. (2022) The adaptor SH2B1 and the phosphatase PTP4A1 regulate the phosphorylation of cytohesin-2 in myelinating Schwann cells in mice. Sci. Signal. 15: eabi 5276.